Notable Effectiveness Research Articles

Current Perspectives on the Impact of the National Diabetes Prevention Program: Building on Successes and Overcoming Challenges.

To address the public health and economic burden of type 2 diabetes, the Centers for Disease Control and Prevention (CDC) began dissemination of the National Diabetes Prevention Program (NDPP) in the United States in 2010. Based on the intensive lifestyle intervention from a large efficacy trial, the NDPP aims to reduce incidence through lifestyle change and weight loss. This narrative review summarizes evidence on reach, effectiveness, and sustainability of the NDPP, while highlighting opportunities to overcome challenges in these areas. Major successes include reaching hundreds of thousands of at-risk individuals across the nation, with notable effectiveness upon full participation and widespread insurance coverage. Yet, more work is needed to ensure greater public health impact, particularly among priority populations at heightened risk who also experience disparities in program outcomes. Preliminary evidence suggests a number of strategies may improve reach and effectiveness of the NDPP, often with more rigorous study needed prior to widespread uptake. Updating the NDPP to better match the current evidence-base may also be important, such as directly targeting glycemia with a patient-centered approach and promoting metformin as an adjunct or second-line treatment. Finally, revisiting pay-for-performance reimbursement models may be critical to sustainability by ensuring adequate availability of suppliers and ultimately reducing diabetes prevalence.

Abstract P3-11-06: Pre-clinical assessment of combined ABT-263/Navitoclax and ABT-414 or ABBV-321 treatment for EGFR-expressing TNBC

Abstract Despite a notable incidence of EGFR1 copy number alterations and/or enrichment of EGFR protein in a significant fraction of TNBCs, clinical application of classical EGFR-targeted therapeutics has been discouraging. Tumor specific EGFR-targeted antibodies (ABT-806) and their antibody-drug conjugates (ADC:414;321), which eliminate side effects associated with systemic anti-EGFR treatments, represent promising alternative therapeutic approaches. 414, comprised of 806 conjugated to the powerful cytotoxic MMAF, has demonstrated notable effectiveness within EGFR1-amplified/mutated tumors. However, since TNBCs are often enriched for EGFR expression in the absence of EGFR1 amplification or mutation, we explored whether neutralization of BCL-2/XL via ABT-263/Navitoclax would enhance the effectiveness of 414. Here, we evaluated 414+263 in a panel of seven EGFR-expressing patient-derived xenograft (PDX) models of TNBC. Tumor-bearing mice were randomized into one of two groups, either 414+263 or placebos. Tumor volumes were calculated via caliper-based measurements pre- and post-treatment. 14 days post-treatment, tumor growth inhibition was observed in five out of seven combination-treated tumor models; however, consistent tumor regressions were only observed in one of these models (HCI-010). Compared to the other PDX models, HCI-010 tumors were distinguished by EGFR1 low polysomy and the highest EGFR expression levels. To further explore combined treatment within HCI-010, we evaluated single-agents. To determine EGFR relevance, we also included a non-tumor targeted ADC (095-MMAF) as a single agent or in combination with 263. Tumor growth inhibition & regressions were observed in either 263 or 414+263 treated tumors. These responses were most significant under combined treatment conditions (avg. regression=40%). Tumor growth was unaffected by 414 or 095-MMAF single agents. Tumors treated with 095-MMAF+263 were comparable to single agent 263. Based upon these results, we considered an alternative EGFR-targeted ADC (321). 321, comprised of an affinity-matured version of 806 conjugated to the powerful cytotoxic PBD, exhibits enhanced EGFR affinities and has demonstrated notable effectiveness within EGFR-overexpressing tumors. To evaluate 321 combined treatment within HCI-010, tumor-bearing mice were randomized into six groups: placebos; 263; 321; 263+321; 095-PBD; 263+095-PBD. Tumor growth inhibition & tumor regressions were maintained under 263 and, unlike 414, also observed under 321 treatments. 321 resulted in dramatic tumor regressions (avg. regression=66%). Notably, 263 enhanced the effectiveness of 321 as evidenced by even more dramatic and near complete tumor regressions (avg. regression=88%). We extended these studies to include HCI-025, an additional PDX characterized by EGFR1 low polysomy and EGFR expression levels comparable to HCI-010. To evaluate 321 combined treatment within HCI-025; we performed a similar six-group study. HCI-025 tumors were also sensitive to single agent 321 (avg. regression=36%). Similar to HCI-010 and as evidenced by dramatic tumor regressions, 263 also enhanced the effectiveness of 321 within HCI-025 (avg. regression=68%). 095-PBD and 263+095-PBD also resulted in HCI-010 and HCI-025 tumor growth inhibition & regressions; however supportive of EGFR-mediated effects, 321 responses were greater than 095-PBD and 263+321 responses were greater than 263+095-PBD. These results underscore the significant potential of BCL-2/XL-inhibitors to enhance the effectiveness of cytotoxic agents delivered via ADCs. Notably, this strategy avoids the toxicities associated with systemic chemotherapy and BCL-2/XL-inhibitors. These results also highlight the translational relevance of 321+263, within the context of EGFR-expressing TNBC. Citation Format: Jason J Zoeller, Aleksandr Vagodny, Veerle W. Daniels, Krishan Taneja, Benjamin Y. Tan, Yoko S. DeRose, Maihi Fujita, Alana L. Welm, Anthony Letai, Joel D. Leverson, Vincent Blot, Roderick T. Bronson, Deborah A. Dillon, Joan S. Brugge. Pre-clinical assessment of combined ABT-263/Navitoclax and ABT-414 or ABBV-321 treatment for EGFR-expressing TNBC [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-06.

Cross term constructed Lyapunov function based two-time scale controller design and vibration suppression for a rotating hub-beam system

In this article, modeling and control of a rotating hub-beam system are studied. The system consists of a solid rotating cylinder and an attached flexible arm with a payload at the end. The rotation is supposed to be in the presence of gravity and the flexible arm is assumed to be a Euler-Bernoulli beam. To derive the equations of motion of the system, Lagrange’s method is applied. Moreover, Galerkin’s technique is employed to discretize the equations of motion. Furthermore, designing an appropriate two-time (slow and fast) scale controller in the presence of uncertainties is considered in order to track the desired hub angular position and suppress vibrations of the arm simultaneously. For the so-called slow subsystem, a novel controller design is proposed as two different cases, with and without the presence of uncertainties in system dynamics are considered; and accordingly, a control law for tracking the desired path is introduced based on the idea of using the cross-term constructed Lyapunov function. For the fast subsystem, a pole placement technique is used to suppress vibration of the beam. The simulation results indicate notable effectiveness of the proposed controller.

Synthesis, molecular docking, antimicrobial, antiquorum-sensing and antiproliferative activities of new series of pyrazolo[3,4-b]pyridine analogs

New series of pyrazolo[3,4-b]pyridines were prepared and evaluated for antimicrobial activity toward six selected microorganisms. Compounds 2a, 3b, 3d and 3e exhibited good activity toward B. cereus. On the other hand, 2a and 3b evinced interesting activity over C. albicans, whereas 2a, 3b and 3e displayed promising activity over A. fumigatus. Antiquorum-sensing effectiveness of the new members over C. violaceum was also assessed, where compounds 2a and 3b exhibited higher activity than that of the reference compound, indole. In vitro antiproliferative assessment toward HepG2, HCT-116 and MCF-7 cancer cells evidenced that 2f has notable effectiveness on all examined cell lines, whereas 3a–c were active but to a lower extent. In vivo antitumor activity of 2f and 3a–c against EAC cells was also esteemed, where 2f and 3c showed considerable activity comparable to that of doxorubicin. Cytotoxicity screening over WI38 and WISH normal cells evinced that 2f and 3a–c are less cytotoxic than doxorubicin. Compounds 2a, 2f, 3a–c and 3e were evaluated for DNA-binding affinity and topoisomerase IIβ inhibitory activity. Analogs 2a, 2f, 3a and 3b illustrated strong DNA-binding affinity, whereas 2a, 2f and 3a exhibited interesting topoisomerase IIβ inhibitory activity. Compounds 2a and 2f were docked into topoisomerase IIβ, where 2f showed preferential binding to topoisomerase IIβ. Computational studies articulated that the new members are in compliance with Veber's standards and Lipinski’s rule.

Addressing Fairness Issues in the Carbon Tax Law: The Case of British Columbia, Canada

The effects on the environment as a consequence of climate change are severe, especially the problem causing from anthropogenic greenhouse gas emissions. It is necessary to internalize these external costs caused by human activities. Taxes should be levied on polluters so as to reduce pollutions. Thus, accompanying with appropriate complementary measures and policies, carbon taxes are effective to mitigate emissions of CO2. Meanwhile, the carbon tax system in British Columbia, Canada achieves notable effectiveness, is worth further studying and analyzing, and can become a model for Taiwan.

Silica/quercetin sol–gel hybrids as antioxidant dental implant materials

The development of biomaterials with intrinsic antioxidant properties could represent a valuable strategy for preventing the onset of peri-implant diseases. In this context, quercetin, a naturally occurring flavonoid, has been entrapped at different weight percentages in a silica-based inorganic material by a sol–gel route. The establishment of hydrogen bond interactions between the flavonol and the solid matrix was ascertained by Fourier transform infrared spectroscopy. This technique also evidenced changes in the stretching frequencies of the quercetin dienonic moiety, suggesting that the formation of a secondary product occurs. Scanning electron microscopy was applied to detect the morphology of the synthesized materials. Their bioactivity was shown by the formation of a hydroxyapatite layer on sample surface soaked in a fluid that simulates the composition of human blood plasma. When the potential release of flavonol was determined by liquid chromatography coupled with ultraviolet and electrospray ionization tandem mass spectrometry techniques, the eluates displayed a retention time that was 0.5 min less than quercetin. Collision-activated dissociation mass spectrometry and untraviolet-visible spectroscopy were in accordance with the release of a quercetin derivative. The antiradical properties of the investigated systems were evaluated by DPPH and ABTS methods, whereas the 2,7-dichlorofluorescein diacetate assay highlighted their ability to inhibit the H2O2-induced intracellular production of reactive oxygen species in NIH-3T3 mouse fibroblast cells. Data obtained, along with data gathered from the MTT cytotoxicity test, revealed that the materials that entrapped the highest amount of quercetin showed notable antioxidant effectiveness.

Evaluation of the Effects of Homologous Platelet Gel on Healing Lower Extremity Wounds in Patients With Diabetes

The treatment of chronic diabetic wounds remains complicated, despite new insight into the cellular and molecular basis of wound healing and cutaneous regeneration. A growing body of clinical trials has shown that platelet release has a notable effectiveness on refractory ulcer healing. However, patients with chronic diabetic ulcers usually have poor general health, and the large-volume blood absence required to produce autologous platelet-rich plasma often causes adverse effects. To overcome the limitation, the homologous platelet gel (PG) from healthy donor was used for the treatment of chronic diabetic lower extremity wound in the study. We show here that homologous derived platelets significantly enhanced EVC304 cell and HaCaT cell proliferation and homologous PG was capable of prompting cell migration. Twenty-one patients with refractory diabetic lower extremity ulcers, who had no response to conventional treatments, were treated in this study. Our data indicated that homologous PG was effective for the enhancement and acceleration of diabetic lower extremity wounds healing. We propose that homologous PG appeared to enhance vascularization and epithelialization, which might induce a quicker healing process and and encourage controlled studies in future.

Dynamic modeling and adaptive vibration control study for giant magnetostrictive actuators

Giant magnetostrictive actuators (GMA) used in vibration control and high precision positioning control have been studied widely in last decade. Recently, although many researchers commit themselves to modeling giant magnetostrictive actuators, there is still lack of simplified model of analyzing nonlinear properties to deal with the problems on active vibration control with giant magnetostrictive actuators. In this paper, a nonlinear constitutive model of a giant magnetostrictive actuator is put forward for the application of effectively suppressing vibration. The nonlinear constitutive model is established not only by combining linear constitutive equations with the Bouc–Wen equations but also by using Hamilton's principle and the assumed mode method to analyze the hysteresis phenomena and quadric frequency property in the giant magnetostrictive actuator. In addition, a minimum variance self-turning regulator (MVSTR) is incorporated into the design of a controller, which may be used in suppressing low frequency (≤5Hz) and micron-level (≤5μm) disturbances. In the end of this paper, some simulations are performed in LABVIEW and experimental control tests are implemented using a giant magnetostrictive actuator prototype. Both the numerical simulations and experimental tests results show that the amplitudes of disturbances may be reduced up to no less than 90% averagely in the whole sampling processes. This proves that the giant magnetostrictive actuator has not only the capacity of controlling low-frequency and micro-level vibration but also the notable effectiveness of active control by the adaptive regulator. Moreover, the minimum variance self-tuning regulator is testified as a feasible controller for vibration control in the paper.

Efficient Strengthening Technique to Increase the Flexural Resistance of Existing RC Slabs

Composite materials are being used with notable effectiveness to increase and upgrade the flexural load carrying capacity of reinforced concrete (RC) members. Near-surface mounted (NSM) is one of the most promising strengthening techniques, based on the use of carbon fiber-reinforced polymer (CFRP) laminates. According to NSM, the laminates are fixed with epoxy based adhesive into slits opened into the concrete cover on the tension face of the elements to strength. Laboratory tests have shown that the NSM technique is an adequate strengthening strategy to increase the flexural resistance of RC slabs. However, in RC slabs of low concrete strength, the increase of the flexural resistance that NSM can provide is limited by the maximum allowable compressive strain in the compressed part of the slab, in order to avoid concrete crushing. This restriction reduces the effectiveness of the strengthening, thus limiting the use of the NSM technique. A new thin layer of concrete bonded to the existing concrete at the...

Industrial Practice of BiPCI Process of Pulverized Coal Injection for Blast Furnace Ironmaking at SSAB

BiPCI technology of pulverized coal injection for blast furnace ironmaking was applied to No.2 Blast Furnace of SSAB Oxelösund in Sweden, and notable effectiveness of this BiPCI practice at SSAB has been achieved. The results show that if the tuyere injection rate of pulverized coal is kept nearly unchanged, (1) BiPCI can increase the overall coal rate and decrease the coke rate. When the second injection rate of pulverized coal attains 5 kg/tHM, the coke rate could be reduced by 5 kg/tHM; (2) BiPCI can increase the burden permeability, decrease the pressure drop of the furnace, and produce proper gas flow distribution, which is favourable to keep smooth running of the blast furnace and decrease the total reducing agent rate (RAR). During the test, the RAR showed a decrease by 2.8 kg/tHM (corrected RAR by 1.45 kg/tHM); (3) The pulverized coal through the second injection can be effectively used to protect the coke from fast degradation and improve the coke strength in the blast furnace, which is favourable to lower the high requirement on the coke quality under high coal rate operation.

Waste gas emission control and constraints of energy and economy in China

This paper studies the characteristics of waste gas emission (WGE), energy consumption (EC) and economic development in China, and analyzes the reason for the change of waste gas intensity (WI) in order to provide necessary information for policy maker. Firstly, this paper describes the situation of WGE and the primary factors in China in general to describe the relationship among energy, economy and environmental at the national level. Then we detect the main sectors for WGE that have notable effectiveness for economic and EC through the comparison of the percentage of EC, value added (VA) and industrial WGE from combustion in 39 industrial sectors. Then with the calculation of energy intensity (EI), clean level (CL) and WI, this paper selects those crucial sectors for waste gas control and shows the efficiency of waste gas control in these sectors from 2001 to 2005. The result showed most waste gas came from heavy industrial sectors. However, heavy industrial sectors usually have lower CL than light industries. Moreover, within these sectors, some sectors, particularly Production and supply of electric power and heat power, showed the tendency of worsening efficiency for waste gas control from 2001 to 2005.

Water saving technology for paddy rice irrigation and its popularization in China

In consideration of the fact that drought occurs very often in China and the demand for paddy rice irrigation is very large, the technology of water saving irrigation for paddy rice is studied, and popularized in a demonstration region of the city of Yancheng. Test results show that dry-foot paddy irrigation saves 48.5% of water, and increases from 8.9 to 12.9% of yield, increasing 1302 Yaun of benefit per hectare, compared to traditional flooding irrigation. The technology has the advantages of clear index, notable effectiveness of water saving, reduction of soil loss and high production; besides, the rice is of good quality and the investment is economical. So, it is easy to be popularized in large areas.

Effectiveness of antioxidant‐impregnated film in retarding lipid oxidation

AbstractThe effectiveness of an antioxidant‐impregnated film to retard autoxidation of a packaged model product containing linoleic acid, via an evaporation/sorption mechanism, was evaluated as a function of storage time and temperature. The rate of loss of antioxidant from the package film structure was described by a first‐order expression. The first‐order rate constants were dependent on the initial concentration of antioxidant in the film. The rate of loss of 3,5‐di‐tert‐butyl‐4‐hydroxytoluene (BHT) from the package film structure was found to be much higher than the rate of loss of α‐tocopherol at both storage conditions (23 and 45 °C, 50% relative humidity) studied. A freeze‐dried model food product system was developed as the source for the autoxidation of linoleic acid in storage stability studies. The storage stability of this model food system packaged with antioxidant‐impregnated film pouches was evaluated. Hexanal as an index of oxidation from the model product system was collected by a dynamic purge and trap system and quantified by a gas chromatography/mass spectrometry procedure. The BHT‐impregnated laminate pouch showed a notable effectiveness in retarding lipid oxidation of the model product at 45 °C as a function of storage time. The control (non‐antioxidant) and α‐tocopherol‐impregnated laminate pouch structures showed no effect on retarding lipid oxidation of the model product during storage at 45 °C. Copyright © 2004 Society of Chemical Industry

Metronidazole. A therapeutic review and update.

The nitroimidazole antibiotic metronidazole has a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. Metronidazole has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, for which the drug was first approved as an effective treatment. Anaerobic bacteria which are typically sensitive are primarily Gram-negative anaerobes belonging to the Bacteroides and Fusobacterium spp. Gram-positive anaerobes such as peptostreptococci and Clostridia spp. are likely to test sensitive to metronidazole, but resistant isolates are probably encountered with greater frequency than with the Gram-negative anaerobes. Gardnerella vaginalis is a pleomorphic Gram-variable bacterial bacillus that is also susceptible to metronidazole. Helicobacter pylori has been strongly associated with gastritis and duodenal ulcers. Classic regimens for eradicating this pathogen have included metronidazole, usually with acid suppression medication plus bismuth and amoxicillin. The activity of metronidazole against anaerobic bowel flora has been used for prophylaxis and treatment of patients with Crohn's disease who might develop an infectious complication. Treatment of Clostridium difficile-induced pseudomembraneous colitis has usually been with oral metronidazole or vancomycin, but the lower cost and similar efficacy of metronidazole, coupled with the increased concern about imprudent use of vancomycin leading to increased resistance in enterococci, have made metronidazole the preferred agent here. Metronidazole has played an important role in anaerobic-related infections. Advantages to using metronidazole are the percentage of sensitive Gram-negative anaerobes, its availability as oral and intravenous dosage forms, its rapid bacterial killing, its good tissue penetration, its considerably lower chance of inducing C. difficile colitis, and expense. Metronidazole has notable effectiveness in treating anaerobic brain abscesses. Metronidazole is a cost-effective agent due to its low acquisition cost, its pharmacokinetics and pharmacodynamics, an acceptable adverse effect profile, and its undiminished antimicrobial activity. While its role as part of a therapeutic regimen for treating mixed aerobic/anaerobic infections has been reduced by newer, more expensive combination therapies, these new combinations have not been shown to have any therapeutic advantage over metronidazole. Although the use of metronidazole on a global scale has been curtailed by newer agents for various infections, metronidazole still has a role for these and other therapeutic uses. Many clinicians still consider metronidazole to be the 'gold standard' antibiotic against which all other antibiotics with anaerobic activity should be compared.

Linkages between biological and cultural diversity for participatory management: Nepal’s experiences with Makulu-Barun National park and its buffer zone

The Makalu-Barun National Park (MBNP) and its Buffer Zone (BZ) of eqastern Nepal shares is borders with Sagarmatha National Park on the west and with the Qomolongma Natural Preserve of the Tibet Autonomous Region of China on the North. The Park is rich in cultural diversity with many ethnic groups. Most of the households are economically poor and depend on subsistence agriculture, animal husbandry and diverse natural resources for livelihoods. Slash and burn cultivation on steep slopes, poaching, hunting, over grazing, high dependency on natural resources, poverty and food deficits are the main threats to biodiversity in MBNP and BZ area. The MBNP was established in 1991 while its BZ was declared in 1998. the basic underlying approach of protection and management of the Park and its BZ is biodiversity conservation through people participation, without relying on military force.
 
 This paper highlights the implementation of the biodiversity conservation and management approaches through people participation in the MBNP and its BZ, and also explores notable achievements and effectiveness of partnership of the Government of Nepal, the Mountain Institute (TMI) – an INGO and the local communities to sustain conservation efforts as well as to improve local livelihoods.
 
 Key words: Biodiversity; National Park; Buffer Zone; participation; culture; linkages
 
 Banko Janakari Vol.16(2) 2006 pp.37-44