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Deuterium, the stable isotope of hydrogen, is known to medicinal chemists for its utility in mechanistic, spectroscopic, and tracer studies. In fact, wellknown applications utilizing deuterium exist within every subdiscipline in p...
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Deuterium, the stable isotope of hydrogen, is known to medicinal chemists for its utility in mechanistic, spectroscopic, and tracer studies. In fact, wellknown applications utilizing deuterium exist within every subdiscipline in pharmaceutical discovery and development. Recent emphasis on incorporation of deuterium into the active pharmaceutical ingredient has come about as a result of inquiries into the potential for substantial benefits of the deuterium kinetic isotope effect on the safety and disposition of the drug substance. This Perspective traces the author’s experience in reviving and expanding this potential utility, first suggested many decades prior by the discoverer of this, the simplest of all isotopes.
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Consumers have become increasingly aware of potential health benefits from diets rich in fruits and vegetables. While potato has not yet surfaced as a headline-grabber in this respect, there is increasing evidence that some genoty...
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Consumers have become increasingly aware of potential health benefits from diets rich in fruits and vegetables. While potato has not yet surfaced as a headline-grabber in this respect, there is increasing evidence that some genotypes may possess health attributes that warrant attention. Plant breeders rely on germplasm biodiversity to advance their programs and are also acutely aware of current marketing trends that relate to health attributes. Investigations of antioxidant properties for over 90 genotypes were conducted to characterize antioxidant profiles for the Colorado potato breeding program and to identify those especially rich in antioxidants. The objective was to summarize data based on total phenolics (TP), Trolox equivalent antioxidant capacity (TEAC) and vitamin C, as well as to provide LC/MS characterization of major phenolic compounds and glycoalkaloids for pigmented genotypes. Preliminary data from breast cancer cell culture inhibition studies were examined for relationships to in vitro chemical assays. Genotypes with red or purple skin and flesh consistently had the highest gallic acid equivalent TP, TEAC, and chlorogenic acid content. Baked tubers had lower TP levels, TEAC and vitamin C compared to uncooked, microwave cooked and boiled tubers. Environmental effects contributed year to year variation in TP and TEAC radical scavenging capacity. TP content increased after 6 to 7 months in refrigerated storage at 5 +/- 1 C in several highly pigmented, but not in white or yellow fleshed cultivars and selections. Major phenolic compounds, anthocyanins, and glycoalkaloid content were further investigated with LC/MS in six cultivars. The pigmented cultivars 'Purple Majesty' and 'Mountain Rose' contained considerably higher levels of chlorogenic acid isomers than the non-pigmented genotypes. In the non-pigmented genotypes, chlorogenic acid and glycolalkaloid content were highest in 'Rio Grande Russet'. Chlorogenic acid has been demonstrated to exhibit several desirable anticarcinogenic properties in recent biochemical investigations, as have several of the phenolic based anthocyanin pigments found in many colorful fruits and vegetables. Thus, comprehensive compositional profiles using LC/MS are of interest in characterizing germplasm for breeding purposes. Preliminary tests with phosphate buffered saline (PBS) extracts of baked tubers from six cultivars revealed that 'Rio Grande Russet' was most effective in inhibiting growth of breast cancer cultures MCF-7 and MDA-MB-468. 'Purple Majesty' inhibited to some extent, 'Mountain Rose' and 'Yukon Gold' had no inhibitory effect. A subsequent study with 21 genotypes where the initial extract was made with 80% acetone followed by drying and extraction in aqueous PBS differed from direct PBS extraction. Five genotypes including 'Russet Nugget' inhibited at 0.187% to 0.375% w/v of the cell culture solution. However, IC50 inhibition data was not strongly related to the in vitro chemical data for these cultivars.
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Objective Numerous problems exist with accessing prescription medicines in Australian Residential Aged Care Facilities (RACF). This research aimed to identify the issues surrounding a theoretical model for pharmacists' prescribing...
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Objective Numerous problems exist with accessing prescription medicines in Australian Residential Aged Care Facilities (RACF). This research aimed to identify the issues surrounding a theoretical model for pharmacists' prescribing in these facilities that had been proposed to address these problems. Specific objectives were to conceptually tailor the model to the RACF setting and qualitatively examine its potential applicability. Setting Data were collected from June to September 2004 via 34 semi-structured interviews with representatives of 28 stakeholder organisations, and 12 homogeneous focus groups comprising 25 consumers, 28 pharmacists and 18 medical practitioners representing rural and metropolitan locations. Participants were sourced from four states/territories of Australia. Method The so-called 'Medication Maintenance' model had previously been developed from the international literature and discussion with an expert steering committee. It proposes a system for pharmacists to continue Pharmaceutical Benefits Scheme prescriptions for patients whose therapy had been stabilised by a medical practitioner, by one month, one repeat or one original pack, as appropriate. The potential benefits, harms, barriers and facilitators were discussed with relevant stakeholders. Data were thematically analysed, and recommendations made for trial of the model. Key findings Potential benefits of the 'Medication Maintenance' model include improved patient focus, efficiency and interprofessional relationships. Potential harms include increased risk, possible wastage and exploitation. Potential barriers include role conflict, lack of controls, legislative issues and conflict of interest for pharmacists. Facilitators for the model were identified as defined roles and protocols, limitations on supply, regular patient review, communication channels and shared patient records. Conclusion A range of benefits, harms, barriers and facilitators of this theoretical model were elucidated from stakeholders. This has led tothe proposal of a staged implementation trial of the model, which should involve clinical, humanistic and economic outcome monitoring, and attitudi-nal, practical and legislative issues to be addressed.
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The potential for patch rather than blanket spraying of certain arable weeds has surprising benefits, as this research project shows. Silsoe and Rothamsted researchers, along with their commercial partners in the SAPPIO LINK proje...
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The potential for patch rather than blanket spraying of certain arable weeds has surprising benefits, as this research project shows. Silsoe and Rothamsted researchers, along with their commercial partners in the SAPPIO LINK project, have shown thatrelatively simple methods of mapping and spraying can be used to do the job, and that weed patches are sufficiently stable not to need re-mapping every year. "Many farmers already patch spray to an extent, in that they are aware of weedy areas within fields and turn their sprayer on and off accordingly," notes Peter Lutman of IACR Rothamsted. "We have been looking at ways of refining that approach by locating weed patches more accurately and using GPS technology to automatically control the sprayer." Principal targets are blackgrass, wild oats, couch grass, cleavers and perennial thistle, simply because they meet three key criteria: they occur in distinct patches; they are treated with specific herbicides; and the herbicides used are relatively expensive.
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A quantitative framework is presented dealing with competing opportunity and failure events in a finite time interval. The framework is based on the new fundamental concepts potential benefit, potential loss and potential gain, fo...
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A quantitative framework is presented dealing with competing opportunity and failure events in a finite time interval. The framework is based on the new fundamental concepts potential benefit, potential loss and potential gain, for which closed-form expressions regarding their distributions are derived and verified by a simulation. It is demonstrated that a decision strategy based on multiple event occurrences yields a very different gain compared with a decision strategy based on the next event occurrence. The results are illustrated by examples supporting decision making.
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BACKGROUND: N-of-1 trials may enhance therapeutic precision by predicting the long-term effectiveness of medical treatment on an individual basis. However, the n-of-1 approach has gained little traction with the clinical community...
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BACKGROUND: N-of-1 trials may enhance therapeutic precision by predicting the long-term effectiveness of medical treatment on an individual basis. However, the n-of-1 approach has gained little traction with the clinical community. To learn why, we interviewed physicians and patients, focusing on the perceived benefits and drawbacks of n-of-1 trials and factors influencing these perceptions. METHODS: We convened focus groups and individual interviews with 21 physicians and 32 patients, most with chronic conditions. The study employed qualitative interview methods to explore and analyze subjects' views of n-of-1 trials. Analysis involved an iterative process of review and data abstraction after specific topics for coding, definitions of codes, and strategies for abstraction had been established. Previously defined domains and topics were then expanded and enriched, with key themes emerging during the analytic process. RESULTS: Physicians and patients remarked on 4 salient aspects of n-of-1 trials: scientific, relational, clinical, and logistical. Neither physicians nor patients were highly familiar with the n-of-1 concept, but both groups readily grasped the fundamental logic and appreciated the potential scientific benefits. Physicians saw n-of-1 trials as promoting an exciting but possibly threatening paradigm shift in the doctor-patient relationship, while patients viewed the relational consequences as modest. The best n-of-1 candidates were felt to be proactive, cognitively intact, reliable, motivated, and engaged in a trusting physician-patient relationship. CONCLUSIONS: Researchers interested in expanding the appeal of n-of-1 trials will need to address these concerns by carefully explaining the approach, emphasizing the benefits, and minimizing the effort required of doctors and patients.
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BACKGROUND: N-of-1 trials may enhance therapeutic precision by predicting the long-term effectiveness of medical treatment on an individual basis. However, the n-of-1 approach has gained little traction with the clinical community...
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BACKGROUND: N-of-1 trials may enhance therapeutic precision by predicting the long-term effectiveness of medical treatment on an individual basis. However, the n-of-1 approach has gained little traction with the clinical community. To learn why, we interviewed physicians and patients, focusing on the perceived benefits and drawbacks of n-of-1 trials and factors influencing these perceptions. METHODS: We convened focus groups and individual interviews with 21 physicians and 32 patients, most with chronic conditions. The study employed qualitative interview methods to explore and analyze subjects' views of n-of-1 trials. Analysis involved an iterative process of review and data abstraction after specific topics for coding, definitions of codes, and strategies for abstraction had been established. Previously defined domains and topics were then expanded and enriched, with key themes emerging during the analytic process. RESULTS: Physicians and patients remarked on 4 salient aspects of n-of-1 trials: scientific, relational, clinical, and logistical. Neither physicians nor patients were highly familiar with the n-of-1 concept, but both groups readily grasped the fundamental logic and appreciated the potential scientific benefits. Physicians saw n-of-1 trials as promoting an exciting but possibly threatening paradigm shift in the doctor-patient relationship, while patients viewed the relational consequences as modest. The best n-of-1 candidates were felt to be proactive, cognitively intact, reliable, motivated, and engaged in a trusting physician-patient relationship. CONCLUSIONS: Researchers interested in expanding the appeal of n-of-1 trials will need to address these concerns by carefully explaining the approach, emphasizing the benefits, and minimizing the effort required of doctors and patients.
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Demographic trends project increasing numbers of older people to engage in exercise programs and sports. Sustained participation depends on both perceived health outcomes and avoidance of debilitating injuries. This review explore...
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Demographic trends project increasing numbers of older people to engage in exercise programs and sports. Sustained participation depends on both perceived health outcomes and avoidance of debilitating injuries. This review explores the potential benefits of physiologically based warm-up strategies to alleviate some key age-related decreases in the biomechanical capacity for skilled sport movements.
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This study develops an integrated model for dynamically predicting the energy potential of straw resources and assessing regional energy, environmental, and socioeconomic benefits of straw utilization for energy production. Jilin ...
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This study develops an integrated model for dynamically predicting the energy potential of straw resources and assessing regional energy, environmental, and socioeconomic benefits of straw utilization for energy production. Jilin Province, China is taken as an empirical study area. The quantity of straw resources is estimated by principal component analysis and autoregressive integrated moving average model considering panel data of six influential factors and grain yield. The regional energy, environmental, and socioeconomic benefits of straw utilization through three bioenergy conversion technologies (direct-combustion power generation, briquette fuel and cellulosic fuel ethanol) are quantitatively evaluated referring to Global Bioenergy Partnership's sustainability indicators. The results indicate that the quantity of straw available for energy production has continuous rising trend spanning 15 years (2016-2030) and could amount to 47.10 million t (Mt) by 2030. According to local government planning within 15 years, three straw-energy industries could contribute to a net profit of 2.2 billion USD. The accumulative mitigation amount of greenhouse gases, SO2, NOx and PM2.5 is 700.25 Mt, 3.99 Mt, 2.05 Mt and 3.94 Mt, respectively in contrast to fossil fuels burning and open-burning of straw. In total 166.05 thousand employments could be created. The methods and results presented are expected to provide decision makers with guidance for regional development of bioenergy industries. (C) 2018 Elsevier Ltd. All rights reserved.
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