Gravity-driven controls on fluid and carbonate precipitation distributions in fractures.

Many challenges related to carbon-dioxide ([Formula: see text]) sequestration in subsurface rock are linked to the injection of fluids through induced or existing fracture networks and how these fluids are altered through geochemical interactions. Here, we demonstrate that fluid mixing and carbonate mineral distributions in fractures are controlled by gravity-driven chemical dynamics. Using optical imaging and numerical simulations, we show that a density contrast between two miscible fluids causes the formation of a low-density fluid runlet that increases in areal extent as the fracture inclination decreases from 90[Formula: see text] (vertical fracture plane) to 30[Formula: see text]. The runlet is sustained over time and the stability of the runlet is controlled by the gravity-driven formation of 3D vortices that arise in a laminar flow regime. When homogeneous precipitation was induced, calcium carbonate covered the entire surface for horizontal fractures (0[Formula: see text]). However, for fracture inclinations greater than 10[Formula: see text], the runlet formation limited the areal extent of the precipitation to less than 15% of the fracture surface. These insights suggest that the ability to sequester [Formula: see text] through mineralization along fractures will depend on the fracture orientation relative to gravity, with horizontal fractures more likely to seal uniformly.

Feasibility and safety of same-day discharge following single-port robotic-assisted laparoscopic prostatectomy.

PURPOSE: The standard discharge pathway following robotic-assisted laparoscopic prostatectomy (RALP) involves overnight hospital admission. Models for same-day discharge (SDD) have been explored for multiport RALP, however, less is known regarding SDD for single-port RALP, especially in terms of patient experience. METHODS: Patient enrollment, based on preoperative determination of potential SDD eligibility, commenced March 2020 and ended March 2021. Day-of-surgery criteria were utilized to determine which enrolled patients underwent SDD. Differences in preoperative characteristics and perioperative outcomes between patients undergoing SDD and patients undergoing standard discharge were evaluated. A prospectively administered questionnaire was designed to characterize patient-centered factors informing SDD perception. RESULTS: Fifteen patients underwent SDD and 36 underwent standard discharge. Overall mean ± SD age and BMI were 63.6 ± 7.0 years and 29.7 ± 4.4 kg/m2, respectively. Mean operative time was shorter in the SDD cohort than the standard discharge cohort (188 min vs 217 min, p = 0.011). A higher proportion of cases that underwent SDD were performed using the Retzius-sparing approach, 80% (12/15) vs 33% (12/36) in the standard discharge cohort (p = 0.005). Rates of 90 day complication (p = 0.343), 90 day readmission (p = 0.144), and 90 day emergency department visits (p = 0.343) rates were all not significantly different between cohorts. Of questionnaire respondents undergoing standard discharge, 32% (8/25) cited pain as a reason for not undergoing SDD. CONCLUSIONS: With comparable outcomes to the standard discharge pathway, SDD is safe and effective in single-port RALP. Post-operative pain and perceptions of distance are implicated as patient-centered barriers to SDD; proactive pain management and patient education strategies may facilitate SDD.

Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study.

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23-7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03-8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17-37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15-12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.

Fluid Behavior in Nanoporous Silica.

We investigate dynamics of water (H2O) and methanol (CH3OH and CH3OD) inside mesoporous silica materials with pore diameters of 4.0, 2.5, and 1.5 nm using low-field (LF) nuclear magnetic resonance (NMR) relaxometry. Experiments were conducted to test the effects of pore size, pore volume, type of fluid, fluid/solid ratio, and temperature on fluid dynamics. Longitudinal relaxation times (T1) and transverse relaxation times (T2) were obtained for the above systems. We observe an increasing deviation in confined fluid behavior compared to that of bulk fluid with decreasing fluid-to-solid ratio. Our results show that the surface area-to-volume ratio is a critical parameter compared to pore diameter in the relaxation dynamics of confined water. An increase in temperature for the range between 25 and 50°C studied did not influence T2 times of confined water significantly. However, when the temperature was increased, T1 times of water confined in both silica-2.5 nm and silica-1.5 nm increased, while those of water in silica-4.0 nm did not change. Reductions in both T1 and T2 values as a function of fluid-to-solid ratio were independent of confined fluid species studied here. The parameter T1/T2 indicates that H2O interacts more strongly with the pore walls of silica-4.0 nm than CH3OH and CH3OD.

Members of Marinobacter and Arcobacter Influence System Biogeochemistry During Early Production of Hydraulically Fractured Natural Gas Wells in the Appalachian Basin.

Hydraulic fracturing is the prevailing method for enhancing recovery of hydrocarbon resources from unconventional shale formations, yet little is understood regarding the microbial impact on biogeochemical cycling in natural-gas wells. Although the metabolisms of certain fermentative bacteria and methanogenic archaea that dominate in later produced fluids have been well studied, few details have been reported on microorganisms prevelant during the early flowback period, when oxygen and other surface-derived oxyanions and nutrients become depleted. Here, we report the isolation, genomic and phenotypic characterization of Marinobacter and Arcobacter bacterial species from natural-gas wells in the Utica-Point Pleasant and Marcellus Formations coupled to supporting geochemical and metagenomic analyses of produced fluid samples. These unconventional hydrocarbon system-derived Marinobacter sp. are capable of utilizing a diversity of organic carbon sources including aliphatic and aromatic hydrocarbons, amino acids, and carboxylic acids. Marinobacter and Arcobacter can metabolize organic nitrogen sources and have the capacity for denitrification and dissimilatory nitrate reduction to ammonia (DNRA) respectively; with DNRA and ammonification processes partially explaining high concentrations of ammonia measured in produced fluids. Arcobacter is capable of chemosynthetic sulfur oxidation, which could fuel metabolic processes for other heterotrophic, fermentative, or sulfate-reducing community members. Our analysis revealed mechanisms for growth of these taxa across a broad range of salinities (up to 15% salt), which explains their enrichment during early natural-gas production. These results demonstrate the prevalence of Marinobacter and Arcobacter during a key maturation phase of hydraulically fractured natural-gas wells, and highlight the significant role these genera play in biogeochemical cycling for this economically important energy system.

Altered homeostatic regulation of innate and adaptive immunity in lower gastrointestinal tract GVHD pathogenesis.

Lower gastrointestinal (GI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic stem cell transplantation. Recent data indicate that lower GI tract GVHD is a complicated process mediated by donor/host antigenic disparities. This process is exacerbated by significant changes to the microbiome, and innate and adaptive immune responses that are critical to the induction of disease, persistence of inflammation, and a lack of response to therapy. Here, we discuss new insights into the biology of lower GI tract GVHD and focus on intrinsic pathways and regulatory mechanisms crucial to normal intestinal function. We then describe multiple instances in which these homeostatic mechanisms are altered by donor T cells or conditioning therapy, resulting in exacerbation of GVHD. We also discuss data suggesting that some of these mechanisms produce biomarkers that could be informative as to the severity of GVHD and its response to therapy. Finally, novel therapies that might restore homeostasis in the GI tract during GVHD are highlighted.

Phase I/II Trial of Dose-Escalated Busulfan Delivered by Prolonged Continuous Infusion in Allogeneic Transplant Patients.

Intensive chemotherapy or chemotherapy plus irradiation and allogeneic stem cell transplantation can be curative for patients with hematologic diseases. Reduced-intensity transplants can also achieve cure and result in less treatment-related mortality but higher relapse rates. Thus, optimizing the conditioning regimens used in allogeneic transplantation remains an important goal. We conducted a phase I/II trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a continuous infusion of busulfan over 90 hours in conjunction with fludarabine followed by allogeneic related or unrelated donor transplant. Fifty-four patients with advanced hematologic malignancies were enrolled on this study. The MTD was identified as a 24-hour area under the curve (AUC) of approximately 7095 µM/min, which represents a 43% increase over the standard total daily AUC dose of 4800 µM/min given by intermittent schedules. DLTs at doses over 8000 µM/min were identified by a desquamative skin rash and mucositis. No dose-related increase in hepatic, pulmonary, or other organ toxicities were seen, whereas efficacy appeared to be improved at higher dose levels. Continuous-infusion busulfan with intermittent fludarabine provides an alternative treatment strategy that is generally well tolerated and permits an increase in total busulfan dose with encouraging efficacy. (NCI study no. NCT00448357.).