874 resultados para Cost-to-Serve
Resumo:
We develop a framework for estimating the quality of transmission (QoT) of a new lightpath before it is established, as well as for calculating the expected degradation it will cause to existing lightpaths. The framework correlates the QoT metrics of established lightpaths, which are readily available from coherent optical receivers that can be extended to serve as optical performance monitors. Past similar studies used only space (routing) information and thus neglected spectrum, while they focused on oldgeneration noncoherent networks. The proposed framework accounts for correlation in both the space and spectrum domains and can be applied to both fixed-grid wavelength division multiplexing (WDM) and elastic optical networks. It is based on a graph transformation that exposes and models the interference between spectrum-neighboring channels. Our results indicate that our QoT estimates are very close to the actual performance data, that is, to having perfect knowledge of the physical layer. The proposed estimation framework is shown to provide up to 4 × 10-2 lower pre-forward error correction bit error ratio (BER) compared to theworst-case interference scenario,which overestimates the BER. The higher accuracy can be harvested when lightpaths are provisioned with low margins; our results showed up to 47% reduction in required regenerators, a substantial savings in equipment cost.
Resumo:
Human use of the oceans is increasingly in conflict with conservation of endangered species. Methods for managing the spatial and temporal placement of industries such as military, fishing, transportation and offshore energy, have historically been post hoc; i.e. the time and place of human activity is often already determined before assessment of environmental impacts. In this dissertation, I build robust species distribution models in two case study areas, US Atlantic (Best et al. 2012) and British Columbia (Best et al. 2015), predicting presence and abundance respectively, from scientific surveys. These models are then applied to novel decision frameworks for preemptively suggesting optimal placement of human activities in space and time to minimize ecological impacts: siting for offshore wind energy development, and routing ships to minimize risk of striking whales. Both decision frameworks relate the tradeoff between conservation risk and industry profit with synchronized variable and map views as online spatial decision support systems.
For siting offshore wind energy development (OWED) in the U.S. Atlantic (chapter 4), bird density maps are combined across species with weights of OWED sensitivity to collision and displacement and 10 km2 sites are compared against OWED profitability based on average annual wind speed at 90m hub heights and distance to transmission grid. A spatial decision support system enables toggling between the map and tradeoff plot views by site. A selected site can be inspected for sensitivity to a cetaceans throughout the year, so as to capture months of the year which minimize episodic impacts of pre-operational activities such as seismic airgun surveying and pile driving.
Routing ships to avoid whale strikes (chapter 5) can be similarly viewed as a tradeoff, but is a different problem spatially. A cumulative cost surface is generated from density surface maps and conservation status of cetaceans, before applying as a resistance surface to calculate least-cost routes between start and end locations, i.e. ports and entrance locations to study areas. Varying a multiplier to the cost surface enables calculation of multiple routes with different costs to conservation of cetaceans versus cost to transportation industry, measured as distance. Similar to the siting chapter, a spatial decisions support system enables toggling between the map and tradeoff plot view of proposed routes. The user can also input arbitrary start and end locations to calculate the tradeoff on the fly.
Essential to the input of these decision frameworks are distributions of the species. The two preceding chapters comprise species distribution models from two case study areas, U.S. Atlantic (chapter 2) and British Columbia (chapter 3), predicting presence and density, respectively. Although density is preferred to estimate potential biological removal, per Marine Mammal Protection Act requirements in the U.S., all the necessary parameters, especially distance and angle of observation, are less readily available across publicly mined datasets.
In the case of predicting cetacean presence in the U.S. Atlantic (chapter 2), I extracted datasets from the online OBIS-SEAMAP geo-database, and integrated scientific surveys conducted by ship (n=36) and aircraft (n=16), weighting a Generalized Additive Model by minutes surveyed within space-time grid cells to harmonize effort between the two survey platforms. For each of 16 cetacean species guilds, I predicted the probability of occurrence from static environmental variables (water depth, distance to shore, distance to continental shelf break) and time-varying conditions (monthly sea-surface temperature). To generate maps of presence vs. absence, Receiver Operator Characteristic (ROC) curves were used to define the optimal threshold that minimizes false positive and false negative error rates. I integrated model outputs, including tables (species in guilds, input surveys) and plots (fit of environmental variables, ROC curve), into an online spatial decision support system, allowing for easy navigation of models by taxon, region, season, and data provider.
For predicting cetacean density within the inner waters of British Columbia (chapter 3), I calculated density from systematic, line-transect marine mammal surveys over multiple years and seasons (summer 2004, 2005, 2008, and spring/autumn 2007) conducted by Raincoast Conservation Foundation. Abundance estimates were calculated using two different methods: Conventional Distance Sampling (CDS) and Density Surface Modelling (DSM). CDS generates a single density estimate for each stratum, whereas DSM explicitly models spatial variation and offers potential for greater precision by incorporating environmental predictors. Although DSM yields a more relevant product for the purposes of marine spatial planning, CDS has proven to be useful in cases where there are fewer observations available for seasonal and inter-annual comparison, particularly for the scarcely observed elephant seal. Abundance estimates are provided on a stratum-specific basis. Steller sea lions and harbour seals are further differentiated by ‘hauled out’ and ‘in water’. This analysis updates previous estimates (Williams & Thomas 2007) by including additional years of effort, providing greater spatial precision with the DSM method over CDS, novel reporting for spring and autumn seasons (rather than summer alone), and providing new abundance estimates for Steller sea lion and northern elephant seal. In addition to providing a baseline of marine mammal abundance and distribution, against which future changes can be compared, this information offers the opportunity to assess the risks posed to marine mammals by existing and emerging threats, such as fisheries bycatch, ship strikes, and increased oil spill and ocean noise issues associated with increases of container ship and oil tanker traffic in British Columbia’s continental shelf waters.
Starting with marine animal observations at specific coordinates and times, I combine these data with environmental data, often satellite derived, to produce seascape predictions generalizable in space and time. These habitat-based models enable prediction of encounter rates and, in the case of density surface models, abundance that can then be applied to management scenarios. Specific human activities, OWED and shipping, are then compared within a tradeoff decision support framework, enabling interchangeable map and tradeoff plot views. These products make complex processes transparent for gaming conservation, industry and stakeholders towards optimal marine spatial management, fundamental to the tenets of marine spatial planning, ecosystem-based management and dynamic ocean management.
Contributions of Dorsal/Ventral Hippocampus and Dorsolateral/Dorsomedial Striatum to Interval Timing
Resumo:
Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.
Resumo:
If a church reflects its larger community, it will have more dynamic interactions among different people. Current U.S. communities consist of very diverse people who have different socioeconomic and cultural backgrounds. Since the mid 20th century, various immigrant communities who have dissimilar cultural, religious, and linguistic traditions have accelerated the need of change in American churches. The drastic cultural change has demanded churches to equip their lay and clergy leaders with multicultural competencies for effective ministries.
My thesis explores imaginative leadership in cultural crossroads. Emphasizing the leadership imagination of cross-cultural ministry, I approach it in biblical, theological, and missional perspectives. In this dynamic cultural milieu, the study topic may help the church renew its ecclesial purpose by seeing cross-cultural ministry as a creative opportunity to reach out to more diverse people of God. I begin with a conceptual framework for cross-cultural ministry and cultural intelligence. Then I explain why cross-cultural ministry is significant and how it enhances the spirit of Christ Jesus. As I develop the thesis, I discuss leadership challenge and development in the cross-cultural ministry context. This thesis may contribute to equipping lay and clergy leaders by overcoming the homogeneous ‘in-group’ mindset in the church.
The primary focus is on developing marginal leadership of church in the post-Christendom era. Church leaders must creatively hold the tension between the current church context and Christian faith resources and seek a hopeful resolution as a third way through integrative thought process. While conventional leadership emphasizes a better choice out of the given options, marginal leadership takes time for integrative thought process to seek a new direction for the future. Conventional leaders take the center with their power, status, and prestige, but marginal leaders position themselves on the edge. Leading from the edge is a distinctive cross-cultural leadership and is based on the servant leadership of Jesus Christ who put himself as a servant for the marginalized. By serving and relating to others on the margin, this imaginative leadership may make appropriate changes desired in today’s American churches.
In addition to academic research, I looked into the realities of cross-cultural leadership in the local churches through congregational studies. I speculated that church leadership involves both laity and clergy and that it can be enhanced. All Christians are called to serve the Lord according to their gifts, and it is crucial for lay and clergy persons to develop their leadership character and skills. In particular, as humans are contextualized with their own cultures, church leaders often confront great challenges in cross-cultural or multicultural situations. Through critical thoughts and imaginative leadership strategies, however, they can overcome intrinsic human prejudice and obstacles.
Through the thesis project, I have reached four significant conclusions. First, cultural intelligence is an essential leadership capacity for all church leaders. As the church consists of more diverse cultural people today, its leaders need to have cultural competencies. In particular, cross-cultural leaders must be equipped with cultural intelligence. Cross-cultural ministry is not a simple byproduct of social change, but a creative strategy to open a door to bring God’s reconciliation among diverse people. Accordingly, church leaders are to be well prepared to effectively cope with the challenges of cultural interactions. Second, both lay and clergy leaders’ imaginative leadership is crucial for leading the congregation. While conventional leadership puts an emphasis on selecting a better choice based on the principle of opportunity cost, imaginative leaders critically consider the present church situations and Christian faith values together in integrative thoughts and pursue a third way as the congregation’s future hope. Third, cross-cultural leadership has a unique characteristic of leading from the edge and promotes God’s justice and peaceable relationships among different people. By leading the congregation from the edge, church leaders may experience the heart of Christ Jesus who became the friend of the marginalized. Fourth, the ‘homogeneous unit principle’ theory has its limit for today’s complex ‘inter-group’ community context. The church must be a welcoming and embracing faith community for all people. Cross-cultural ministry may become an entrance door for a more peaceable and reconciling life among different people. By building solidarity with others, the church may experience a kingdom reality.
This thesis focuses on the mission of the church and marginal leadership of church leaders in ever-changing cultural crossroads. The church becomes a hope in the broken and apathetic world, and Christians are called to build relationships inside and beyond the church. It is significant for church leaders to be faithfully present on the margin and relate to diverse people. By consistently positioning themselves on the margin, they can build relationships with new and diverse people and shape a faithful life pattern for others.
Resumo:
What constitutes effective corporate governance? Which director characteristics render boards effective at positively influencing firm-level performance outcomes? This dissertation examines these questions by taking a multilevel, multidisciplinary approach to corporate governance. I explore the individual-, team-, and firm- level factors that enable directors to serve effectively as strategic resources during international expansion. I argue that directors’ international experience improves their ability to serve as effective strategic consultants and resource providers to firms during the complex internationalization process. However, unlike prior research, which tends to assume that directors with the potential to provide important resources uniformly do so, I acknowledge contextual factors (i.e. board cohesiveness, strategic relevance of directors’ experience) that affect their propensity to actually influence outcomes. I explore these issues in three essays: one review essay and two empirical essays. In the first empirical essay, I integrate resource dependence theory with insights from social-psychological research to explore the influence of board capital on firms’ cross-border M&A performance. Using a sample of cross-border M&As completed by S&P 500 firms from 2004-2009, I find evidence that directors’ depth of international experience is associated with superior pre-deal outcomes. This suggests that boards’ deep, market-specific knowledge is valuable during the target selection phase. I further find that directors’ breadth of international experience is associated with superior post-deal performance, suggesting that these directors’ global mindset helps firms in the post-M&A integration phase. I also find that these relationships are positively moderated by board cohesiveness, measured by boards’ internal social ties. In the second empirical essay, I explore the boundary conditions of international board capital by examining how the characteristics of firms’ internationalization strategy moderate the relationship between board capital and firm performance. Using a panel of 377 S&P 500 firms observed from 2004-2011, I find that boards’ depth of international experience and social capital are more important during early stages of internationalization, when firms tend to lack market knowledge and legitimacy in the host markets. On the other hand, I find that breadth of international experience has a stronger relationship with performance when firms’ have higher scope of internationalization, when information-processing demands are higher.
Resumo:
The real-time optimization of large-scale systems is a difficult problem due to the need for complex models involving uncertain parameters and the high computational cost of solving such problems by a decentralized approach. Extremum-seeking control (ESC) is a model-free real-time optimization technique which can estimate unknown parameters and can optimize nonlinear time-varying systems using only a measurement of the cost function to be minimized. In this thesis, we develop a distributed version of extremum-seeking control which allows large-scale systems to be optimized without models and with minimal computing power. First, we develop a continuous-time distributed extremum-seeking controller. It has three main components: consensus, parameter estimation, and optimization. The consensus provides each local controller with an estimate of the cost to be minimized, allowing them to coordinate their actions. Using this cost estimate, parameters for a local input-output model are estimated, and the cost is minimized by following a gradient descent based on the estimate of the gradient. Next, a similar distributed extremum-seeking controller is developed in discrete-time. Finally, we consider an interesting application of distributed ESC: formation control of high-altitude balloons for high-speed wireless internet. These balloons must be steered into a favourable formation where they are spread out over the Earth and provide coverage to the entire planet. Distributed ESC is applied to this problem, and is shown to be effective for a system of 1200 ballons subjected to realistic wind currents. The approach does not require a wind model and uses a cost function based on a Voronoi partition of the sphere. Distributed ESC is able to steer balloons from a few initial launch sites into a formation which provides coverage to the entire Earth and can maintain a similar formation as the balloons move with the wind around the Earth.
Resumo:
This paper explores the ways in which the construction of militarized masculinities in Cold War Canadian media reflected the hegemonic masculinities and broader social trends of the period. This paper focuses specifically on the recruiting materials produced for and by the Canadian Army between 1956 and 1959, the time of the Suez Canal Crisis and the beginnings of “Canadian peacekeeping.” Through the mobilization of modern and anti-modern masculine identities attached to hegemonic and idealized Cold War Canadian masculinities, the Army created the image of the “Modern Warrior” to portray itself as an occupation and culture for “real Canadian men.” This identity simultaneously corresponded with Canada’s new “peacekeeping” identity. By presenting certain images of Canadian manhood as the “ideal” Canadian identity and by associating this “ideal” masculinity with military service, the Army’s recruitment advertisements conflated Cold War rhetoric of service, defence, national citizenship, cultural belonging, and “ideal” ethnicity with a Canadian identity available only to a specific (and often exclusive) segment of society. Because military service has long been considered the crux of citizenship, these advertisements (re)entrenched patterns of middle-class, heterosexual, Anglo- Saxon masculine power and dominance in a time of social uncertainty and cultural anxiety through the reaffirmation of this group’s “privilege” to serve the nation.
Resumo:
The provision of physical and social infrastructure in the form of roads, green spaces and community facilities has traditionally been provided for by the state through the general taxation system. However, as the state has been transformed along more neoliberal lines, the private sector is increasingly relied upon to deliver public goods and services. Planning gain agreements have flourished within this context by offering another vehicle through which local facilities are privately funded. Whilst these agreements reflect the broader dynamics of neoliberalism, they are commonly viewed as a tool which can be employed to challenge these very dynamics by empowering local communities to secure more just planning outcomes. This paper counters such claims. Based on evidence gathered from 80 interviews with planners, councillors, developers and community groups in Ireland, the paper demonstrates how planning gain agreements have been strategically redeployed by the holders of political and economic power to serve their own ends. In seeking to understand why and how this has occurred, specific consideration is given to the changing power dynamics between the state and private capital under neoliberalism. The paper highlights how institutional arrangements have enabled developers to infiltrate the political sphere in more subtle and implicit ways than ever before. We conclude by arguing that planning gain must be understood as a mechanism which has been manipulated in ways which essentially work to preserve and enhance, rather than redress, existing power imbalances in the planning system by facilitating large scale transfers of wealth upwards in society.
Resumo:
In this talk, I will describe various computational modelling and data mining solutions that form the basis of how the office of Deputy Head of Department (Resources) works to serve you. These include lessons I learn about, and from, optimisation issues in resource allocation, uncertainty analysis on league tables, modelling the process of winning external grants, and lessons we learn from student satisfaction surveys, some of which I have attempted to inject into our planning processes.
Resumo:
As neuroscience gains social traction and entices media attention, the notion that education has much to benefit from brain research becomes increasingly popular. However, it has been argued that the fundamental bridge toward education is cognitive psychology, not neuroscience. We discuss four specific cases in which neuroscience synergizes with other disciplines to serve education, ranging from very general physiological aspects of human learning such as nutrition, exercise and sleep, to brain architectures that shape the way we acquire language and reading, and neuroscience tools that increasingly allow the early detection of cognitive deficits, especially in preverbal infants. Neuroscience methods, tools and theoretical frameworks have broadened our understanding of the mind in a way that is highly relevant to educational practice. Although the bridge’s cement is still fresh, we argue why it is prime time to march over it.
Resumo:
This paper examines whether restaurant reservations should be locked to specific tables at the time the reservation is made, or whether the reservations should be pooled and assigned to tables in real-time. In two motivating studies, we find that there is a lack of consensus in the restaurant industry on handling reservations. Contrary to what might be expected based on research that shows the benefits of resource pooling in other contexts, a survey of 425 restaurants indicated that over 80% lock reservations to tables. In two simulation studies, we determine that pooling reservations enables a 15-minute reduction in table turn times more than 15% of the time, which consequently increases service efficiency and enables a restaurant to serve more customers during peak periods. Pooling had the most consistent advantage with higher customer service levels, with larger restaurants, with customers who arrive late, and with larger variation in customer arrival time.
Resumo:
Resource allocation decisions are made to serve the current emergency without knowing which future emergency will be occurring. Different ordered combinations of emergencies result in different performance outcomes. Even though future decisions can be anticipated with scenarios, previous models follow an assumption that events over a time interval are independent. This dissertation follows an assumption that events are interdependent, because speed reduction and rubbernecking due to an initial incident provoke secondary incidents. The misconception that secondary incidents are not common has resulted in overlooking a look-ahead concept. This dissertation is a pioneer in relaxing the structural assumptions of independency during the assignment of emergency vehicles. When an emergency is detected and a request arrives, an appropriate emergency vehicle is immediately dispatched. We provide tools for quantifying impacts based on fundamentals of incident occurrences through identification, prediction, and interpretation of secondary incidents. A proposed online dispatching model minimizes the cost of moving the next emergency unit, while making the response as close to optimal as possible. Using the look-ahead concept, the online model flexibly re-computes the solution, basing future decisions on present requests. We introduce various online dispatching strategies with visualization of the algorithms, and provide insights on their differences in behavior and solution quality. The experimental evidence indicates that the algorithm works well in practice. After having served a designated request, the available and/or remaining vehicles are relocated to a new base for the next emergency. System costs will be excessive if delay regarding dispatching decisions is ignored when relocating response units. This dissertation presents an integrated method with a principle of beginning with a location phase to manage initial incidents and progressing through a dispatching phase to manage the stochastic occurrence of next incidents. Previous studies used the frequency of independent incidents and ignored scenarios in which two incidents occurred within proximal regions and intervals. The proposed analytical model relaxes the structural assumptions of Poisson process (independent increments) and incorporates evolution of primary and secondary incident probabilities over time. The mathematical model overcomes several limiting assumptions of the previous models, such as no waiting-time, returning rule to original depot, and fixed depot. The temporal locations flexible with look-ahead are compared with current practice that locates units in depots based on Poisson theory. A linearization of the formulation is presented and an efficient heuristic algorithm is implemented to deal with a large-scale problem in real-time.
Resumo:
Inadequate final disposal of municipal solid waste (MSW) is associated with significant greenhouse gas (GHG) emission, environmental, health and safety issues, space consumption, public health and developmental issues in general. The environmental impact of waste is mostly felt in developing countries, inadequate waste management and treatment solution, inadequate policies and outdated practices are some of the factors leading to the significantly high final disposal of waste in dumps in developing countries. Brazil and other developing countries are changing the status quo by adopting polices that will adequately address this problem of inadequate waste management and disposal. Life cycle analysis (LCA) identifies the potential environmental impact of a product though environmental impact assessment, International Organization for Standardization (ISO) created the ISO 14040 and ISO 14044 to serve as principle guidelines for conducting LCA. Various waste treatment solution was applied to identify the waste management solution with the least Global warming potential (GWP) for treating the MSW generated from the city of Rio de Janerio, while reducing significantly final waste disposed in landfill.
Resumo:
The forensic toxicologist faces challenges in the detection of drugs and poisons in biological samples due to transformations which occur both during life and after death. For example, changes can result from drug metabolism during life or from the use of formalin solution for post mortem embalming purposes. The former requires the identification of drug metabolites and the latter the identification of chemical reaction products in order to know which substances had been administered. The work described in this thesis was aimed at providing ways of tackling these challenges and was divided into two parts. Part 1 investigated the use of in vitro drug metabolism by human liver microsomes (HLM) to obtain information on drug metabolites and Part 2 investigated the chemical reactions of drugs and a carbamate pesticide with formalin solution and formalin-blood. The initial aim of part I was to develop an in vitro metabolism method using HLM, based on a literature review of previous studies of this type. MDMA was chosen as a model compound to develop the HLM method because its metabolism was known and standards of its metabolites were commercially available. In addition, a sensitive and selective method was developed for the identification and quantitation of hydrophilic phase I drug metabolites using LC/MS/MS with a conventional reverse-phase (C18) column. In order to obtain suitable retention factors for polar drug metabolites on this column, acetyl derivatives were evaluated for converting the metabolites to more lipophilic compounds and an optimal separation system was developed. Acetate derivatives were found to be stable in the HPLC mobile phase and to provide good chromatographic separation of the target analytes. In vitro metabolism of MDMA and, subsequently, of other drugs involved incubation of 4 µg drug substance in pH 7.4 buffer with an NADPH generating system (NGS) at 37oC for 90 min with addition of more NGS after 30 min. The reaction was stopped at 90 min by the addition of acetonitrile before extraction of the metabolites. Acetate derivatives of MDMA metabolites were identified by LC/MS/MS using multiple reaction monitoring (MRM). Three phase I metabolites (both major and minor metabolites) of MDMA were detected in HLM samples. 3,4-dihydroxy-methamphetamine and 4-hydroxy-3-methoxymethamphetamine were found to be major metabolites of MDMA whereas 3,4-methylenedioxyamphetamine was found to be a minor metabolite. Subsequently, ten MDMA positive urines were analysed to compare the metabolite patterns with those produced by HLM. An LC/MS method for MDMA and its metabolites in urine samples was developed and validated. The method demonstrated good linearity, accuracy and precision and insignificant matrix effects, with limits of quantitation of 0.025 µg/ml. Moreover, derivatives of MDMA and its metabolites were quantified in all 10 positive human urine samples. The urine metabolite pattern was found to be similar to that from HLM. The second aim of Part 1 was to use the HLM system to study the metabolism of some new psychoactive substances, whose misuse worldwide has necessitated the development of analytical methods for these drugs in biological specimens. Methylone and butylone were selected as representative cathinones and para-methoxyamphetamine (PMA) was chosen as a representative ring-substituted amphetamine, because of the involvement of these drugs in recent drug-related deaths, because of a relative lack of information on their metabolism, and because reference standards of their metabolites were not commercially available. An LC/MS/MS method for the analysis of methylone, butylone, PMA and their metabolites was developed. Three phase I metabolites of methylone and butylone were detected in HLM samples. Ketone reduction to β-OH metabolites and demethylenation to dihydroxy-metabolites were found to be major phase I metabolic pathways of butylone and methylone whereas N-demethylation to nor-methylone and nor-butylone were found to be minor pathways. Also, demethylation to para-hydroxyamphetamine was found to be a major phase I metabolic pathway of PMA whereas β-hydroxylation to β-OH-PMA was found to be a minor pathway. Formaldehyde is used for embalming, to reduce decomposition and preserve cadavers, especially in tropical countries such as Thailand. Drugs present in the body can be exposed to formaldehyde resulting in decreasing concentrations of the original compounds and production of new substances. The aim of part II of the study was to evaluate the in vitro reactions of formaldehyde with selected drug groups including amphetamines (amphetamine, methamphetamine and MDMA), benzodiazepines (alprazolam and diazepam), opiates (morphine, hydromorphone, codeine and hydrocodone) and with a carbamate insecticide (carbosulfan). The study would identify degradation products to serve as markers for the parent compounds when these were no longer detectable. Drugs standards were spiked in 10% formalin solution and 10% formalin blood. Water and whole blood without formalin were used for controls. Samples were analysed by LC/MS/MS at different times from the start, over periods of up to 30 days. Amphetamine, methamphetamine and MDMA were found to rapidly convert to methamphetamine, DMA and MDDMA respectively, in both formalin solution and formalin blood, confirming the Eschweiler-Clarke reaction between amine-containing compounds and formaldehyde. Alprazolam was found to be unstable whereas diazepam was found to be stable in both formalin solution and water. Both were found to hydrolyse in formalin solution and to give open-ring alprazolam and open-ring diazepam. Other alprazolam conversion products attached to paraformaldehyde were detected in both formalin solution and formalin blood. Morphine and codeine were found to be more stable than hydromorphone and hydrocodone in formalin solution. Conversion products of hydromorphone and hydrocodone attached to paraformaldehyde were tentatively identified in formalin solution. Moreover, hydrocodone and hydromorphone rapidly decreased within 24 h in formalin blood and could not be detected after 7 days. Carbosulfan was found to be unstable in formalin solution and was rapidly hydrolysed within 24 h, whereas in water it was stable up to 48 h. Carbofuran was the major degradation product, plus smaller amounts of other products, 3-ketocarbofuran and 3-hydrocarbofuran. By contrast, carbosulfan slowly hydrolysed in formalin-blood and was still detected after 15 days. It was concluded that HLM provide a useful tool for human drug metabolism studies when ethical considerations preclude their controlled administration to humans. The use of chemical derivatisation for hydrophilic compounds such as polar drug metabolites for analysis by LC/MS/MS with a conventional C18 column is effective and inexpensive, and suitable for routine use in the identification and quantitation of drugs and their metabolites. The detection of parent drugs and their metabolites or conversion and decomposition products is potentially very useful for the interpretation of cases in forensic toxicology, especially when the original compounds cannot be observed.
Resumo:
As neuroscience gains social traction and entices media attention, the notion that education has much to benefit from brain research becomes increasingly popular. However, it has been argued that the fundamental bridge toward education is cognitive psychology, not neuroscience. We discuss four specific cases in which neuroscience synergizes with other disciplines to serve education, ranging from very general physiological aspects of human learning such as nutrition, exercise and sleep, to brain architectures that shape the way we acquire language and reading, and neuroscience tools that increasingly allow the early detection of cognitive deficits, especially in preverbal infants. Neuroscience methods, tools and theoretical frameworks have broadened our understanding of the mind in a way that is highly relevant to educational practice. Although the bridge’s cement is still fresh, we argue why it is prime time to march over it.