599 research outputs found
Impact of sex, MHC, and age of recipients on the therapeutic effect of transferred leukocytes from cancer-resistant SR/CR mice
<p>Abstract</p> <p>Background</p> <p>Spontaneous Regression/Complete Resistant (SR/CR) mice are resistant to cancer through a mechanism that is mediated entirely by leukocytes of innate immunity. Transfer of leukocytes from SR/CR mice can confer cancer resistance in wild-type (WT) recipients in both preventative and therapeutic settings. In the current studies, we investigated factors that may impact the efficacy and functionality of SR/CR donor leukocytes in recipients.</p> <p>Results</p> <p>In sex-mismatched transfers, functionality of female donor leukocytes was not affected in male recipients. In contrast, male donor leukocytes were greatly affected in the female recipients. In MHC-mismatches, recipients of different MHC backgrounds, or mice of different strains, showed a greater negative impact on donor leukocytes than sex-mismatches. The negative effects of sex-mismatch and MHC-mismatch on donor leukocytes were additive. Old donor leukocytes performed worse than young donor leukocytes in all settings including in young recipients. Young recipients were not able to revive the declining function of old donor leukocytes. However, the function of young donor leukocytes declined gradually in old recipients, suggesting that an aged environment may contain factors that are deleterious to cellular functions. The irradiation of donor leukocytes prior to transfers had a profound suppressive effect on donor leukocyte functions, possibly as a result of impaired transcription. The cryopreserving of donor leukocytes in liquid nitrogen had no apparent effect on donor leukocyte functions, except for a small loss of cell number after revival from freezing.</p> <p>Conclusion</p> <p>Despite the functional suppression of donor leukocytes in sex- and MHC-mismatched recipients, as well as old recipients, there was a therapeutic time period during the initial few weeks during which donor leukocytes were functional before their eventual rejection or functional decline. The eventual rejection of donor leukocytes will likely prevent donor leukocyte engraftment which would help minimize the risk of transfusion-associated graft-versus-host disease. Therefore, using leukocytes from healthy donors with high anti-cancer activity may be a feasible therapeutic concept for treating malignant diseases.</p
Gain and Loss Learning Differentially Contribute to Life Financial Outcomes
Emerging findings imply that distinct neurobehavioral systems process gains and losses. This study investigated whether individual differences in gain learning and loss learning might contribute to different life financial outcomes (i.e., assets versus debt). In a community sample of healthy adults (n = 75), rapid learners had smaller debt-to-asset ratios overall. More specific analyses, however, revealed that those who learned rapidly about gains had more assets, while those who learned rapidly about losses had less debt. These distinct associations remained strong even after controlling for potential cognitive (e.g., intelligence, memory, and risk preferences) and socioeconomic (e.g., age, sex, ethnicity, income, education) confounds. Self-reported measures of assets and debt were additionally validated with credit report data in a subset of subjects. These findings support the notion that different gain and loss learning systems may exert a cumulative influence on distinct life financial outcomes
Effectiveness of a smartphone app in increasing physical activity amongst male adults: a randomised controlled trial.
BACKGROUND: Smartphones are ideal for promoting physical activity in those with little intrinsic motivation for exercise. This study tested three hypotheses: H1 - receipt of social feedback generates higher step-counts than receipt of no feedback; H2 - receipt of social feedback generates higher step-counts than only receiving feedback on one's own walking; H3 - receipt of feedback on one's own walking generates higher step-counts than no feedback (H3). METHODS: A parallel group randomised controlled trial measured the impact of feedback on steps-counts. Healthy male participants (n = 165) aged 18-40 were given phones pre-installed with an app that recorded steps continuously, without the need for user activation. Participants carried these with them as their main phones for a two-week run-in and six-week trial. Randomisation was to three groups: no feedback (control); personal feedback on step-counts; group feedback comparing step-counts against those taken by others in their group. The primary outcome measure, steps per day, was assessed using longitudinal multilevel regression analysis. Control variables included attitude to physical activity and perceived barriers to physical activity. RESULTS: Fifty-five participants were allocated to each group; 152 completed the study and were included in the analysis: n = 49, no feedback; n = 53, individual feedback; n = 50, individual and social feedback. The study provided support for H1 and H3 but not H2. Receipt of either form of feedback explained 7.7 % of between-subject variability in step-count (F = 6.626, p < 0.0005). Compared to the control, the expected step-count for the individual feedback group was 60 % higher (effect on log step-count = 0.474, 95 % CI = 0.166-0.782) and that for the social feedback group, 69 % higher (effect on log step-count = 0.526, 95 % CI = 0.212-0.840). The difference between the two feedback groups (individual vs social feedback) was not statistically significant. CONCLUSIONS: Always-on smartphone apps that provide step-counts can increase physical activity in young to early-middle-aged men but the provision of social feedback has no apparent incremental impact. This approach may be particularly suitable for inactive people with low levels of physical activity; it should now be tested with this population
Business opportunities analysis using GIS: the retail distribution sector
[EN] The retail distribution sector is facing a difficult time as the current
landscape is characterized by ever-increasing competition. In these conditions, the
search for an appropriate location strategy has the potential to become a differentiating
and competitive factor. Although, in theory, an increasing level of importance
is placed on geography because of its key role in understanding the success of
a business, this is not the case in practice. For this reason, the process outlined in
this paper has been specifically developed to detect new business locations. The
methodology consists of a range of analyzes with Geographical Information Systems
(GISs) from a marketing point of view. This new approach is called geomarketing.
First, geodemand and geocompetition are located on two separate digital
maps using spatial and non-spatial databases. Second, a third map is obtained by
matching this information with the demand not dealt with properly by the current
commercial offer. Third, the Kernel density allows users to visualize results, thus
facilitating decision-making by managers, regardless of their professional background.
The advantage of this methodology is the capacity of GIS to handle large
amounts of information, both spatial and non-spatial. A practical application is
performed in Murcia (Spain) with 100 supermarkets and data at a city block level,
which is the highest possible level of detail. This detection process can be used in
any commercial distribution company, so it can be generalized and considered a
global solution for retailers.Roig Tierno, H.; Baviera-Puig, A.; Buitrago Vera, JM. (2013). Business opportunities analysis using GIS: the retail distribution sector. Global Business Perspectives. 1(3):226-238. doi:10.1007/s40196-013-0015-6S22623813Alarcón, S. (2011). The trade credit in the Spanish agrofood industry. Mediterranean Journal of Economics, Agriculture and Environment (New Medit), 10(2), 51–57.Alcaide, J. C., Calero, R., & Hernández, R. (2012). Geomarketing. Marketing territorial para vender y fidelizar más. Madrid: ESIC.Applebaum, W., & Cohen, S. B. (1961). The dynamics of store trading areas and market equilibrium. Annals of the Association of American Geographers, 51(1), 73–101.Baviera-Puig, A., Buitrago-Vera, J. M., Escriba, C., & Clemente, J. S. (2009). Geomarketing: Aplicación de los sistemas de información geográfica al marketing. Paper presented at the Octava Conferencia Iberoamericana en Sistemas, Cibernética e Informática, Orlando, FL.Baviera-Puig, A., Buitrago-Vera, J. M., & Mas-Verdú, F. (2012). Trade areas and knowledge-intensive services: The case of a technology centre. Management Decision, 50(8), 1412–1424.Baviera-Puig, A., Buitrago-Vera, J. M., & RodrÃguez-Barrio, J. E. (2013). Un modelo de geomarketing para la localización de supermercados: Diseño y aplicación práctica. Documentos de Trabajo de la Cátedra Fundación Ramón Areces de Distribución Comercial (DOCFRADIS), 1, 1–27.Berumen, S. A., & Llamazares, F. (2007). La utilidad los métodos de decisión multicriterio (como el AHP) en un entorno de competitividad creciente. Cuadernos de administración, 20(34), 65–87.Birkin, M., Clarke, G., & Clarke, M. (2002). Retail geography and intelligent network planning. Chichester: Wiley.Chasco, C. (2003). El geomarketing y la distribución commercial. Investigación y Márketing, 79, 6–13.Chen, R. J. C. (2007). Significance and variety of geographic information system (GIS) applications in retail, hospitality, tourism, and consumer services. Journal of Retailing and Consumer Services, 14, 247–248.Church, R. L. (2002). Geographical information systems and location science. Computers and Operations Research, 29, 541–562.Church, R. L., & Murray, A. T. (2009). Business site selection, location analysis and GIS. Hoboken, NJ: Wiley.Clarke, G. (1998). Changing methods of location planning for retail companies. GeoJournal, 45, 289–298.Clarkson, R. M., Clarke-Hill, C. M., & Robinson, T. (1996). UK supermarket location assessment. International Journal of Retail and Distribution Management, 24(6), 22–33.Davis, P. (2006). Spatial competition in retail markets: Movie theaters. The RAND Journal of Economics, 37(4), 964–982.Ghosh, A., & McLafferty, S. L. (1982). Locating stores in uncertain environments: A scenario planning approach. Journal of Retailing, 58(4), 5–22.Härdle, W. (1991). Smoothing techniques with implementation in S. Nueva York, NY: Springer.Harris, B., & Batty, M. (1993). Locational models, geographical information, and planning support systems. Journal of Planning Education and Research, 12, 184–198.Hernandez, T. (2007). Enhancing retail location decision support: The development and application of geovisualization. Journal of Retailing and Consumer Services, 14, 249–258.Hernandez, T., & Bennison, D. (2000). The art and science of retail location decisions. International Journal of Retail and Distribution Management, 28(8), 357–367.Huff, D. (1963). Defining and estimating a trade area. Journal of Marketing, 28, 34–38.Instituto Nacional de EstadÃstica (INE). (2011). Padrón de habitantes 2011. http://www.ine.es . Accessed 9 Oct 2012.Kelly, J. P., Freeman, D. C., & Emlen, J. M. (1993). Competitive impact model for site selection: The impact of competition, sales generators and own store cannibalization. The International Review of Retail, Distribution and Consumer Research, 3, 237–259.Latour, P., & Le Floc’h, J. (2001). Géomarketing: Principes, méthodes et applications. ParÃs: Éditions d’Organisation.Mendes, A. B., & Themido, I. H. (2004). Multi-outlet retail site location assessment. International Transactions in Operational Research, 11, 1–18.Moreno, A. (1991). Modelización cartográfica de densidades mediante estimadores Kernel. Treballs de la Societat Catalana de Geografia, 6(30), 155–170.Moreno, A. (2007). Obtención de capas raster de densidad. In A. Moreno (Coord.), Sistemas y Análisis de la información Geográfica. Manual de autoaprendizaje con ArcGIS (pp. 685–691). Madrid: Editorial RA-MA.Murad, A. A. (2003). Creating a GIS application for retail centers in Jeddah City. International Journal of Applied Earth Observation and Geoinformation, 4, 329–338.Murad, A. A. (2007). Using GIS for retail planning in Jeddah City. American Journal of Applied Sciences, 4(10), 820–826.Musyoka, S. M., Mutyauvyu, S. M., Kiema, J. B. K., Karanja, F. N., & Siriba, D. N. (2007). Market segmentation using geographic information systems (GIS). A case study of the soft drink industry in Kenya. Marketing Intelligence and Planning, 25(6), 632–642.Nielsen Database. (2012). Retailers Database. http://www.nielsen.com/global/en.html . Accessed 12 Oct 2012.Ozimec, A. M., Natter, M., & Reutterer, T. (2010). Geographical information systems-based marketing decisions: Effects of alternative visualizations on decision quality. Journal of Marketing, 74, 94–110.Reilly, W. J. (1931). The law of retail gravitation. New York: Knickerbocker Press.Rob, M. A. (2003). Some challenges of integrating spatial and non-spatial datasets using a geographical information system. Information Technology for Development, 10, 171–178.Rosenblatt, M. (1956). Remarks on some nonparametric estimates of a density functions. Annals of Mathematical Statistic, 27, 832–837.Sede Electrónica del Catastro. (2012). Datos Catastrales. https://www.sedecatastro.gob.es . Accessed 10 Oct 2012.Silverman, B. W. (1986). Density estimation for statistics and data analysis. London: Chapman and Hall.Sleight, P., Harris, R., & Webber, R. (2005). Geodemographics, GIS and neighbourhood targeting. Chichester: Wiley.Suárez-Vega, R., Santos-Peñate, D. R., & Dorta-González, P. (2012). Location models and GIS tools for retail site location. Applied Geography, 35, 12–22.Thaler, R. (1986). The psychology and economics conference handbook: Comments on Simon, on Einhorn and Hogarth, and on Tversky and Kahneman. The Journal of Business, 59(4), 279–284.Wood, S., & Reynolds, J. (2012). Leveraging locational insights within retail store development? Assessing the use of location planners’ knowledge in retail marketing. Geoforum, 43, 1076–1087
Key issues in the design of pay for performance programs
Pay for performance (P4P) is increasingly being used to stimulate healthcare providers to improve their performance. However, evidence on P4P effectiveness remains inconclusive. Flaws in program design may have contributed to this limited success. Based on a synthesis of relevant theoretical and empirical literature, this paper discusses key issues in P4P-program design. The analysis reveals that designing a fair and effective program is a complex undertaking. The following tentative conclusions are made: (1) performance is ideally defined broadly, provided that the set of measures remains comprehensible, (2) concerns that P4P encourages "selection" and "teaching to the test" should not be dismissed, (3) sophisticated risk adjustment is important, especially in outcome and resource use measures, (4) involving providers in program design is vital, (5) on balance, group incentives are preferred over individual incentives, (6) whether to use rewards or penalties is context-dependent, (7) payouts should be frequent and low-powered, (8) absolute targets are generally preferred over relative targets, (9) multiple targets are preferred over single targets, and (10) P4P should be a permanent component of provider compensation and is ideally "decoupled" form base payments. However, the design of P4P programs should be tailored to the specific setting of implementation, and empirical research is needed to confirm the conclusions
Long-Term Consumption of High-Fat Diet in Rats: Effects on Microglial and Astrocytic Morphology and Neuronal Nitric Oxide Synthase Expression
Average arterial input function for quantitative dynamic contrast enhanced magnetic resonance imaging of neck nodal metastases
Physical Analyses of E. coli Heteroduplex Recombination Products In Vivo: On the Prevalence of 5′ and 3′ Patches
BACKGROUND: Homologous recombination in Escherichia coli creates patches (non-crossovers) or splices (half crossovers), each of which may have associated heteroduplex DNA. Heteroduplex patches have recombinant DNA in one strand of the duplex, with parental flanking markers. Which DNA strand is exchanged in heteroduplex patches reflects the molecular mechanism of recombination. Several models for the mechanism of E. coli RecBCD-mediated recombinational double-strand-end (DSE) repair specify that only the 3'-ending strand invades the homologous DNA, forming heteroduplex in that strand. There is, however, in vivo evidence that patches are found in both strands. METHODOLOGY/PRINCIPLE FINDINGS: This paper re-examines heteroduplex-patch-strand polarity using phage lambda and the lambdadv plasmid as DNA substrates recombined via the E. coli RecBCD system in vivo. These DNAs are mutant for lambda recombination functions, including orf and rap, which were functional in previous studies. Heteroduplexes are isolated, separated on polyacrylamide gels, and quantified using Southern blots for heteroduplex analysis. This method reveals that heteroduplexes are still found in either 5' or 3' DNA strands in approximately equal amounts, even in the absence of orf and rap. Also observed is an independence of the RuvC Holliday-junction endonuclease on patch formation, and a slight but statistically significant alteration of patch polarity by recD mutation. CONCLUSIONS/SIGNIFICANCE: These results indicate that orf and rap did not contribute to the presence of patches, and imply that patches occurring in both DNA strands reflects the molecular mechanism of recombination in E. coli. Most importantly, the lack of a requirement for RuvC implies that endonucleolytic resolution of Holliday junctions is not necessary for heteroduplex-patch formation, contrary to predictions of all of the major previous models. This implies that patches are not an alternative resolution of the same intermediate that produces splices, and do not bear on models for splice formation. We consider two mechanisms that use DNA replication instead of endonucleolytic resolution for formation of heteroduplex patches in either DNA strand: synthesis-dependent-strand annealing and a strand-assimilation mechanism
Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state
A major challenge in neurobiology is to understand mechanisms underlying human neuronal diversification. Motor neurons (MNs) represent a diverse collection of neuronal subtypes, displaying differential vulnerability in different human neurodegenerative diseases. The ability to manipulate cell subtype diversification is critical to establish accurate, clinically relevant in vitro disease models. Retinoid signalling contributes to caudal precursor specification and subsequent MN subtype diversification. Here we investigate the necessity for retinoic acid in motor neurogenesis from human embryonic stem cells. We show that activin/nodal signalling inhibition, followed by sonic hedgehog agonist treatment, is sufficient for MN precursor specification, which occurs even in the presence of retinoid pathway antagonists. Importantly, precursors mature into HB9/ChAT-expressing functional MNs. Furthermore, retinoid-independent motor neurogenesis results in a ground state biased to caudal, medial motor columnar identities from which a greater retinoid-dependent diversity of MNs, including those of lateral motor columns, can be selectively derived in vitro
- …