More than 10 years survival with sequential therapy in a patient with advanced renal cell carcinoma: a case report

Although radical nephrectomy alone is widely accepted as the standard of care in localized treatment for renal cell carcinoma (RCC), it is not sufficient for the treatment of metastatic RCC (mRCC), which invariably leads to an unfavorable outcome despite the use of multiple therapies. Currently, sequential targeted agents are recommended for the management of mRCC, but the optimal drug sequence is still debated. This case was a 57-year-old man with clear-cell mRCC who received multiple therapies following his first operation in 2003 and has survived for over 10 years with a satisfactory quality of life. The treatments given included several surgeries, immunotherapy, and sequentially administered sorafenib, sunitinib, and everolimus regimens. In the course of mRCC treatment, well-planned surgeries, effective sequential targeted therapies and close follow-up are all of great importance for optimal management and a satisfactory outcome.

Scalable Feature Selection Applications for Genome-Wide Association Studies of Complex Diseases

Personalized medicine will revolutionize our capabilities to combat disease. Working toward this goal, a fundamental task is the deciphering of geneticvariants that are predictive of complex diseases. Modern studies, in the formof genome-wide association studies (GWAS) have afforded researchers with the opportunity to reveal new genotype-phenotype relationships through the extensive scanning of genetic variants. These studies typically contain over half a million genetic features for thousands of individuals. Examining this with methods other than univariate statistics is a challenging task requiring advanced algorithms that are scalable to the genome-wide level. In the future, next-generation sequencing studies (NGS) will contain an even larger number of common and rare variants. Machine learning-based feature selection algorithms have been shown to have the ability to effectively create predictive models for various genotype-phenotype relationships. This work explores the problem of selecting genetic variant subsets that are the most predictive of complex disease phenotypes through various feature selection methodologies, including filter, wrapper and embedded algorithms. The examined machine learning algorithms were demonstrated to not only be effective at predicting the disease phenotypes, but also doing so efficiently through the use of computational shortcuts. While much of the work was able to be run on high-end desktops, some work was further extended so that it could be implemented on parallel computers helping to assure that they will also scale to the NGS data sets. Further, these studies analyzed the relationships between various feature selection methods and demonstrated the need for careful testing when selecting an algorithm. It was shown that there is no universally optimal algorithm for variant selection in GWAS, but rather methodologies need to be selected based on the desired outcome, such as the number of features to be included in the prediction model. It was also demonstrated that without proper model validation, for example using nested cross-validation, the models can result in overly-optimistic prediction accuracies and decreased generalization ability. It is through the implementation and application of machine learning methods that one can extract predictive genotype–phenotype relationships and biological insights from genetic data sets.

Effects of sequential enzymatic hydrolysis on structural, bioactive and functional properties of Phaseolus lunatus protein isolate

Significant initiatives exist within the global food market to search for new, alternative protein sources with better technological, functional, and nutritional properties. Lima bean (Phaseolus lunatus L.) protein isolate was hydrolyzed using a sequential pepsin-pancreatin enzymatic system. Hydrolysis was performed to produce limited (LH) and extensive hydrolysate (EH), each with different degrees of hydrolysis (DH). The effects of hydrolysis were evaluated in vitro in both hydrolysates based on structural, functional and bioactive properties. Structural properties analyzed by electrophoretic profile indicated that LH showed residual structures very similar to protein isolate (PI), although composed of mixtures of polypeptides that increased hydrophobic surface and denaturation temperature. Functionality of LH was associated with amino acid composition and hydrophobic/hydrophilic balance, which increased solubility at values close to the isoelectric point. Foaming and emulsifying activity index values were also higher than those of PI. EH showed a structure composed of mixtures of polypeptides and peptides of low molecular weight, whose intrinsic hydrophobicity and amino acid profile values were associated with antioxidant capacity, as well as inhibiting angiotensin-converting enzyme. The results obtained indicated the potential of Phaseolus lunatus hydrolysates to be incorporated into foods to improve techno-functional properties and impart bioactive properties.

Review of investment strategy, portfolio management, and scorecard based portfolio selection tool for direct property investments in Finland

The lack of research of private real estate is a well-known problem. Earlier studies have mostly concentrated on the USA or the UK. Therefore, this master thesis offers more information about the performance and risk associated with private real estate investments in Nordic countries, but especially in Finland. The structure of this master thesis is divided into two independent sections based on the research questions. In first section, database analysis is performed to assess risk-return ratio of direct real estate investment for Nordic countries. Risk-return ratios are also assessed for different property sectors and economic regions. Finally, review of diversification strategies based on property sectors and economic regions is performed. However, standard deviation itself is not usually sufficient method to evaluate riskiness of private real estate. There is demand for more explicit assessment of property risk. One solution is property risk scoring. In second section risk scorecard based tool is built to make different real estate comparable in terms of risk. In order to do this, nine real estate professionals were interviewed to enhance the structure of theory-based risk scorecard and to assess weights for different risk factors.

Healthcare Information System Selection Model for Medical Clinics

The issue of selecting an appropriate healthcare information system is a very essential one. If implemented healthcare information system doesn’t fit particular healthcare institution, for example there are unnecessary functions; healthcare institution wastes its resources and its efficiency decreases. The purpose of this research is to develop a healthcare information system selection model to assist the decision-making process of choosing healthcare information system. Appropriate healthcare information system helps healthcare institutions to become more effective and efficient and keep up with the times. The research is based on comparison analysis of 50 healthcare information systems and 6 interviews with experts from St-Petersburg healthcare institutions that already have experience in healthcare information system utilization. 13 characteristics of healthcare information systems: 5 key and 7 additional features are identified and considered in the selection model development. Variables are used in the selection model in order to narrow the decision algorithm and to avoid duplication of brunches. The questions in the healthcare information systems selection model are designed to be easy-to-understand for common a decision-maker in healthcare institution without permanent establishment.

Design and Material Selection of High-Speed Rotating Electrical Machines

The increasing emphasis on energy efficiency is starting to yield results in the reduction in greenhouse gas emissions; however, the effort is still far from sufficient. Therefore, new technical solutions that will enhance the efficiency of power generation systems are required to maintain the sustainable growth rate, without spoiling the environment. A reduction in greenhouse gas emissions is only possible with new low-carbon technologies, which enable high efficiencies. The role of the rotating electrical machine development is significant in the reduction of global emissions. A high proportion of the produced and consumed electrical energy is related to electrical machines. One of the technical solutions that enables high system efficiency on both the energy production and consumption sides is high-speed electrical machines. This type of electrical machines has a high system overall efficiency, a small footprint, and a high power density compared with conventional machines. Therefore, high-speed electrical machines are favoured by the manufacturers producing, for example, microturbines, compressors, gas compression applications, and air blowers. High-speed machine technology is challenging from the design point of view, and a lot of research is in progress both in academia and industry regarding the solution development. The solid technical basis is of importance in order to make an impact in the industry considering the climate change. This work describes the multidisciplinary design principles and material development in high-speed electrical machines. First, high-speed permanent magnet synchronous machines with six slots, two poles, and tooth-coil windings are discussed in this doctoral dissertation. These machines have unique features, which help in solving rotordynamic problems and reducing the manufacturing costs. Second, the materials for the high-speed machines are discussed in this work. The materials are among the key limiting factors in electrical machines, and to overcome this limit, an in-depth analysis of the material properties and behavior is required. Moreover, high-speed machines are sometimes operating in a harsh environment because they need to be as close as possible to the rotating tool and fully exploit their advantages. This sets extra requirements for the materials applied.

Habitat selection of three rodents in a frequently burned boreal environment : productivity and habitat diversity

How does fire affect the plant and animal community of the boreal forest? This study attempted to examine the changes in plant composition and productivity, and small mammal demography brought about by fire in the northern boreal environment at Chick Lake, N.W.T. (65053fN, 128°14,W). Two 5*6 ha plots measuring 375m x 150m were selected for study during the summers of 1973 and 197^. One had been unburned for 120 years, the other was part of a fire which burned in the spring of 1969. Grids of 15m x 15m were established in each plot and meter square quadrats taken at each of the 250 grid intersections in order to determine plant composition and density. Aerial primary production was assessed by clipping and drying 80 samples of terminal new production for each species under investigation. Small mammal populations were sampled by placing a Sherman live trap at each grid intersection for ten days in every month. The two plots were similar in plant species composition which suggested that most regrowth in the burned area was from rootstocks which survived the fire. The plant data were submitted to a cluster analysis that revealed nine separate species associations, six of which occured in the burned area and eight of which occured in the control. These were subsequently treated as habitats for purposes of comparison with small mammal distributions. The burned area showed a greater productivity in flowers and fruits although total productivity in the control area was higher due to a large contribution from the non-vascular component. Maximum aerial productivity as dry wieght was measured at 157.1 g/m and 207.8 g/m for the burn and control respectively. Microtus pennsylvanicus and Clethrionomys rutilus were the two most common small mammals encountered; Microtus xanthognathus, Synaptomys borealis, and Phenacomys intermedius also occured in the area. Populations of M. pennsylvanicus and C. rutilus were high during the summer of 1973; however, M. pennsylvanicus was rare on the control but abundant on the burn, while C. rutilus was rare on the burn but abundant in the control. During the summer of 197^ populations declined, with the result that few voles of any species were caught in the burn while equal numbers of the two species were caught in the control. During the summer of 1973 M. pennsylvanicus showed a positive association to the most productive habitat type in the burn which was avoided by C. rutilus. In the control £• rutilus showed a similar positive association to the most productive habitat type which was avoided by M. pennsylvanicus. In all cases for the high population year of 1973# the two species never overlapped in habitat preference. When populations declined in 197^f "both species showed a strong association for the most productive habitat in the control. This would suggest that during a high population year, an abundant species can exclude competitors from a chosen habitat, but that this dominance decreases as population levels decrease. It is possible that M. pennsylvanicus is a more efficient competitor in a recently burned environment, while C. rutilus assumes this role once non-vascular regrowth becomes extensive.

A sequential analysis of therapist scaffolding and child concept formation in narrative therapy

Narrative therapy is a postmodern therapy that takes the position that people create self-narratives to make sense of their experiences. To date, narrative therapy has compiled virtually no quantitative and very little qualitative research, leaving gaps in almost all areas of process and outcome. White (2006a), one of the therapy's founders, has recently utilized Vygotsky's (1934/1987) theories of the zone of proximal development (ZPD) and concept formation to describe the process of change in narrative therapy with children. In collaboration with the child client, the narrative therapist formalizes therapeutic concepts and submits them to increasing levels of generalization to create a ZPD. This study sought to determine whether the child's development proceeds through the stages of concept formation over the course of a session, and whether therapists' utterances scaffold this movement. A sequential analysis was used due to its unique ability to measure dynamic processes in social interactions. Stages of concept formation and scaffolding were coded over time. A hierarchical log-linear analysis was performed on the sequential data to develop a model of therapist scaffolding and child concept development. This was intended to determine what patterns occur and whether the stated intent of narrative therapy matches its actual process. In accordance with narrative therapy theory, the log-linear analysis produced a final model with interactions between therapist and child utterances, and between both therapist and child utterances and time. Specifically, the child and youth participants in therapy tended to respond to therapist scaffolding at the corresponding level of concept formation. Both children and youth and therapists also tended to move away from earlier and toward later stages of White's scaffolding conversations map as the therapy session advanced. These findings provide support for White's contention that narrative therapists promote child development by scaffolding child concept formation in therapy.

Frequency-dependent selection at the amylase locus in Drosophila melanogaster

A. strain of Drosophila melanog-aster deficient in null amylase activity (Amylase ) was isolated from a wild null population of flies. The survivorship of Amylase homozygous flies is very low when the principal dietary carbohydrate source is starch. However, the survivorship of the null Amylase genotype is comparable to the wild type when the dietary starch is replaced by glucose. In addition, the null viability of the amylase-producing and Amylase strains is comparable v and very lm<] f on a medium with no carbohydrates . Furthermore, amylase-producing genotypes were shovm to excrete enzymatically active amylase protein into the food medium. The excreted amylase causes the external breakdown of dietary starch to sugar. These results led to the following null prediction: the viability of the A.mvlase genotype (fed on a starch rich diet) might increase in the presence of individuals which were amylase-producing. It was shown experimentally that such an increase in viability did in fact occur and that this increase v\Tas proportional to the number of mnylase..::producing fli.es present. These results provide a unique example of a non-"competi ti ve inter-genotype interaction, and one where the underlying physio~ logical and biochemical mechanism has been fully understood.