Late Injection Research Articles

Predictors of Injection Visit Adherence in Those Receiving Injectable Cabotegravir/Rilpivirine.

There is limited data evaluating potential predictors of adherence to injection visits and the impact of late injections on viral suppression in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for the treatment of HIV. A retrospective cohort study was conducted among adult people with HIV (PWH) receiving LAI CAB/RPV for at least 6 months between May 2021 and August 2023. Data collected included demographics, office visit no-shows one year prior to switching to LAI CAB/RPV, injection visit no-shows, injections outside the dosing window, and virologic outcomes. Cox-proportional hazards regression was performed to evaluate predictors of no-show to injection visits or late injections. Included were 287 PWH with a median follow up time (IQR) of 450 days (344-548 days). Younger age [HR 0.97 (95%CI 0.95-0.98)] and ≥ 1 office visit no-show in the year prior to switch to LAI CAB/RPV [HR 2.03 (1.32-3.12]) were associated with having a no-show to an injection visit (32.1%). Male sex assigned at birth [HR 9.18 (1.26-66.9)] with a trend towards younger age [HR 0.98 (0.95-1.0)] were associated with having a late injection (15.3%). There was no relationship between late injections and having a detectable viral load or virologic failure (n=3) after switch to LAI CAB/RPV. Having office visit no-shows prior to switching to LAI CAB/RPV was associated with missed injection visits, and younger age was associated with both missed injection visits and late injections. Resources to reduce and manage missed injection appointments need to be considered when implementing LAI CAB/RPV.

Research on jet ignition phases and control parameters in an active pre-chamber optical engine under ultra-lean combustion conditions

The active pre-chamber (APC) jet ignition system is one of the primary technologies for achieving ultra-lean combustion and high thermal efficiency in engines. The impact of the jet process within the engine, as well as its control parameters, on emission pollutants (particularly soot particles) remains unclear. This study focuses on examining the effects of various low-flow injection control strategies on engine combustion and emissions by using optical experiments and numerical simulations. It also explores the impact of different ignition advance angles (ignition timings) based on a short pre-chamber mixing interval to observe ignition combustion, flame propagation, and emission characteristics under ultra-lean conditions (λ = 2.0). The main conclusions are as follows. Appropriately increasing the injection mass can enhance engine load. However, further increases in injection mass significantly raise particulate emissions, resulting in an increase in particle number by up to more than 37-fold, especially for small particles in the 5–––10 nm size range. The chemical reaction between the luminous jet flame and the bright incandescent wake jet flame, as captured by high-speed photography, effectively characterizes the various stages of jet ignition. To reduce particulate matter emissions, it is crucial to avoid the foreseeable wake jet flame caused by the enrichment of the jet mixture in the pre-chamber. The low-flow injection timing should neither be too early nor close to the ignition spark timing. The early injection causes fuel to accumulate at the top of the pre-chamber, hindering the jet flame’s propagation into the main combustion chamber. Late low-flow injection leads to fuel enrichment, resulting in uneven mixing and poor atomization and diffusion due to short mixing times. Ignition after a short mixing time interval tends to increase knocking, resulting in intense combustion and an advanced phase, which slightly reduces load and combustion stability. Regarding the heat release ratio, the total heat release from the two combustion stages in the pre-chamber should ideally account for about 5–6 % of the heat release in the main chamber.

CFD unified approach under Eulerian-Lagrangian framework for methanol and gasoline direct injection sprays in evaporative and flash boiling conditions

Innovative synthetic fuels for advanced propulsion systems, such as methanol and ammonia, and synthetic blended fuels (E00, E10, and E30), known for their high volatility, are often injected directly into combustion chambers. It follows that Eulerian-Lagrangian spray models need to accurately capture the spray collapse as a consequence of flash boiling onset and be capable of proficiently handling the preferential evaporation of multi-component fuels in evaporative scenarios.So, we performed the assessment of an Eulerian-Lagrangian CFD code for simulating methanol and E00 gasoline blend sprays in both early and late injection conditions involving flash boiling conditions and preferential evaporation. The adoption of an effervescent breakup model and of a non-equilibrium phase transition model for the discrete phase allows the adoption of a setup that is almost completely free from specific constant tuning, especially for what concerns the breakup model. We validated the simulations using experimental PLV maps of methanol and E00 sprays issued from the ECN Spray M injector. The results highlight a significantly different morphology of the methanol spray compared to the E00 one under late injection conditions. Under stratified combustion, low-volatile fuels are likely to be ignited first, and the flame propagates toward the high-volatile fuels. The spray collapse was also correctly reproduced, inducing the presence of a low-pressure zone and modifying the spray morphology.

Hydrogen enrichment in methanol SI engine at varying injection timing during compression stroke

This study investigates the effect of hydrogen enrichment in a direct-injected methanol-fuelled SI engine, with combustion and emission performance analysed by varying the methanol injection timing from 150° to 60° CA bTDC. A three-dimensional computational fluid dynamic model of the hydrogen-enriched methanol engine was developed to predict the engine performance, in-cylinder, and emission characteristics. The numerical model was solved using three-dimensional Reynolds-Averaged Navier Stokes, the RNG k-epsilon model for turbulence, the O'Rourke and Amsden sub-model for heat transfer, the extended Zeldovich mechanism for nitric oxide emissions, and the Hiroyasu-NSC model for soot emissions. The results indicated that retarding the injection timing resulted in a decrease in the indicated specific CO and soot emissions along with a rise in the indicated specific NOx emissions. Furthermore, hydrogen enrichment with methanol enhanced the hydroxyl radical concentration, reduced the combustion duration, reduced also the indicated specific CO and soot emissions while increasing the indicated specific NOx emissions. The study indicates that hydrogen enrichment could extend the late injection timing limit of methanol by enhancing fuel-air mixing, which improves and controls the combustion process more effectively.

Investigation of fuel temperature and injection timing effects on ammonia direct injection in an optical engine

This work investigates the effects of fuel temperature and injection timing on ammonia direct injection in an optical engine using a multi-hole injector. Flash-boiling may occur over various engine-relevant conditions due to ammonia’s high vapor pressure. This phenomenon impacts spray characteristics and, in severe cases, facilitates cavitation inside the nozzle. Both fuel temperature and injection timing (i.e., ambient conditions during injection) impact the intensity of flash-boiling during fuel injection. Therefore, this work varies fuel temperature (from 320K to 388K) and injection timing (from −60CADaTDC (crank angle degrees after top dead center) to −6CADaTDC) to assess their impact on injection mass flux, discharge coefficients, and macroscopic spray characteristics using an ammonia injection pressure of 200bar. For this purpose, the injection mass is measured by analyzing exhaust gas compositions during engine operation with ammonia injections but without combustion. In addition, diffuse background illumination (DBI) images capture the liquid phase of the fuel spray to characterize spray behavior. The findings reveal that increasing fuel temperature decreases ammonia’s injection mass by up to 12.8% but has little impact on discharge coefficients for late injection timings and high in-cylinder pressures. However, discharge coefficients decrease by up to 17.4% (from 0.58 to 0.48) for early injection timings if fuel temperatures are high. The individual sprays of the 6-hole GDI injector may collapse into a uniform spray at high-density conditions without flash-boiling or under strongly flash-boiling conditions. The findings clarify the impact of ammonia’s high vapor pressure on injection mass and prove the relevance of different spray collapse mechanisms in ammonia direct injection engines.

Assessment of dual time point protocols to produce parametric Ki images in FDG PET/CT: A virtual clinical study.

This simulation study investigated the feasibility of generating Patlak Ki images using a dual time point (DTP-Ki) scan protocol involving two 3-min/bed routine static PET scans and, subsequently, assessed DTP-Ki performance for an optimal DTP scan time frame combination, against conventional Patlak Ki estimated from complete 0-93min dynamic PET data. Six realistic heterogeneous tumors of different characteristic spatiotemporal [18F]FDG uptake distributions for three noise levels commonly found in clinical studies and 20 noise realizations (N=360 samples) were produced by analytic simulations of the XCAT phantom. Subsequently, DTP-Ki images were generated by performing standard linear indirect Patlak analysis with t* -min (Patlakt* = 12) using a scaled population-based input function (sPBIF) model on 66 combinations of early and late 3-min/bed static whole-body PET reconstructed images. All DTP-Ki images were evaluated against respective DTP-Ki images estimated with Patlakt* = 12 and 0-93min individual input functions (iIFs) and against gold standard Ki images estimated with Patlakt* = 12, 0-93min iIFs and tissue time activity curves from all reconstructed WB passes 12-93min post injection. The optimal combination of early and late frames, in terms of attaining the highest correlation between DTP-Ki with sPBIF and gold standard Ki was also determined from a set of 66 different combinations of 2-min early and late frames. Moreover, the performance of DTP-Ki with sPBIF was compared against that of the retention index (RI) in terms of their correlation to the gold standard Ki. Finally, the feasibility and practicality of DTP protocol in the clinic were assessed through the analysis of nine patients. High correlations(>0.9) were observed between DTP-Ki values from sPBIF and those from iIFs for all evaluated DTP protocols while the mean AUC difference between sPBIF and iIFs was less than 10%. The percentage difference of mean values between DTP-Ki from sPBIF and from iIFs was less than 1%. DTP Ki from sPBIF exhibited significantly higher correlation with gold standard Ki, in contrast to RI, across all 66 DTP protocols (p<0.05 using the two-tailed t-test by Williams) with the highest correlation attained for the 50-53-min early + 90-93-min late scan time frames (optimal DTP protocol). Feasibility of generating Patlak Ki [18F] FDG images from an early and a late post injection 3-min/bed routine static scan using a population-based input function model was demonstrated and an optimal DTP scan protocol was determined. The results indicated high correlations between DTP-Ki and gold-standard Ki images that are significantly larger than those between RI and gold-standard Ki.

A comparative analysis of the performances of a syngas port injection plus gasoline direct injection combined-injection spark-ignition engine under lean-homogeneous charge and Lean-Stratified Charge modes

This study conducts a comparative analysis of the performances of a syngas port injection plus gasoline direct injection combined-injection spark-ignition engine operating in Lean-Homogeneous Charge (LHC) and Lean-Stratified Charge (LSC) modes. Results demonstrate that adjusting direct injection timing achieves LHC with early intake stroke injection and LSC with late compression stroke injection. Regarding mixture charge, increasing excess air ratio (λ) or syngas injection proportion (SIP) in LHC mode improves mixture homogeneity, while a higher SIP in LSC mode enhances mixture distribution for ignition. Concerning combustion characteristics, both modes benefit from lower λ and higher SIP with increased peak cylinder pressure, heat release rate, flame speed, and in-cylinder temperature. A higher λ extends CA0-10 and CA10-90, while a higher SIP shortens these durations. Regarding emissions, a higher λ positively affect HC, CO, and NOx emissions, whereas a higher SIP reduces HC, CO and soot but increases NOx emissions. The comparison between LHC and LSC highlights the superior combustion efficiency of LSC, whereas LHC excels in emission control.

Controls on the genesis of a giant sand injection complex; insights into the Paleogene evolution of the stress of northern and central California

Giant sand injection complexes and localized swarms of sandstone intrusions are common in Upper Cretaceous to Miocene sedimentary successions of central and northern California within a distance of less than 100 km from the Pacific margin of the North America plate. One of the best preserved and extensively exposed injection complexes is the late Eocene Tumey Giant Injection Complex. The emplacement of sand injectites was driven by overpressure generated by thermal diagenesis of biosiliceous and smectite-rich mudstone host-rocks. The orientation and size distribution of sandstone intrusions was controlled by stress in which σ 1 and σ 3 were horizontal and, respectively, parallel and perpendicular to the present trace of the San Andreas Fault, and σ 2 was vertical. A strike-slip tectonic regime is inferred. Our analysis documents margin-orthogonal extension and provides support for a late Eocene phase of increase of strain, and possibly active slip, along a syn-subduction strike-slip fault zone. Comparison with other injection complexes in the region indicates that the near-field maximum principal stress rotated through time, from normal to parallel with respect to the plate margin, probably in relation to variations of the relative motion vector of the converging plates.

Chemical reaction network analysis on N2O emissions control strategies of ammonia/ methanol Co-combustion

As a kind of substitute fuel of hydrocarbon fuel, ammonia has gained increasing attention for its potential to reduce carbon emissions. Blending with carbon-neutral methanol is expected to deal with the slow flame speed of ammonia. Nevertheless, the emission of N2O, a byproduct of ammonia combustion, would undermine the carbon reduction benefits due to its high global warming potential. This study employed Chemkin to construct a Chemical Reaction Network (CRN) model to analyze the reaction kinetics of ammonia combustion when blended with a small amount of methanol. It finds that the increases in the methanol blending ratio, pressure, and temperature can reduce greenhouse gas emissions effectively. Further analysis indicates that pressure and temperature have distinct effects on the emission mechanisms of N2O and NO. Increasing the combustion pressure weakens the chain reactions, thereby reducing the formation of both NO and N2O; the increase in initial temperature raises NO emissions, but also promotes the decomposition of N2O due to the abundance of H in the post-combustion phase. Optimizing post-combustion efficiency and controlling the formation of NO are crucial for N2O emission control. Thus, a staged methanol injection strategy is proposed, where early injection reduces NO emissions and late injection facilitates the decomposition of N2O.

Effects of Various Compression Ratios on a Direct Injection Spark Ignition Hydrogen-Fueled Engine in a Single-Cylinder Engine

AbstractThe effects of compression ratio and injection timing on a direct injection spark ignition hydrogen engine under various excessive air ratios were analyzed using a 0.4-L single-cylinder engine in this study. The engine speed was set to 1500 rpm, and the excessive air ratio was changed by controlling the amount of injected hydrogen under wide-open throttle conditions. The compression ratio was changed from 10, 12, and 14 and the injection timing was varied from BTDC 200, 160, 120°CA. The results revealed that for a compression ratio 14 at a rich limit, late injection timing reduced knocking incidence by taking advantage of stratified mixtures combustion and increased indicated thermal efficiency by reducing combustion loss while producing lower NOx emissions. For compression ratio 14 at an excessive air ratio of 2.2, late injection timing increased indicated thermal efficiency by reducing both combustion and heat losses, achieving the higher indicated thermal efficiency of 42.3%. Although NOx emissions increased with the injection timing retardation, NOx emissions decreased to under 1 g/kWh under excessive air ratios above 2.5 conditions at all injection timings.

Investigating the potential of a higher reactivity fuel to achieve faster heat-up of aftertreatment systems

Shortening the aftertreatment system heat-up period will be crucial to meet upcoming emissions regulations, which mandate significant reductions in tail-pipe emissions for on-road heavy-duty vehicles. This work studies the impact of increasing fuel reactivity on the combustion of post injections during the expansion stroke. The work demonstrates an operating strategy using a blend of di-butyl ether (a potential low-carbon biofuel component) and #2 diesel that achieves higher exhaust enthalpy, while maintaining similar engine-out emissions (NOx and combustion efficiency) in comparison to the baseline #2 diesel fuel (cetane number 41). On average, a 12% increase in exhaust enthalpy was observed for the blend (cetane number 60) relative to the baseline fuel. The ability to operate the higher reactivity fuel at a more retarded post-injection timing, where combustion with #2 diesel was found to be more unstable, and less complete was key to achieving higher exhaust enthalpy. However, a small fuel penalty (∼ 3%–5%) was also associated with the higher reactivity fuel with this operating strategy. The formation of fuel lean regions, due to the long ignition delays at late injection conditions, was predicted to be the leading contributor to the increased emissions of products of partial combustion. Chemical kinetic simulations using surrogates for the fuels used in the experiments, demonstrated the ability of a higher cetane fuel to outperform the baseline fuel under fuel lean conditions with equivalence ratios less than 0.7.

Identifying Implementation Determinants and Strategies for Long-Acting Injectable Cabotegravir-Rilpivirine in People With HIV Who Are Virally Unsuppressed.

Early evidence suggests long-acting injectable cabotegravir and rilpivirine (LA-CAB/RPV) may be beneficial for people with HIV (PWH) who are unable to attain viral suppression (VS) on oral therapy. Limited guidance exists on implementation strategies for this population. Ward 86, a clinic serving publicly insured PWH in San Francisco. We describe multilevel determinants of and strategies for LA-CAB/RPV implementation for PWH without VS, using the Consolidated Framework for Implementation Research. To assess patient and provider-level determinants, we drew on pre-implementation qualitative data. To assess inner and outer context determinants, we undertook a structured mapping process. Key patient-level determinants included perceived ability to adhere to injections despite oral adherence difficulties and care engagement challenges posed by unmet subsistence needs; strategies to address these determinants included a direct-to-inject approach, small financial incentives, and designated drop-in days. Provider-level determinants included lack of time to obtain LA-CAB/RPV, assess injection response, and follow-up late injections; strategies included centralizing eligibility review with the clinic pharmacist, a pharmacy technician to handle procurement and monitoring, regular multidisciplinary review of patients, and development of a clinic protocol. Ward 86 did not experience many outer context barriers because of rapid and unconstrained inclusion of LA-CAB/RPV on local formularies and ability of its affiliated hospital pharmacy to stock the medication. Multilevel strategies to support LA-CAB/RPV implementation for PWH without VS are required, which may necessitate additional resources in some settings to implement safely and effectively. Advocacy to eliminate outer-context barriers, including prior authorizations and specialty pharmacy restrictions, is needed.

Sequelae Treatment Needs Following Peripheral Facial Palsy: Retrospective Analysis of 525 Patients.

This study uses retrospective longitudinal data from a large unselected cohort of patients with peripheral facial paralysis to determine the prevalence and patient characteristic predictors of sequelae receiving intervention. Retrospective case review. Karolinska University Hospital in Stockholm Sweden serves as the only tertiary facial palsy center in the region. Here, patients are diagnosed, are followed up, and undergo all major interventions. All adult patients presenting with peripheral facial palsy due to idiopathic, zoster, or Borrelia origin at Karolinska, January 1, 2010 to December 31, 2011 with follow-up until December 2022. Patient charts were studied to identify patient characteristics, etiology, initial treatment, severity of palsy, and treatments targeting sequelae. Types of initial and late treatments were noted. Sunnybrook and/or House-Brackmann scales were used for palsy grading. Five hundred twenty-five patients were included. Thirty-three patients (6.3%) received botulinum toxin injections and/or surgical treatment. In this subgroup, 67% received corticosteroids compared to 85% of all patients ( p = 0.005), cardiovascular disease prevalence was higher (23 and 42%, respectively, p = 0.009). For 81 patients (15%), follow-up was discontinued although the last measurement was Sunnybrook less than 70 or House-Brackmann 3 to 6. Of patients with peripheral facial palsy, 6.3% underwent injections and/or surgical treatment within 12 years. However, due to a rather large proportion not presenting for follow-up, this might be an underestimation. Patients receiving late injections and/or surgical treatment had more comorbidities and received corticosteroid treatment to a significantly lower extent in the acute phase of disease.

Effects of biodiesel injector configuration and its injection timing on performance, combustion and emissions characteristics of liquid ammonia dual direct injection engine

Ammonia is a promising carbon-neutral fuel that can be stored and transported in liquid form, offering a viable alternative to diesel fuel. In addition, it can be used directly in diesel engine in its liquid form in dual fuel mode. Hence, a single-cylinder diesel engine was modified to implement two common rail (CR) injection systems, allowing the direct injection of liquid ammonia with biodiesel. As biodiesel was used for a pilot fuel with lower injected mass, this study aims to investigate the influence of the number of nozzles in the biodiesel injector on the performance, combustion, and emissions characteristics of the liquid ammonia-biodiesel dual direct injection engine. Therefore, the number of holes in the CR injector was closed in various configurations to improve injection parameters. Furthermore, various biodiesel start of injection (SOI) timings were tested, ranging from −24 to −14 CAD, while the SOI of ammonia was kept at −10 CAD with an ammonia mass ratio of 67.2%. The results showed that welding three nozzles from the original six-nozzle injector resulted in a remarkable 29.2% reduction in NH3 and CO emissions. Furthermore, the highest indicated thermal efficiency of 39.7% was obtained for the injector with 3b nozzles. Additionally, late injection of both fuels led to an increase in particulate matter emissions, from 10.5 to 15.2 mg/m3, due to the formation of fuel-rich zones at high temperatures. However, it reduced NOx and CO emissions by 1.4 and 4.4 g/kWh, respectively, compared to the early SOI of biodiesel. Moreover, the lowest N2O emission was measured at 115.0 ppm in the earliest SOI of biodiesel at −24 CAD.

ImmunoPET imaging of TIGIT in the glioma microenvironment

Glioblastoma (GBM) is the most common primary malignant brain tumor. Currently, there are few effective treatment options for GBM beyond surgery and chemo-radiation, and even with these interventions, median patient survival remains poor. While immune checkpoint inhibitors (ICIs) have demonstrated therapeutic efficacy against non-central nervous system cancers, ICI trials for GBM have typically had poor outcomes. TIGIT is an immune checkpoint receptor that is expressed on activated T-cells and has a role in the suppression of T-cell and Natural Killer (NK) cell function. As TIGIT expression is reported as both prognostic and a biomarker for anti-TIGIT therapy, we constructed a molecular imaging agent, [89Zr]Zr-DFO-anti-TIGIT (89Zr-αTIGIT), to visualize TIGIT in preclinical GBM by immunoPET imaging. PET imaging and biodistribution analysis of 89Zr-αTIGIT demonstrated uptake in the tumor microenvironment of GBM-bearing mice. Blocking antibody and irrelevant antibody tracer studies demonstrated specificity of 89Zr-αTIGIT with significance at a late time point post-tracer injection. However, the magnitude of 89Zr-αTIGIT uptake in tumor, relative to the IgG tracer was minimal. These findings highlight the features and limitations of using 89Zr-αTIGIT to visualize TIGIT in the GBM microenvironment.

Script late injection: a framework to introduce JavaScript into web pages

Script injection is one type of fault present in web, which mostly utilizes user data to execute code without applying any type of filters. Script injection can impact both client and server making exposing them to vulnerabilities. Security and related products may need to execute logic on the client-side generally in a browser. In order to achieve this, proxy servers inject appropriate JavaScript code into the responses they proxy. Typically, the injection point is at the end of the body element. The framework introduced in this paper rather uses a stack-based approach to determine the injection point in the web page. Ten kilobytes from the end of a web page are given as a string input to the framework, after tokenization and construction of the vector of tokens. A stack is used to determine the injection point. Along with the position of the injection point, a warning flag is also estimated indicating the correctness of the injection point. Different types of web pages were considered for running the unit tests and fuzzy tests on the framework. These classes of pages are determined by crawling most used web pages. The injected scripts are executed once the body content is completely loaded. Hence, it can retrieve maximum information without affecting end-user performance. It also does the job at a low cost.

Effects of PODE substitution rate and fuel injection timing on combustion, emission characteristic and energy balance in PODE-gasoline dual direct-injection engine

Dual direct injection (DDI) mode allows two kinds of different reactivity fuels to be flexibly injected into the cylinders and offers lower pressure rise rate (PRR), CO and HC emissions than Reactivity Controlled Compression Ignition (RCCI) mode. Thus, a single-cylinder engine was modified to adopt two direct-injection systems to inject PODE and gasoline respectively in this paper. Due to high oxygen content and high cetane number, PODE was selected as a high reactivity fuel to replace diesel in the experiments. The effects of different PODE substitution rates(PSR), PODE injection timing(injP) and gasoline injection timing(injG) on the combustion, emission characteristics and energy balance were studied. The results concluded the using PODE-gasoline mode could increase the indicated thermal efficiency(ITE) and reduce exhaust losses compared to the diesel-gasoline mode. As PSR increased, it led to the increased ITE and effective power, decreased CO, HC emissions. Compared to the PODE late injection mode, the effective power and ITE were higher, and CO, HC emissions were lower in the PODE early injection mode. The coefficient of variation of IMEP(COVIMEP) for the DDI combustion was also in an acceptable range. Furthermore, an early injG could lead to higher ITE, lower COVIMEP, CO and HC.

6-month Formulations of Androgen Deprivation Therapy for Advanced Prostate Cancer: Effectiveness and Rationale for Extended Dosing

Background: Luteinizing hormone-releasing hormone (LHRH) agonists and GnRH antagonists are the most widely used androgen deprivation therapy to achieve castration levels of serum testosterone (T). Adherence to dosing schedules is important to avoid treatment failure. A recent analysis found a high non-adherence rate of 84% for LHRH agonist injections based on dosing schedules used in pivotal trials. Method: Narrative review of LHRH therapy and evaluation of which offers optimal efficacy, safety, and practicality. Results: 6-month LHRH agonist formulations require fewer appointments for injections than shorter-acting formulations. Therefore, the frequency of late/missed doses and overall non-adherence may be reduced compared to options requiring frequent dosing (e.g., oral therapies and shorter-acting injections). This flexibility may be preferable for patients who live in multiple locations throughout the year, live long distances from clinics, and/or lack access to reliable transportation. 6-month formulations may also have cost benefits compared to shorter-acting doses. Despite similar levels of T suppression during the labeled dosing period, individual 6-month LHRH agonist formulations appear to have unique profiles, e.g., 6-month subcutaneous leuprolide acetate (LA) results in lower T escape rates compared to 6-month intramuscular LA, if dosing is late. Conclusion: The efficacy and practicality offered by 6-month LHRH formulations suggest these could reduce opportunities for late injections by requiring fewer office visits and provide greater confidence that efficacy will be maintained should there be extenuating circumstances leading to delays in therapy administration, as experienced during the recent pandemic.

Stabilization and evolution of the Brazilian subcontinental lithospheric mantle: Insights from garnet xenocrysts and peridotite xenoliths of Três Ranchos kimberlite (APIP, Brazil)

The thermal structure and chemical composition of the subcontinental lithospheric mantle beneath the Alto Paranaíba Igneous Province defined by the major and trace element compositions of garnet and clinopyroxene xenocrysts and mantle peridotite xenoliths entrained in the Cretaceous Três Ranchos kimberlite. Estimated temperatures and pressures indicate a typical cratonic geotherm, with a surface heat flow of ∼ 40 mW/m2 slightly hotter than that at the São Francisco Craton margin (35–36 mW/m2), suggesting lateral heterogeneities in the geothermal gradients. A deep mantle portion (160 km) is recorded by a lherzolite xenolith (5 GPa and 1200 °C). This portion has undergone pervasive interstitial melt percolation of an ultra-alkaline silicate melt and late injection of small silicate melt fractions such as the host carbonated kimberlite. This pervasive migration extended into shallower SCLM sectors at 124–100 km (3.9–3.1 GPa and ∼ 940–810 °C) as evidenced by metasomatized (±phlogopite) peridotite identified by sinusoidal REE garnet compositions. This portion is apparently intercalated at 120–110 km depth (3.7–3.3 GPa and ∼ 850 °C) with strongly depleted peridotites showing garnet and clinopyroxene compositions extremely impoverished in moderately incompatible elements, as a result of extreme ancient, melt extraction. Atop the metasomatized and depleted peridotites, at 100 km depth, a layer of fertile lherzolite is identified by garnet xenocrysts, with 'normal', HREE-enriched, steadily fractionated LREE-depleted patterns. Combining our data with those of the Osvaldo França SCLM points to the occurrence of a deeper sector (>100 km depth beneath Trȇs Ranchos) originally formed by extremely depleted peridotites, successively metasomatized by ultra-alkaline melts; and a shallower sector of the São Francisco craton composed of fertile lherzolites unrelated to ultra-alkaline magmatism. Similar fertile lherzolites are found in the uppermost sectors of the Siberian and Kaapval SCLM, suggesting that they may be a ubiquitous, primary feature, possibly related to the stabilization of the Archean cratons.

Split injection strategies for a high-pressure hydrogen direct injection in a small-bore dual-fuel diesel engine

Hydrogen-diesel dual direct-injection (H2DDI) engines present a promising pathway towards cleaner and more efficient transportation. In this study, hydrogen split injection strategies were explored in an automotive-size single-cylinder compression ignition (CI) engine, with a focus on varying the injection timings and energy fractions. The engine was operated at an intermediate load with fixed combustion phasing through adjustments of pilot diesel injection timing. An energy substitution principle guided the variation in energy fraction between the two hydrogen injections and then diesel injection while keeping the total energy input constant. The findings demonstrate that early first hydrogen injection timings lead to characteristics indicative of premixed combustion, reflecting a high homogeneity of the hydrogen-air mixture. In contrast, hydrogen stratification levels were predominantly influenced by later second injection timings, with mixing-controlled combustion behaviour apparent for very late injections near top dead centre or when the second hydrogen injection held high energy fractions, which led to decreased nitrogen oxides (NOx: NO and NO2) emissions. The carbon dioxide (CO2) emissions did not show high sensitivity to the hydrogen split injection strategies, exhibiting about 77 % reduction compared to the diesel baseline due primarily to increased hydrogen energy fraction of up to 90 %.