Engineered gp120 immunogens that elicit VRC01-like antibodies by vaccination

Background: One of the great challenges for an HIV vaccine is to elicit broadly neutralizing antibodies specific for conserved epitopes from which the virus cannot easily escape. The CD4 binding site is one such epitope against which several antibodies (e.g. b12, VRC01) have been isolated. In macaques infected with SHIV, passive immunization with these CD4-directed neutralizing antibodies fails to control the virus, but prophylactic administration is highly protective. Similarly, patients who generate neutralizing antibodies over the course of an HIV infection derive no clinical benefit from them, but eliciting such antibodies prophylactically by vaccination may prevent the virus from establishing its lethal foothold

Stability and Change of Neuroticism in Aging

Data from the Longitudinal Aging Study Amsterdam were used to study the relationship between neuroticism and aging. At baseline, cross-sectional analyses of data from 2,117 respondents (aged 55–85 years, M = 70) showed no significant age differences. The magnitude of the 3- and 6-year stability coefficients was high, and 12% of the elderly participants showed a clinically relevant mean level change. Longitudinal multilevel analyses showed a small but statistical significant change with aging, but the mean change was not considered clinically relevant. A U-formed course was found, showing a slight decrease until respondents reached the age of 70. Adjusting the model for physical health-related variables slightly increased the stability. An additional interaction analysis showed that the individual trajectory of neuroticism was not affected by the physical health status. In conclusion, neuroticism remains rather stable in middle and older adulthood, with some apparent increase in late life

CBR model for the intelligent management of customer support centers

[EN] In this paper, a new CBR system for Technology Management Centers is presented. The system helps the staff of the centers to solve customer problems by finding solutions successfully applied to similar problems experienced in the past. This improves the satisfaction of customers and ensures a good reputation for the company who manages the center and thus, it may increase its profits. The CBR system is portable, flexible and multi-domain. It is implemented as a module of a help-desk application to make the CBR system as independent as possible of any change in the help-desk. Each phase of the reasoning cycle is implemented as a series of configurable plugins, making the CBR module easy to update and maintain. This system has been introduced and tested in a real Technology Management center ran by the Spanish company TISSAT S.A.Financial support from Spanish government under grant PROFIT FIT-340001-2004-11 is gratefully acknowledgeHeras Barberá, SM.; Garcia Pardo Gimenez De Los Galanes, JA.; Ramos-Garijo Font De Mora, R.; Palomares Chust, A.; Julian Inglada, VJ.; Rebollo Pedruelo, M.; Botti, V. (2006). CBR model for the intelligent management of customer support centers. En Lecture Notes in Computer Science. Springer Verlag (Germany). 663-670. https://doi.org/10.1007/11875581_80S663670Acorn, T., Walden, S.: SMART: SupportManagement Automated Reasoning Technology for Compaq Customer Service. In: Scott, A., Klahr, P. (eds.) Proceedings of the 2 International Conference on Intelligent Tutoring Systems, ITS-92 Berlin, vol. 4, pp. 3–18. AAAI Press, Menlo Park (1992)Simoudis, E.: Using Case-Based Retrieval for Customer Technical Support. IEEE Intelligent Systems 7, 10–12 (1992)Kriegsman, M., Barletta, R.: Building a Case-Based Help Desk Application. IEEE Expert: Intelligent Systems and Their Applications 8, 18–26 (1993)Shimazu, H., Shibata, A., Nihei, K.: Case-Based Retrieval Interface Adapted to Customer-Initiated Dialogues in Help Desk Operations. In: Mylopoulos, J., Reiter, R. (eds.) Proceedings of the 12th National Conference on Artificial Intelligence, vol. 1, pp. 513–518. AAAI Press, Menlo Park (1994)Raman, R., Chang, K.H., Carlisle, W.H., Cross, J.H.: A self-improving helpdesk service system using case-based reasoning techniques. Computers in Industry 2, 113–125 (1996)Kang, B.H., Yoshida, K., Motoda, H., Compton, P.: Help Desk System with Intelligent Interface. Applied Artificial Intelligence 11, 611–631 (1997)Roth-Berghofer, T., Iglezakis, I.: Developing an Integrated Multilevel Help-Desk Support System. In: Proceedings of the 8th German Workshop on Case-Based Reasoning, pp. 145–155 (2000)Goker, M., Roth-Berghofer, T.: The development and utilization of the case-based help-desk support system HOMER. Engineering Applications of Artificial Intelligence 12, 665–680 (1999)Roth-Berghofer, T.R.: Learning from HOMER, a case-based help-desk support system. In: Melnik, G., Holz, H. (eds.) Advances in Learning Software Organizations, pp. 88–97. Springer, Heidelberg (2004)Bergmann, R., Althoff, K.D., Breen, S., Göker, M., Manago, M., Traphöner, R., Wess, S.: Developing Industrial Case-Based Reasoning Applications. In: The INRECA Methodology, 2nd edn. LNCS (LNAI), vol. 1612. Springer, Heidelberg (2003)eGain (2006), http://www.egain.comKaidara Software Corporation (2006), http://www.kaidara.com/Empolis Knowledge Management GmbH - Arvato AG (2006), http://www.empolis.com/Althoff, K.D., Auriol, E., Barletta, R., Manago, M.: A Review of Industrial Case-Based Reasoning Tools. AI Perspectives Report. Goodall, A., Oxford (1995)Watson, I.: Applying Case-Based Reasoning. Techniques for Enterprise Systems. Morgan Kaufmann Publishers, Inc. California (1997)empolis: empolis Orenge Technology Whitepaper. Technical report, empolis GmbH (2002)Tissat, S.A. (2006), http://www.tissat.esGiraud-Carrier, C., Martinez, T.R.: An integrated framework for learning and reasoning. Journal of Artificial Intelligence Research 3, 147–185 (1995)Corchado, J.M., Borrajo, M.L., Pellicer, M.A., Yanez, J.C.: Neuro-symbolic system for Business Internal Control. In: Perner, P. (ed.) ICDM 2004. LNCS (LNAI), vol. 3275, pp. 1–10. Springer, Heidelberg (2004)Aamodt, A., Plaza, E.: Case-based reasoning: foundational issues, methodological variations and system approaches. AI Communications 7(1), 39–59 (1994)Tversky, A.: Features of similarity. Psychological Review 84(4), 327–352 (1997

Co-morbidity and visual acuity are risk factors for health-related quality of life decline: five-month follow-up EQ-5D data of visually impaired older patients

<p>Abstract</p> <p>Background</p> <p>Co-morbidity is a common phenomenon in the elderly and is considered to be a major threat to quality of life (QOL). Knowledge of co-existing conditions or patient characteristics that lead to an increased QOL decline is important for individual care, and for public health purposes. In visually impaired older adults, it remains unclear which co-existing conditions or other characteristics influence their health-related QOL. Our aim was to present a risk profile of characteristics and conditions which predict deterioration of QOL in visually impaired older patients.</p> <p>Methods</p> <p>Analyses were performed on data from an observational study among 296 visually impaired older patients from four Dutch hospitals. QOL was measured with the EuroQol-5D (EQ-5D) at baseline and at five-month follow-up. Nine co-existing condition categories (musculoskeletal; diabetes; heart; hypertension; chronic obstructive pulmonary disease (COPD) or asthma; hearing impairment; stroke; cancer; gastrointestinal conditions) and six patient characteristics (age; gender; visual acuity; social status; independent living; rehabilitation type) were tested in a linear regression model to determine the risk profile. The model was corrected for baseline EQ-5D scores. In addition, baseline EQ-5D scores were compared with reference scores from a younger visually impaired population and from elderly in the general population.</p> <p>Results</p> <p>From the 296 patients, 50 (16.9%) were lost to follow-up. Patients who reported diabetes, COPD or asthma, consequences of stroke, musculoskeletal conditions, cancer, gastrointestinal conditions or higher logMAR Visual Acuity values, experienced a lower QOL. After five months, visual acuity, musculoskeletal conditions, COPD/asthma and stroke predicted a decline in QOL (R²= 0.20). At baseline, the visually impaired older patients more often reported moderate or severe problems on most EQ-5D dimensions than the two reference groups.</p> <p>Conclusion</p> <p>In visually impaired older patients, visual acuity, musculoskeletal conditions, COPD/asthma and stroke predicted a relatively rapid decline in health-related QOL. With this risk profile, a specific referral by the ophthalmologist to another sub-specialty may have a beneficial effect on the patient's health-related QOL. A referral by the ophthalmologist or optometrist to a multidisciplinary rehabilitation service seems appropriate for some patients with co-morbidity. The current results need to be confirmed in studies using pre-structured questionnaires to assess co-morbidity.</p

Is there a U-shaped association between physical activity and falling in older persons?

Summary: This study tests whether the relationship between physical activity and (recurrent) falling is U-shaped. Among 1,337 community-dwelling older persons, no evidence for a nonlinear association was found. If all older persons increase their physical activity level with 100 units, 4% may be prevented to become recurrent fallers. Introduction: Previous studies suggest a U-shaped relationship between physical activity and falling. This study tests this hypothesis and examines whether this relationship is modified by level of physical functioning. Methods: Community-dwelling persons (65+) from the Longitudinal Aging Study Amsterdam (LASA) were prospectively followed on falls for 3 years after baseline assessment in 1995/1996 (n=1,337). Outcome measures were time to first fall and time to recurrent falling. The LASA Physical Activity Questionnaire was used to calculate physical activity in minutes per day weighted for intensity (range 0-2000). Physical functioning was measured with physical performance tests and self reported functional limitations. Confounders were age, sex, body mass index, chronic diseases, psychotropic medication, cognitive functioning, depressive symptoms, and fear of falling. Results: No evidence for a nonlinear association was found (p for physical activity > 0.20). No significant association was found between physical activity and time to first fall. An increase in physical activity of 100 units led to a 4% decrease in risk of recurrent falling (adjusted hazard ratio 0.96, 95% confidence interval 0.92, 0.99). No interactions with physical performance or functional limitations were found (p>0.50). Conclusions: The hypothesized U-shaped relationship between physical activity and falling could not be confirmed. At higher levels of physical activity, the risk of recurrent falling decreased, while no association was found with fall risk

Utilization of acute and long-term care in the last year of life: comparison with survivors in a population-based study

Background. It is well-known that the use of care services is most intensive in the last phase of life. However, so far only a few determinants of end-of-life care utilization are known. The aims of this study were to describe the utilization of acute and long-term care among older adults in their last year of life as compared to those not in their last year of life, and to examine which of a broad range of determinants can account for observed differences in care utilization. Methods. Data were used from the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified population-based cohort of 3107 persons aged 55 ? 85 years at baseline and representative of the Netherlands, follow-up cycles took place at 3, 6 and 9 years. Those who died within one year directly after a cycle were defined as the "end-of-life group" (n = 262), and those who survived at least three years after a cycle were defined as the "survivors". Utilization of acute and long-term care services, including professional and informal care, were recorded at each cycle, as well as a broad range of health-related and psychosocial variables. Results. The end-of-life group used more care than the survivors. In the younger-old this difference was most pronounced for acute care, and in the older-old, for long-term care. Use of both acute and long-term home care in the last year of life was fully accounted for by health problems. Use of institutional care at the end of life was partly accounted for by health problems, but was not fully explained by the determinants included. Conclusion. This study shows that severity of health problems are decisive in the explanation of the increase in use of care services towards the end-of-life. This information is essential for an appropriate allocation of professional health care to the benefit of older persons themselves and their informal caregivers. © 2009 Pot et al; licensee BioMed Central Ltd

Low Mid-Upper Arm Circumference, Calf Circumference, and Body Mass Index and Mortality in Older Persons

Background.Low body mass index is a general measure of thinness. However, its measurement can be cumbersome in older persons and other simple anthropometric measures may be more strongly associated with mortality. Therefore, associations of low mid-upper arm circumference, calf circumference, and body mass index with mortality were examined in older persons.Methods.Data of the Longitudinal Aging Study Amsterdam, a population-based cohort study in the Netherlands, were used. The present study included community-dwelling persons 65 years and older in 1992-1993 (n = 1,667), who were followed until 2007 for their vital status. Associations between anthropometric measures and 15-year mortality were examined by spline regression models and, below the nadir, Cox regression models, transforming all measures to sex-specific Z scores.Results.Mortality rates were 599 of 826 (73%) in men and 479 of 841 (57%) in women. Below the nadir, the hazard ratio of mortality per 1 standard deviation lower mid-upper arm circumference was 1.79 (95% confidence interval, 1.48-2.16) in men and 2.26 (1.71-3.00) in women. For calf circumference, the hazard ratio was 1.45 (1.22-1.71) in men and 1.30 (1.15-1.48) in women and for body mass index 1.38 (1.17-1.61) in men and 1.56 (1.10-2.21) in women. Excluding deaths within the first 3 years after baseline did not change these associations. Excluding those with a smoking history, obstructive lung disease, or cancer attenuated the associations of calf circumference (men) and body mass index (women).Conclusions.Based on the stronger association with mortality and given a more easy assessment in older persons, mid-upper arm circumference seems a more feasible and valid anthropometric measure of thinness than body mass index in older men and women. © 2010 The Author. Published by Oxford University Press on behalf of The Gerontological Society of America

Exploring cut-off values for large waist circumference in older adults: a new methodological approach

BACKGROUND: There is an ongoing debate about the applicability of current criteria for large waist circumference (WC) in older adults. OBJECTIVES: Our aim was to explore cut-off values for large WC in adults aged 70 years and older, using previously used and new methods. DESIGN: Prospective cohort study. PARTICIPANTS: Data of 1049 participants of the Longitudinal Aging Study Amsterdam (LASA) (1995-1996), aged 70-88y, were used. MEASUREMENTS: Measured BMI and WC, and self-reported mobility limitations. RESULTS: Linear regression analyses showed that the values of WC corresponding to BMI of 25kg/m2 and 30kg/m2 were higher than the current cut-offs. Cut-offs found in men were 97 and 110cm, whereas 88 and 98cm represented the cut-offs in women. Areas under the Receiver Operating Characteristic (ROC) curves showed that the accuracy to predict mobility limitations improved when the higher cut-offs were applied. Spline regression curves showed that the relationship of WC with mobility limitations was U-shaped in men, while in women, the risk for mobility limitations increased gradually with increasing WC. However, at the level of current cut-off values for WC the odds for mobility limitations were not increased. CONCLUSION: Based on results of extensive analyses, this study suggests that the cut-offs for large WC should be higher when applied to older adults. The association of WC with other negative health outcomes needs to be investigated to establish the final cut-points