Optimal control study to enhance oil production in labscale Vapex by varying solvent injection pressure with time

In this study, we determine and validate optimal policies of solvent injection pressure versus time to enhance oil production in labscale Vapex or vapor extraction of heavy oil. The study utilizes propane as solvent for a heavy oil of viscosity 14 500 mPa s. The necessary conditions for maximum oil production are derived using a detailed mass transfer model with interfacial solvent concentration versus time as a control function. Based on these conditions, a computational algorithm is developed and implemented to determine the optimal control, which is then converted into the optimal policy of solvent injection pressure versus time using experimental data. The experiments demonstrate that the optimal policy enhances oil production by 20–37% compared with that using constant solvent injection pressure. Moreover, the average deviation of the optimally calculated oil production from its experimental counterpart, both obtained using the same optimal solvent injection policy, is found to be a low value of 4.8%. Copyright © 2015 John Wiley & Sons, Ltd.     

The modulation of spinal growth with nitinol intervertebral stapling in an established swine model

Purpose

Anterior spinal stapling for the treatment of adolescent idiopathic scoliosis has been shown to slow progression in small curves; however, its role in larger curves remains unclear. The purpose of this study was to evaluate the effectiveness of nitinol staples to modulate spinal growth by evaluating the two-dimensional and three-dimensional morphological and histological effects of this method in a well-established porcine model.

Methods

Three immature Yucatan miniature pigs underwent intervertebral stapling. Two staples spanned each of three consecutive mid-thoracic discs and epiphyses. Monthly radiographs were obtained. Computed tomography (CT) was conducted at harvest after 6 months of growth. Measurements of wedging and height for each disc and vertebral body were conducted. Micro CT was used to compare physeal closure between stapled and non-stapled levels. Histology of the growth plate also compared the hypertrophic zone thickness for control and stapled vertebrae.

Results

After 6 months of stapled growth, the average coronal Cobb angle of the stapled segments increased by 7.7 ± 2.0° and kyphosis increased by 3.3 ± 0.6° compared to preoperative curves. Increased vertebral wedging and decreased disc height (p < 0.001) were noted in stapled regions. Overall, 26 ± 23 % of each growth plate was closed in the stapled segments, with 6 ± 8 % closure in the unstapled levels. No difference was observed regarding the hypertrophic zone height when comparing instrumented to uninstrumented levels, nor was a difference recognized when comparing right versus left regions within stapled levels alone.

Conclusions

Six months of nitinol intervertebral stapling created a mild coronal and sagittal deformity associated with reduced vertebral and disc height, and increased coronal vertebral and sagittal disc wedging.     

ACEA-1328, a NMDA receptor/glycine site antagonist, acutely potentiates antinociception and chronically attenuates tolerance induced by morphine.

The effect of ACEA-1328, a competitive and systemically bioavailable NMDA receptor/glycine site antagonist, was studied on morphine-induced antinociception and tolerance in CD-1 mice using the tail flick test. To study the effect of acute administration of ACEA-1328 on morphine-induced antinociception, mice were injected with either ACEA-1328 (1, 5, and 10 mg kg(-1)) or Bis-Tris (0.2 m) immediately followed by an injection of morphine and tested for antinociception 30 min later. ACEA-1328 significantly increased the antinociceptive potency of morphine. To study the effect of chronic administration of ACEA-1328 on morphine-induced antinociception and tolerance, mice were treated, either once per day for 9 days or twice daily for 4 days, with ACEA-1328 or with the vehicle. Mice were then, within 1 min, injected daily with either morphine or saline. On the day of the test, mice were injected with only morphine and tested for antinociception 30 min later. In comparison to the acute effect of ACEA-1328, chronic treatment with the NMDA receptor/glycine site antagonist did not affect the antinociceptive potency of morphine. Chronic treatment with morphine, by both methods, produced a significant degree of tolerance. Concurrent administration of ACEA-1328 with the opioid analgesic completely blocked morphine tolerance. Our results demonstrate that acute, but not chronic, treatment with ACEA-1328 increased the antinociceptive potency of morphine. Furthermore, co-administration of the NMDA receptor antagonist with morphine abolished the development of tolerance. Overall, the data support a growing body of evidence showing that activation of the NMDA receptor plays a functional role in opioid-induced antinociception and tolerance.     

Improved time to progression for transarterial chemoembolization compared with transarterial embolization for patients with unresectable hepatocellular carcinoma

BackgroundEmbolizing branches of the hepatic artery lengthens survival for patients with unresectable hepatocellular carcinoma (HCC), but the benefit of combining chemotherapy with the embolizing particles remains controversial.MethodsA retrospective review was undertaken of sequential patients with advanced HCC undergoing embolization in the past 10 years at 2 neighboring institutions and with 2 years of follow-up data. TACE was generally performed with doxorubicin plus mitomycin C. Results: One hundred twenty-four patients were included; 77 received TACE and 47 received TAE. On multivariable analysis stratified by institution, type of embolization and CLIP score significantly predicted PFS and time to progression (TTP), whereas CLIP score and AFP independently predicted overall survival (OS). TACE significantly prolonged PFS and TTP (P = .0004 and P = .001, respectively), but not OS (P = .83).ConclusionsThe addition of chemotherapy to TAE prolongs PFS and TTP. Future efforts should focus on adjunctive therapies after the embolization to increase survival.     

The vascular niche: home for normal and malignant hematopoietic stem cells

Hematopoietic stem cells (HSCs) are uniquely capable of self-renewal and provision of all of the mature elements of the blood and immune system throughout the lifetime of an individual. HSC self-renewal is regulated by both intrinsic mechanisms and extrinsic signals mediated via specialized microenvironments or 'niches' wherein HSCs reside. HSCs have been shown to reside in close association with bone marrow (BM) osteoblasts in the endosteal niche and also in proximity to BM sinusoidal vessels. An unresolved question surrounds whether the endosteal and vascular niches provide synchronous or redundant regulation of HSC fate or whether these niches provide wholly unique regulatory functions. Furthermore, while some aspects of the mechanisms through which osteoblasts regulate HSC fate have been defined, the mechanisms through which the vascular niche regulates HSC fate remain obscure. Here, we summarize the anatomic and functional basis supporting the concept of an HSC vascular niche as well as the precise function of endothelial cells, perivascular cells and stromal cells within the niche in regulating HSC fate. Lastly, we will highlight the role of the vascular niche in regulating leukemic stem cell fate in vivo.     

The accuracy and precision of Kilovoltage Intrafraction Monitoring (KIM) six degree-of-freedom prostate motion measurements during patient treatments

Background and purpose

To perform a quantitative analysis of the accuracy and precision of Kilovoltage Intrafraction Monitoring (KIM) six degree-of-freedom (6DoF) prostate motion measurements during treatments.

Effects of acid-reducing agents on the pharmacokinetics of lopinavir/ritonavir and ritonavir-boosted atazanavir

A total of 71 HIV-negative healthy adults were randomized to 1 of 6 regimens to receive lopinavir/ritonavir tablets 400/100 mg twice daily (bid) or 800/200 mg once daily (qd) or atazanavir 300 mg + ritonavir 100 mg qd from study days 1 to 15 with a moderate-fat meal. One hour before breakfast, either omeprazole 40 mg qd was administered on study days 11 through 15, or a single dose of ranitidine 150 mg was administered on study day 11. Lopinavir, atazanavir, and ritonavir pharmacokinetics were determined on study days 10, 11, and 15 and compared using point estimates and 90% confidence intervals (CIs). The point estimates for lopinavir Cmax and AUCtau were in the range of 0.92 to 1.08, with 90% CI contained within the range of 0.80 to 1.25 after coadministration of omeprazole or ranitidine. The point estimates for atazanavir Cmax and AUCtau were decreased by 48% to 62% with the upper bound of the 90% CI 相似文献   

Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations

BACKGROUND AND PURPOSE

Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS.

EXPERIMENTAL APPROACH

The effects of 8 weeks of treatment with either vitamin D₂ at 25 000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV_BS) and aortic valve : outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function.

KEY RESULTS

Treatment with ramipril significantly reduced AV_BS and improved aortic valve : outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment.

CONCLUSIONS AND IMPLICATIONS

Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor.     

Development and implementation of a cross-border HIV prevention intervention for injection drug users in Ning Ming County (Guangxi Province), China and Lang Son Province, Vietnam

This paper describes the background and early implementation of a peer-based HIV prevention intervention involving social marketing of sterile needles and syringes for injection drug users (IDUs) in a border region of northern Vietnam and southern China. Peer educators collect and safely dispose of used needles and syringes and provide IDUs with a choice of new needles/syringes or vouchers redeemable in pharmacies and clinics for new needles/syringes. The project arose from a pattern of changing drug use and increasing HIV infection in the region but its development took 4 years and faced many challenges. Implementation of the intervention posed a new set of challenges for the participating health departments, police, peer educators, pharmacists, injection drug users, and the communities at large. Early implementation of the project has revealed successful multi-sectoral collaboration, and broad acceptance by IDUs of pharmacy vouchers and distribution of new needles/syringes. However, IDUs’ persistent fear of the police, particularly in Vietnam, has required reliance on separate collection by peer educators of used needles/syringes and distribution of pharmacy vouchers and new needles. In China, new needles/syringes and vouchers are largely being provided through exchange. Understanding the development and implementation challenges and the strategies that were successful in overcoming them (including the importance of being flexible and adaptable to contextual factors) may be useful to those interested in launching similar, much-needed interventions in other parts of the world.     

Inhibiting proliferation of gefitinib-resistant, non-small cell lung cancer

Purpose

Sensitivity to a tyrosine kinase inhibitor (TKI) is correlated with the presence of somatic mutations that affect the kinase domain of epidermal growth factor receptor (EGFR). Development of resistance to TKI is a major therapeutic problem in non-small cell lung cancer (NSCLC). Aim of this study is to identify agents that can overcome TKI resistance in NSCLC.

Methods

We used a carefully selected panel of 12 NSCLC cell lines to address this clinical problem. Initially, the cell lines were treated with a variety of 10 compounds. Cellular proliferation was measured via MTT assay. We then focused on the gefitinib-resistant, EGFR mutant cell lines [H1650: exon 19 and PTEN mutations; and H1975: exons 20 (T790M) and 21 (L858R)] to identify agents that could overcome TKI resistance.

Results

Both 17-DMAG (Hsp90 inhibitor) and belinostat (histone deacetylase inhibitor, HDACi) effectively decreased the growth of almost all NSCLC lines. Also, belinostat markedly decreased the expression of EGFR and phospho-Akt in the cells. Combination of 17-DMAG and belinostat synergistically inhibited in vitro proliferation of these cells. Furthermore, both agents and their combination almost completely prevented TKI-resistant tumor formation (EGFR T790M mutation) in a xenograft model.

Conclusion

These results suggest that the combination of 17-DMAG and belinostat should be examined in a clinical trial for TKI-resistant NSCLC cell.