Injection Schedule Research Articles

Clonidine for pain-related distress in Aboriginal children on a penicillin regimen to prevent recurrence of rheumatic fever.

Indigenous children and adolescents in Australia and globally bear the burden of acute rheumatic fever (ARF). It has been virtually eliminated in well-resourced, developed settings. ARF is an autoimmune response to infection with group A Streptococcus. The mainstay of management is long-acting intramuscular penicillin injections to prevent recurrence of ARF and development of rheumatic heart disease (RHD), comprising valvular pathology and attendant complications. In Australia, penicillin injections are currently prescribed every 28 days for 5-10 years after diagnosis of ARF, depending on cardiac involvement. Adherence to this regimen reduces ARF recurrences and RHD progression. 'Days at risk' of ARF recurrence are calculated as the number of days after day 28 that an injection is not received. Adherence to the injection schedule has been reported as difficult in most global locations due to the painful nature of the injections, the long timeframes of the prescription, young age of patients, access problems and costs in some locations. The newly updated Australian guideline on the prevention, diagnosis and management of ARF and RHD has a chapter dedicated to secondary prophylaxis. This chapter takes into account cultural considerations and advises on ways to minimise pain and distress of injections in children such as pain gate strategies, distraction techniques and concurrent injection of local anaesthetic. Some children continue to find the injection regimen traumatising despite strategies to reduce pain and fear. Clinicians providing the injections to children also find the injecting episodes distressing if pain is not effectively minimised. An Aboriginal Community Controlled Health Service in a remote setting in northern Australia addressed the issue of severe trauma of injection episodes experienced by an Aboriginal boy aged 7 years. Usual strategies were not effective, so advice was sought from an expert anaesthetist at a tertiary hospital. As a result, oral clonidine 3 µg/kg was trialled 45 minutes prior to the penicillin injection. Procedural coaching and monitoring protocols specific to administration of clonidine in children under their care were created by the health service. The initial dose of clonidine was delivered with the child as an inpatient. Clonidine was successful in reducing pain related distress and facilitating adherence to the penicillin regimen. Subsequent doses were delivered and monitored in a remote setting by nurses. After 18 months, the boy no longer required clonidine due to his increased coping capacity. A second child was recognised with similar trauma and has been taking clonidine for pre-procedural sedation for 6 months with good effect and no adverse effects. An additional child was similarly prescribed clonidine without success. Failure in that instance was attributed to lack of procedural coaching and receiving the initial dose of clonidine in an emergency department in hurried circumstances. Individualised child-focused and culturally appropriate care in remote settings is feasible: in this instance team planning for use of clonidine and procedural coaching when other measures have failed. However, for children with RHD, or other comorbidities, advice from the child's treating cardiologist is required prior to prescribing clonidine due to possible adverse consequences. These include hypotension and atrioventricular block, which could lead to haemodynamic compromise in the setting of moderate to severe RHD.

Comparison of the hydrogen powered homogeneous charge compression ignition mode with multiple injection schedules and the dual fuel mode using a twin-cylinder engine

The present work discusses the influence of injection schedules in hydrogen diesel homogeneous charge compression ignition (HDHCCI) mode, the experiments were carried out in three distinct diesel injection schedules like single pulse, double pulse and multi-pulse at low load operation. The maximum reachable hydrogen energy shares (HES) are 27.46%, 26.97% and 39.96% for a single pulse, double pulse and multi-pulse respectively. For almost all HES levels, the single pulse and double pulse HDHCCI mode provided ultra-low NO emission when compared with hydrogen diesel dual fuel (HDDF) mode. The multi-pulse injection increased the brake thermal efficiency (BTE) compared with single pulse and double pulse injection, since the timing of injection pulse 3 (IP3) in multi-pulse significantly altered the combustion characteristics of HDHCCI mode. Locating the IP3 in the window of 30–40 °BTDC (before cool flame) enhanced the BTE and reduced the brake specific energy consumption (BSEC) of the engine.

Impact of Late Dosing on Testosterone Suppression with 2 Different Leuprolide Acetate Formulations: In Situ Gel and Microsphere. An Analysis of United States Clinical Data.

Nonadherence to dosing schedules for androgen deprivation therapy increases the risk of testosterone escape for patients with prostate cancer. Two approved formulations of leuprolide acetate, the most commonly prescribed androgen deprivation therapy in the United States, use different extended release delivery technologies: an in situ gel and microspheres. We evaluated the prevalence and impact of late dosing on testosterone suppression for gel and microsphere formulations of leuprolide acetate. We retrospectively analyzed records of patients with prostate cancer treated with gel or microsphere delivery of leuprolide acetate. Analyses used 2 definitions of "month," "28-day" (late dosing after day 28, 84, 112 or 168) and "extended" (late dosing after day 32, 97, 128 and 194). Frequencies of late dosing and associated testosterone values were calculated. A total of 2,038 patients received gel and 8,360 received microsphere formulations of leuprolide acetate. More than 80% and 27% of injections were late for 28-day and extended month, respectively. For 28-day month late injections 10% (gel delivery) and 14% (microsphere delivery) of testosterone values were above 50 ng/dl, and 25% (gel) vs 33% (microsphere) were above 20 ng/dl. For extended month 18% (gel) vs 25% (microsphere) were above 50 ng/dl, and 34% (gel) vs 44% (microsphere) were above 20 ng/dl. Microsphere leuprolide acetate was 1.5 times more likely to have testosterone above 50/20 ng/dl vs gel. Least square mean testosterone was 34 ng/dl (gel) vs 46 ng/dl (microsphere) for 28-day month, and 48 ng/dl (gel) vs 76 ng/dl (microsphere) for extended month. Leuprolide acetate therapies were frequently administered late. Gel formulation demonstrated higher rates of testosterone 50 ng/dl or less and 20 ng/dl or less than microsphere formulation. Optimal testosterone suppression can impact prostate cancer progression and patient survival, and differences in extended release technology for androgen deprivation therapy appear relevant.

Aflibercept for Radiation Maculopathy (ARM Study): Year-2 Extension of a Prospective Clinical Study.

This work describes the 2-year results of the Aflibercept for Radiation Maculopathy (ARM) randomized clinical study that evaluated intravitreal vascular endothelial growth factor antagonist therapy in radiation maculopathy delivering aflibercept using a second-year collapsed, every-6-weeks, treat-and-adjust interval. Forty patients were enrolled in an institutional review board-approved clinical trial and randomly assigned to aflibercept treatment via 1 of 2 regimens: fixed, every-6-week treatment or variable, treat-and-adjust therapy centered around 6 weeks. All patients had a diagnosis of treated uveal melanoma with documented tumor control, and they had visually compromising radiation maculopathy. At conclusion of year 1, the first 30 patients were offered a collapsed single-arm variable of an every-6-weeks treat-and-adjust aflibercept injection schedule for an additional treatment year. Baseline best-corrected visual acuity (BCVA) was 20/63 at ARM study entry 20/62 at the institution of the year-2 extension. At ARM study entry baseline, spectral domain-optical coherence tomography mean central retinal thickness was 432 µm and was 294 µm at the same institution. At the 2-year study's conclusion, 76.7% (23 of 30) of eyes were better than 20/50, and only 6.7% (2 of 30) ended with a BCVA below 20/200. Final mean BCVA was 20/62 and final mean spectral domain-optical coherence tomography central retinal thickness was 286 µm, but as in year 1, this reduction in number of injections was not statistically significant. Aflibercept is effective in treating radiation maculopathy with maintained visual acuity at 2 years but continues to require an ongoing treatment approach to stabilize radiation maculopathy.

Numerical simulation and evaluation of the fracturing and tight gas production with a new dimensionless fracture conductivity (FCD) model

Hydraulic fracturing is an essential technology for the development of unconventional resources such as tight gas. The evaluation of the fracture performance and productivity is important for the design of fracturing operations. However, the traditional dimensionless fracture conductivity is too simple to be applied in real fracturing operations. In this work, we proposed a new model of dimensionless fracture conductivity (FCD), which considers the irregular fracture geometry, proppant position and concentration. It was based on the numerical study of the multistage hydraulic fracturing and production in a tight gas horizontal well of the North German Basin. A self-developed full 3D hydraulic fracturing model, FLAC3Dplus, was combined with a sensitive/reliability analysis and robust design optimization tool optiSLang and reservoir simulator TMVOCMP to achieve an automatic history matching as well as simulation of the gas production. With this tool chain, the four fracturing stages were history matched. The simulation results show that all four fractures have different geometry and proppant distribution, which is mainly due to different stress states and injection schedule. The position and concentration of the proppant play important roles for the later production, which is not considered in the traditional dimensionless fracture conductivity FCD. In comparison, the newly proposed formulation of FCD could predict the productivity more accurately and is better for the posttreatment evaluation.

Patient experience of anti-vegf intravitreal injection

Intravitreal anti-vascular epithelial growth factor (anti-VEGF) injections have revolutionised the treatment of macular diseases, but can be stressful for the patient. We surveyed 904 patients receiving injections at 5 centres in France regarding their feelings toward anti-VEGF injections. The mean age was 77.4 years, and the injections were performed mostly for age related macular degeneration (72%). Half of the patients had previously received>10 injections, 35.6% had received 3-10 injections, and 14.2% had received<3 injections. The mean (SD) stress score was 4.2 [on a scale from 1-10 (0=least stressful, 10=extremely stressful)]. Most patients (70%) reported low to moderate stress (score ≤5). The number of previous injections did not influence stress scores. Paradoxically, 61.2% of patients reported finding injections to be less stressful over time. Most patients found injections to be less traumatic than expected (64%) or just as they had anticipated (25%). Most patients (88%) were not bothered by the presence of other patients in the waiting room. Most patients (78.8%) preferred to be injected quickly before they had time to feel stressed about the procedure. Injections were generally well accepted; most patients would prefer to maintain their current schedule of injections and their current vision (55.7%), or would be willing to have more frequent injections for better vision (39.5%). Our results suggest that stress appears to be more related to the patient's psychological make-up than to the treatment experience or the number of injections received.

Investigating Possible Etiologies of Post-Exposure Prophylaxis Failure and Deaths From Rabies Infection: Case Reports

Rabies virus, as a neurotropic agent, is transmitted to humans usually after animal biting. Rabies is endemic in most Middle Eastern countries. Pre-exposure Prophylaxis (PrEP) program is recommended for high-risk populations in endemic areas. The present study reported 7 deaths from rabies infection despite human Post-Exposure Prophylaxis (PEP) and the evolution of their possible etiologies from 2014 to 2018 in Iran. In this study, 29 rabid human deaths were evaluated despite PEP in 2014-2018. Seven people deceased despite receiving PEP. The most damaged organs were hands and face (71.43%). Injecting anti-Rabies Immunoglobulin (RIG) around the wound, improper cleansing, and delayed PEP were the main causes of PEP failure. In addition, immunodeficiency in a patient was another cause of failure. Our obtained data suggested that immediate precise measures after exposure based on the World Health Organization (WHO) recommendation, maintaining the temperature integrity (cold chain) of vaccines, and RIGs during transportation, and performing detailed injection schedule could prevent PEP failure in most cases. Furthermore, society’s awareness plays a key role in controlling the disease, especially in endemic areas.

Optimization of diesel fuel injection strategies through applications of cooperative particle swarm optimization and artificial bee colony algorithms

New engine hardware and injection strategies allow modern engines to meet stringent emissions regulations but can require extensive engine testing to identify optimum operating points. Swarm intelligence algorithms, which do not require knowledge of the search space gradient, can provide a short cut in finding optimum operating parameters in reduced experimental time than a traditional design of experiments study. In this paper, a modified artificial bee colony (ABC) algorithm and a cooperative particle swarm optimization (CPSO) algorithm are applied to triple and quadruple injection routines. The optimization was applied directly to the operation of a four-cylinder turbocharged production diesel engine operating at a high exhaust gas recirculation rate and medium load. Six and eight variable optimizations were carried out for triple and quadruple injection schedules, respectively. In experimental testing, the cooperative particle swarm optimizer significantly reduced soot and carbon monoxide emissions in only 84 engine tests when using a pilot-pilot-main-post schedule. The modified artificial bee colony algorithm took 176 engine tests to optimize a pilot-main-post triple-injection schedule and was not applied to the four-injection routine.

Coupled Thermo–Hydro–Mechanical Modeling of Hydro-Shearing Stimulation in an Enhanced Geothermal System in the Raft River Geothermal Field, USA

The Raft River Enhanced Geothermal System (EGS) demonstration project aims to improve the geothermal production by enhancing the reservoir permeability via shear stimulation in well RRG-9. In this paper, we performed a series of 3D thermo–hydro–mechanical (THM) simulations to investigate the influence of hydraulic and thermal effects on the development of this EGS. The model includes synthetic fracture populations based on borehole televiewer images and in-situ stress measurements from well RRG-9. Fracture permeability evolution is determined using an empirical permeability law developed from laboratory experiments. The model was calibrated by comparing the hydraulic response to field observations, including wellhead pressure, injection rate, and well injectivity. Particularly, we analyzed the enhancement of reservoir permeability and the spatial extent of the stimulation zone for the given injection schedule. Our results indicate that the permeability enhancement of fractured geothermal reservoir is caused by the combined effects of injection-induced cooling and fluid pressure increase. The decrease of temperature plays a dominant role in reactivation of natural fractures under the hydro-shearing mechanism, while the higher injection pressure promotes shear failure and enlarges the stimulation zone. For the specified extensional stress state, the model favors greatest permeability enhancement along the maximum horizontal principal stress, a moderate vertical enhancement, and a smaller gain along the minimum horizontal principal stress.

Botulinum Toxin for Chronic Lateral Epicondylitis (LE).

Lateral epicondylitis is a common disease in orthopaedic practice. Although the majority of cases do not become chronic, patients who do not respond to the initial treatment may suffer from pain in the long term and effective treatment is challenging. The off-label use of botulinum toxin is one of the common potential indications for the substance in orthopaedics and traumatology. In a literature review of 2000 - 2019, eight EBM ≥ level 3 studies evaluating the use of botulinum toxin in lateral epicondylitis were found. Five of these studies evaluated botulinum toxin versus placebo in chronic cases; two other studies compared botulinum toxin with corticosteroids in acute cases and classic Hohmann surgery in chronic cases; the eighth study compared botulinum toxin in two different injection sites and corticosteroids by classic injection. Our findings suggest that the use of this substance may be a treatment option in refractory chronic cases before surgery is indicated. The working group on botulinum toxin in O & T of the International Musculoskeletal Pain Society (IMPS/IGOST) introduced an alternative injection schedule, which combines findings from the recent clinical literature with practical experience in order to reduce the risk of side effects while ensuring treatment effectiveness. Using 2 simple tests of function and, if necessary, sonographic verification, 2 separate injection sites in the extensor carpi radialis or the extensor digitorum can be identified by palpation. The tendon level on the lateral epicondyle acts as the third injection site. With optimal use of the ampoule content, the 3 injection sites can be infiltrated individually, depending on the muscle status. On the one hand, this enables treatment to take place after a dual therapy approach and, on the other hand, the risk of overdose in a muscle with subsequent unnecessary muscle weakening can be reduced.

Analysis of Clinical Characteristics and Prognostic Risk Factors of HLH Children with Central Nervous System Involvement

To investigate the clinical characteristics and prognostic risk factors of HLH children with central nervous system (CNS) involvement so as to provide more reference for further improving the prognosis of HLH children. The clinical data of 45 HLH children with CNS involvement treated in our hospital from January 2006 to October 2016 were collected and analyzed retrospectively. The clinical characteristics of HLH children with CNS involvement were recorded, moreover the possible factors influencing the prognosis of HLH children with CNS involvement were analyzed using univariate and multivariate analysis through the establishment of Cox risk ratio model. Among 45 HLH children with CNS involvement, male was 19 cases and female was 26 cases. The median age of 4.0 years old (1.0-15.1). The detection showed that EBV found in 38 cases (84.44%), CMV infection in 1 case (2.22%), bacterial infection in 3 cases (6.67%), connection tissue disease in 1 case (2.22%) and indefinite etiology infection in 2 cases (4.44%). After lumbar puncture of 27 HLH children with CNS involvement, 10 cases (37.04%) showed cerebrospinal fluid abnormality. In addition, 22 cases showed the craniography abnormality. The follow-up results showed that the OS rate of 1 year was 46.67% (21/45), the OS rate of 3 years was 44.44% (20/45); the median survival time was 5.0 months. The OS analysis indicated that 1 years OS rate of diseased children with cerebrospinal fluid abnormality was significantly lower than that of diseased children with cerebrospinal fluid normality (10/45 vs 17/45) (P＜0.05), and 1 years OS rate of diseased children who not received intrathecal injection was significantly lower that of diseased children who received intrathecal (10/45 vs 17/45) (P＜0.05). The univariate analysis showed that the symptoms of nervous system, abnormal cerebrospinal fluid, absence of intrathecal injection and treatment schedule all were the risk factors affecting the prognosis of HLH children with CNS involvement (P＜0.05). The multivariate analysis by Cox risk model showed that abnormal cerebrospinal fluid and absence of intrathecal injection were independent risk factors for of HLH children with CNS involvement (P＜0.05). The clinical prognosis of HLH children with CNS involvement is relatively poor, moreover some of HLH children with CNS involvement have neural sequelae. The cerebrospinal fluid abnormality and absence of intrathecal injection are independent risk factors leading to poor prognosis for HLH clildren with CNS involvement.

An optimized model of calculating optimal packing ratio for graded proppant placement with consideration of proppant embedment and deformation

The method of micro-sized Graded Proppant Placement (GPP) has been proposed in the industry to increase the size of the stimulated zone in naturally fractured reservoirs. The models of determining the Optimal Proppant Packing Ratio (OPPR) and the optimal injection schedule have also been established. However, all the previous studies neglected the impact of Proppant Embedment into fracture wall and Proppant Deformation (PEPD), and therefore significant discrepancies between modeling results and experimental results have been observed. In this study, models of calculating PEPD are established and incorporated into the GPP model, and the influences of proppant embedment and deformation on OPPR, optimal injection schedule and predicted post-stimulation productivity increase are investigated. Conductivity Correction Factor (CCF) is introduced to find the OPPR and the results are compared with the results obtained from previous models which are based on Permeability Correction Factor (PCF).The results show that smaller proppant Elastic Modulus or smaller rock Elastic Modulus leads to bigger OPPR and lower PCF. The CCF -based OPPR matches better with previous experimental results than the PCF -based value. The study also shows that with consideration of PEPD, OPPR is significantly larger; the optimal proppant concentrations at different stages of graded proppant injection are accordingly larger, and the predicted folds of productivity increase after stimulation is much lower.The results from this study can be used to optimize the planning of GPP. For the stimulations of soft formations like CBM, shale etc. or the stimulations where less-rigid proppants like silica sand or walnut shell are used, the findings of this study are even more important. If the proppants and the formation rock are assumed to be rigid bodies and PEPD are neglected in such situations, 32.5% lower of proppant concentration will be caused, which will consequently lead to under-propping of the fracture and the productivity will not be maximized supposedly. Meanwhile, the predicted folds of productivity increase will be overestimated by 27.5% maximally. The larger the stimulation zone, the stronger the influence of PEPD. PEPD must be considered when planning a large-scale GPP in soft formations.This study is a continuation of the studies conducted by the authors earlier. The major novel elements are that PEPD are considered, the influences of PEPD are investigated, and fracture conductivity is used instead of permeability to find the optimal proppant packing ratio.

Effect of pilot and post fueling on the combustion and emission characteristics of a light-duty diesel engine powered with diesel and waste cooking biodiesel blend

ABSTRACT Biodiesel produced from waste resources provides both environmental and economic benefits. The use of biodiesel blends in tandem with advanced fuel injection strategies enables effective control over engine-out emissions. The current study investigates the effect of the pilot and post fuel injection on combustion and emission characteristics of a light-duty diesel engine fueled with standard diesel and waste cooking biodiesel blend. The engine adopted for this study is an automotive common rail direct injection (CRDI) diesel engine, wherein the electronically controlled fuel injection system provides flexibility to control single and multiple injection schedules along with the provision for change in fuel injection pressure. A blend of 80% diesel and 20% waste cooking biodiesel (B20) was tested at four-part loads and three fuel injection pressures. The test results indicated a considerable reduction in smoke (84.4%), hydrocarbon (71.8%), and carbon monoxide (46.8%), compared to the base diesel (D100) operating at a single injection and lower fuel injection pressure. Also, Brake thermal efficiency was improved by 4.46%. However, nitric oxide emission was found to be 15% higher due to the higher fuel injection pressure. The experimental results affirm that the usage of pilot and post-injection along with higher fuel injection pressure for waste cooking biodiesel blend yielded a significant reduction in emissions at part-load condition.

Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippocampal Senescence.

Markers of brain aging and cognitive decline are thought to be influenced by peripheral inflammation. This study compared the effects of repeated lipopolysaccharide (LPS) treatment in young rats to age-related changes in hippocampal-dependent cognition and transcription. Young Fischer 344 X Brown Norway hybrid rats were given intraperitoneal injections once a week for 7weeks with either LPS or vehicle. Older rats received a similar injection schedule of vehicle. Old vehicle and young LPS rats exhibited a delay-dependent impairment in spatial memory. Further, LPS treatment reduced the hippocampal CA3-CA1 synaptic response. RNA sequencing, performed on CA1, indicated an increase in genes linked to neuroinflammation in old vehicle and young LPS animals. In contrast to an age-related decrease in transcription of synaptic genes, young LPS animals exhibited increased expression of genes that support the growth and maintenance of synapses. We suggest that the increased expression of genes for growth and maintenance of synapses in young animals represents neuronal resilience/recovery in response to acute systemic inflammation. Thus, the results indicate that repeated LPS treatment does not completely recapitulate the aging phenotype for synaptic function, possibly due to the chronic nature of systemic inflammation in aging and resilience of young animals to acute treatments.

Oncolytic virus therapy benefits from control theory.

Oncolytic virus therapy aims to eradicate tumours using viruses which only infect and destroy targeted tumour cells. It is urgent to improve understanding and outcomes of this promising cancer treatment because oncolytic virus therapy could provide sensible solutions for many patients with cancer. Recently, mathematical modelling of oncolytic virus therapy was used to study different treatment protocols for treating breast cancer cells with genetically engineered adenoviruses. Indeed, it is currently challenging to elucidate the number, the schedule, and the dosage of viral injections to achieve tumour regression at a desired level and within a desired time frame. Here, we apply control theory to this model to advance the analysis of oncolytic virus therapy. The control analysis of the model suggests that at least three viral injections are required to control and reduce the tumour from any initial size to a therapeutic target. In addition, we present an impulsive control strategy with an integral action and a state feedback control which achieves tumour regression for different schedule of injections. When oncolytic virus therapy is evaluated in silico using this feedback control of the tumour, the controller automatically tunes the dose of viral injections to improve tumour regression and to provide some robustness to uncertainty in biological rates. Feedback control shows the potential to deliver efficient and personalized dose of viral injections to achieve tumour regression better than the ones obtained by former protocols. The control strategy has been evaluated in silico with parameters that represent five nude mice from a previous experimental work. Together, our findings suggest theoretical and practical benefits by applying control theory to oncolytic virus therapy.

Computational optimization of reactivity controlled compression ignition combustion to achieve high efficiency and clean combustion

One of the major limitations of reactivity controlled compression ignition is higher unburned hydrocarbon and carbon monoxide emissions and lower thermal efficiency at part load operating conditions. In the present study, a combined numerical approach using a commercial three-dimensional computational fluid dynamics code CONVERGE along with artificial neural network and genetic algorithm is presented to address the above limitation. A production light-duty diesel engine is modified to run in reactivity controlled compression ignition by replacing an existing mechanical fuel injection system with a flexible electronic port fuel injection and common rail direct injection systems. The injection schedules of port fuel injection and direct injection injectors are controlled using National Instruments port and direct injection driver modules. Upon validation of combustion and emission parameters, parametric investigations are carried out to establish the effects of direct-injected diesel fuel timing start of injection (SOI), premixed fuel ratio and intake charge temperature on the engine performance and emissions in reactivity controlled compression ignition. The results obtained show that the start of injection timing and intake charge temperature significantly influence combustion phasing, while the premixed fuel ratio controls mixture reactivity and combustion quality. By utilizing the data generated with the validated computational fluid dynamics models, the artificial neural network models are trained to predict the engine exhaust emissions and efficiency. The artificial neural network models for gross indicated efficiency and oxides of nitrogen (NOx) are then coupled with genetic algorithm to maximize gross indicated efficiency while keeping the NOx and soot emissions within Euro VI emission limits. By optimizing the start of injection timing, premixed fuel ratio and intake charge temperature simultaneously using the artificial neural network models coupled with genetic algorithm, 19% improvement in gross indicated efficiency, 60% and 64% reduction in hydrocarbon and carbon monoxide emissions, respectively, are obtained in reactivity controlled compression ignition compared to the baseline case.

Using saline or brackish aquifers as reservoirs for thermal energy storage, with example calculations for direct-use heating in the Portland Basin, Oregon, USA

Tools to evaluate reservoir thermal energy storage (RTES; heat storage in slow-moving or stagnant geochemically evolved permeable zones in strata that underlie well-connected regional aquifers) are developed and applied to the Columbia River Basalt Group (CRBG) beneath the Portland Basin, Oregon, USA. The performance of RTES for heat storage and recovery in the Portland Basin is strongly dependent on the operational schedule of heat injection and extraction. We examined the effects of the operational schedule, based on an annual solar hot water supply pattern and a building heating demand model, using heat and fluid flow simulations with SUTRA. We show RTES to be feasible for supply of heating energy for a large combined research/teaching building on the Oregon Health and Science University South Waterfront expansion, an area of planned future development. Initially, heat is consumed to increase the reservoir temperature, and conductive heat loss is high due to high temperature gradients between the reservoir and surrounding rock. Conductive heat loss continues into the future, but the rate of heat loss decreases, and heat recovery efficiency of the RTES system increases over time. Simulations demonstrate the effects of varying heat-delivery rate and temperature on the heat production history of the reservoir. If 100% of building heating needs are to be supplied by combined solar/RTES, then the solar system must be sized to meet building needs plus long-term thermal losses (i.e., conductive losses once the system is heated to pseudo-steady state) from the RTES system. If the solar heating system barely meets these criteria, then during early years, less than 100% of the building demand will be supplied until the reservoir is fully-heated. The duration of supplying less than 100% of building demand can be greatly shortened by pre-heating the reservoir before building heating operations or by adding extra heat from external sources during early years. Analytic solutions are developed to evaluate efficacy and to help design RTES systems (e.g., well-spacing, thermal source sizing, etc.). A map of thermal energy storage capacity is produced for the CRBG beneath the Portland Basin. The simulated building has an annual heat load of ∼1.9 GWh, and the total annual storage capacity of the Portland Basin is estimated to be 43,400 GWh assuming seasonal storage of heat yields water from which 10 °C can be extracted via heat exchange, indicating a tremendous heating capacity of the CRBG.

Investigation on the effect of injection schedule and EGR in hydrogen energy share using common rail direct injection dual fuel engine

In this research work, four different diesel injection schedules have been experimented at a BMEP of 2 bar (Low load) in hydrogen diesel dual fuel (HDDF) mode, which are namely single pulse, double pulse phase-1, double pulse phase-2 and multi-pulse. The maximum possible hydrogen energy shares (HES) for single pulse, double pulse phase-1, double pulse phase-2 and multi-pulse injection schedules were 73.99%, 48.98%, 34.46% and 24.39% respectively. Over the injection schedules, double pulse phase-2 improved the brake thermal efficiency (BTE) from 19.50% (single pulse) to 21.61% with a penalty in NO emission. On the other hand, multi-pulse moderately increased the BTE with significant reduction in NO beside rise in smoke emission. At a BMEP of 5 bar (Medium load) operation, there was a considerable reduction in NO emission at maximum range of HES level with 18.21% of EGR, moreover the engine stability was improved with minor increase in smoke emission.

GABAA Receptor Subtypes and the Reinforcing Effects of Benzodiazepines in Remifentanil-Experienced Rhesus Monkeys

BackgroundOpioid-use disorder is associated with a high degree of co-abuse with benzodiazepines. While the mechanisms underlying the co-abuse of opioids and benzodiazepines remain unknown, α1 subunit-containing GABAA receptors may play a critical role in the reinforcing effects of benzodiazepine-type compounds, depending on whether the monkeys have a history of benzodiazepine or stimulant self-administration. The present study extended our prior research by comparing the reinforcing effects of a compound lacking activity at α1 subunit-containing GABAA receptors with the reinforcing effects of non-selective GABAA receptor positive allosteric modulators in monkeys with a history of opioid self-administration. MethodsThe reinforcing effects of L-838,417 (partial intrinsic efficacy at α2, α3, and α5 subunit-containing GABAA receptors, but no efficacy at α1 subunit-containing GABAA receptors, i.e., “α1-sparing compound”) were compared with those of the non-selective GABAA receptor partial modulator MRK-696, and non-selective GABAA receptor full modulators, triazolam and lorazepam, in rhesus monkeys (n = 3) experienced in remifentanil self-administration under a progressive-ratio schedule of intravenous drug injection. ResultsNeither the partial modulator nor the α1-sparing compound were self-administered above vehicle levels. The full modulators triazolam and lorazepam were self-administered significantly above vehicle levels, albeit at lower levels than remifentanil. ConclusionsOur findings suggest that relatively high efficacy at one or more GABAA receptor subtypes is required for a compound to have reinforcing effects in monkeys with a history of remifentanil self-administration, in contrast to monkeys with benzodiazepine or stimulant self-administration histories.

A real-world single-center retrospective study on efficacy and safety of pegylated interferon alpha-2a in patients with myeloproliferative neoplasm.

e19536 Background: Pegylated forms of interferon (PEG-IFN) have a better pharmacologic profile than short-acting interferons, resulting in a more convenient less-frequent schedule of injections, less immunogenicity and possibly less toxicity. Several clinical studies of PEG-IFN-α-2a have reported promising results in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Herein, we present the outcomes of MPN patients treated with PEG-IFN-α-2a seen outside of a clinical trial setting at a single center. Methods: Thirty-five MPN Patients treated with PEG-IFN-α-2a between January 2014 and October 2019 were included this retrospective analyses. Therapeutic responses for ET and PV were calculated by the revised ELN/IWG-MRT criteria. Responses in myelofibrosis (MF) were calculated by both EUMNET and ELN/IWG-MRT criteria. Best responses over all cycles of treatment were assessed. Molecular data was limited to JAK V617F. Results: Twenty patients with ET, 13 with PV and two with MF were enrolled in this study. The median age at diagnosis was 47 years (range; 21-83 years). JAK2 V617F mutation was detected in 16 patients (45.7%). Overall, the majority of patients (62.9%) had received at least one prior cytoreductive therapy for underlying disease. Median starting dose of PEG-IFN-α-2a was 90 mcg/week via self injection (range: 45-135 mcg/w). Treatment duration was pursued for a median duration of 21.4 months (range: 1.2-109.8). In the PV/ET group 33 patients were evaluated and overall best response rate was 87.8% (CR in 15 pts and PR in 14 pts). In the MF group (n = 2); a PR was seen in one patient and CR in one patient. No vascular events occurred within the cohort while on therapy. Of the eight patients receiving at least phelebotomy per month, all patients became phelobotomy independent with therapy. Of the 20 ET patients, 12 patients (60%) had platelet normalization (&lt; 450 x 109/L). Among all patients, fatigue (31.4%), muscle pain (20%) and depression (8.6%) were the most common adverse events (AEs). Any grade of hematological AEs was not seen with PEG-IFN-α-2a. Eleven patients discontinued therapy secondary to: treatment associated severe AEs in 8 patients, lack of response in two patients and pregnancy in one patient. No death was reported during the analyses period. Conclusions: Our results suggest that PEG-IFN-α-2a remains a viable treatment option especially for younger patients who want to avoid prolonged cytotoxic therapy.