Effectiveness of a peer-led self-management program for older people with type 2 diabetes in China

Type 2 diabetes is a common chronic disease, which has a negative health impact and results in enormous economic burden. The prevalence of type 2 diabetes is increasing dramatically and it affects older people disproportionately. The healthcare system in China is faced with an overwhelming burden due to a large ageing population, high prevalence of diabetes and limited healthcare resources. Self-management has been widely accepted as the cornerstone of the clinical management of type 2 diabetes. Since self-management usually involves complex behaviour change and can be emotionally challenging, effective education is essential to facilitate this transition. However, there has been no existing program of type 2 diabetes self-management for older patients in China until now. Furthermore, the generalisation of any health education programs is often hampered due to limited healthcare resources in China. The primary purpose of this study was to develop a socially and culturally suitable self-management program, which addressed self-efficacy and social support to facilitate behaviour change and subsequent health improvement, for older people with type 2 diabetes living in the community in China. The secondary purpose was to test a feasible delivery model of the program through involvement of peer leaders and existing community networks. This study was conducted in three phases. Phase one gathered information about barriers related to self-management behaviours and help needed to address them, from the perspective of older people with type 2 diabetes and community health professionals, through focus group discussion. Data from Phase One, together with guidelines of the selected theoretical frame work, results from an extensive literature review, and experiences of previous relevant studies provided the basis for development of a peer-led type 2 diabetes self-management program (Phase Two). Phase Three involved a pre-test, post-test non-equivalent control group design to test the effectiveness of the self-management program on older people with type 2 diabetes in the community. The impact of the program on peer leaders was examined using a one group pre-test, post-test design. In addition, evaluation of the program from peer leaders’ and older people’s perceptions was conducted through a post-test questionnaire. Older people with type 2 diabetes and health professionals expressed broadly the same concerns, which were: social support; confidence to practice self-management behaviours; self-management behaviours; barriers to self-management behaviours; and advice for ongoing health education. However, their points of view were not always identical and different emphases were identified. The peer-led program produced significant improvement in social support, self-efficacy, self-management behaviours and depressive status in the experimental group, as compared to the non-equivalent control group. However, there was no significant effect on quality of life nor health care utilisation. Therefore, the effectiveness of the program among older people with type 2 diabetes was partially confirmed. In addition, the participants were supportive, giving positive feedback about the program. Suggestions for future improvement were provided as well. After receiving specific peer leader training and assisting in most of the delivery process of the program, the peer leaders improved, significantly, in overall self-management behaviours and in specific areas of social support and self-efficacy, though they did not improve in depressive status, quality of life and health care utlisation. In addition, these peer leaders enjoyed being peer leaders, and gave very positive feedback about the whole program. In conclusion, this study has implications for understanding and facilitating self-management behaviours for older people with type 2 diabetes in China. The peer-led self-management program was effective in improving levels of self-efficacy, social support, self-management behaviours and depressive status among older people with type 2 diabetes living in the community in China. The delivery process involving peer leaders was deemed feasible to implement within the health care system in China. The program is suitable to be used by community health professionals in their practice in China. The study also has potential wider benefit to nursing practice and global health practice

Quantile regression in partially linear varying coefficient models

Semiparametric models are often considered for analyzing longitudinal data for a good balance between flexibility and parsimony. In this paper, we study a class of marginal partially linear quantile models with possibly varying coefficients. The functional coefficients are estimated by basis function approximations. The estimation procedure is easy to implement, and it requires no specification of the error distributions. The asymptotic properties of the proposed estimators are established for the varying coefficients as well as for the constant coefficients. We develop rank score tests for hypotheses on the coefficients, including the hypotheses on the constancy of a subset of the varying coefficients. Hypothesis testing of this type is theoretically challenging, as the dimensions of the parameter spaces under both the null and the alternative hypotheses are growing with the sample size. We assess the finite sample performance of the proposed method by Monte Carlo simulation studies, and demonstrate its value by the analysis of an AIDS data set, where the modeling of quantiles provides more comprehensive information than the usual least squares approach.Comment: Published in at http://dx.doi.org/10.1214/09-AOS695 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

Exploring free-energy landscapes and microscopic interactions of selected small-molecules and proteins wih cell membranes

The present Thesis is devoted to the study of the physical-chemical properties of selected small-molecules (such as amino-acids like tryptophan or hormones like melatonin) and proteins (such as KRAS-4B) absorbed in model lipid bilayers located at physiological environments. Since in such conditions biological membranes composed of phospholipids and cholesterol are surrounded by electrolyte solutions, understanding the interactions of the small molecule or protein with the surrounding phospholipids, cholesterol, water and all sorts of ion species is a topic of great fundamental importance. In particular, the present Thesis has advanced into the analysis of the structural and energetic aspects of an oncogenic protein from the RAS family, characterising the physical conditions that allow such protein to remain anchored to the cell. The findings reported in the Thesis may help to shed light in the understanding of a wide variety of cancers, with direct impact on the design of drugs or treatments useful for curation. The lipids considered in this Thesis include the saturated lipids dimyristoilphosphatidylcholine (DMPC) and dipalmytoilphosphatidylcholine (DPPC), the unsaturated lipids dioleoylphosphatidylcholine (DOPC) and dioleoylphosphatidylserine(DOPS) and cholesterol. Classical molecular dynamics simulations and well-tempered metadynamics simulations have been applied in this thesis so that all considered systems have been modelled and simulated at the all-atom level, with systems containing up to 200000 atoms. Using classical molecular dynamics simulations at the microsecond time scale, we studied the microscopic structure and dynamics of the small-molecules and KRAS4B proteins, the latter in the wild-type and mutated (oncogenic) forms. The cell membrane has been always considered in the liquid crystalline phase, what in some cases required to rise the temperature of the system up to 323 K. Structural properties such as the area per lipid and thickness of the membrane, density profiles, deuterium-order parameters, orientational distributions and the extent of water penetration in the membrane have been analysed. Molecular self-diffusion and spectral densities of atomic species reveal a variety of time scales playing a role in membrane dynamics. The physical meaning of all spectral features from lipid atomic sites is analysed and correlated with experimental data. Most relevant have been the location of individual sites of binding of probes at the interface of the membrane. Finally, using reversible work techniques, we estimated the extent of free energy required to form such liaisons. By applying 1-microsecond well-tempered metadynamics simulations, we have performed systematic free energy calculations of probe binding to the membrane and water for the first time. Free energy landscapes unveil specific binding behaviour of small-molecules and proteins at phospholipid membranes. This Thesis provides a general methodology to explore such free energy landscapes at complex biological interfaces which can be extended to study other interactions of interest between molecules, peptides, proteins or drugs and charged head-groups in colloidal chemistry and biology. We further applied this methodology to study the case of a prototypical oncogenic protein (KRAS), being able to produce a wide variety of cancers. Our results from resulting free energy landscapes indicate the existence of specific hydrogen-bonding connections between parts of the protein (hypervariable region and farnesylated tail) that might be responsible of the permanent infection of healthy cells through its anchoring at the interface of the membrane.La presente Tesis doctoral está dedicada al estudio de las propiedades físico-químicas de moléculas pequeñas seleccionadas (por ejemplo aminoácidos como el triptófano u hormonas como la melatonina) y proteínas (como la KRas-4B) absorbidas en membranas celulares formadas por fosfolípidos y ubicadas en entornos fisiológicos. Dado que en estas condiciones, las membranas biológicas compuestas por fosfolípidos y colesterol están rodeadas de soluciones de electrólitos, entender las interacciones de la molécula pequeña o proteína con los fosfolípidos circundantes, el colesterol, el agua y todo tipo de especies iónicas es un tema de gran importancia fundamental. En particular, la presente Tesis se ha avanzado en el análisis de los aspectos estructurales y energéticos de una proteína oncogènica de la familia Ras, caracterizando las condiciones físicas que permiten que esta proteína se mantenga anclada a la célula. Las resultados descritos a la tesis pueden ayudar a dar luz a la comprensión de una gran variedad de cánceres, con un impacto directo en el diseño de medicamentos o tratamientos útiles para su curación. Los lípidos considerados en esta Tesis incluyen los lípidossaturados dimiristoilfosfatidilcolina y dipalmitoilfosfatidilcolina, los lípidos insaturados dioleoilfosfatidilcolina y dioleoilfosfatidilserina y el colesterol. En esta Tesis se han aplicado simulaciones de dinámica molecular clásica y simulaciones de metadinámica bien temperada, de forma que todos los sistemas considerados han estado modelizados y simulados a nivel puramente atómico, con sistemas de hasta 200000 átomos. Utilizando simulaciones clásicas de dinámica molecular (a escala 1 microsegundo), hemos estudiado la estructura y la dinámica microscópicas de las moléculas pequeñas y las proteínas KRas4B, estas últimas en formas pura y mutada (oncogénica). La membrana celular siempre se ha considerado en fase cristalina líquida, cosa que en algunos casos ha requerido aumentar la temperatura del sistema hasta 323 K. Se han calculado propiedades estructurales como por ejemplo el área por lípido y el grosor de la membrana, perfiles de densidad, parámetros de orden del deuterio, distribuciones orientacionals y el alcance de la penetración del agua a la membrana. Los coeficientes de difusión moleculares y las densidades espectrales atómicas revelan una gran variedad de escalas de tiempos que tienen un papel en la dinámica de membrana. El significado físico de todas las características espectrales de los lugares atómicos lipídicos se ha analizado y correlacionado con datos experimentales. El más relevante ha sido el hallazgo de la ubicación de lugares individuales de enlace de las varias sondas (pequeñas moléculas y proteínas) a la interfaz de la membrana. Finalmente, utilizando técnicas de trabajo reversible, se ha podido estimar la cantidad de energía libre necesaria para formar estos enlaces. Mediante la aplicación de simulaciones de metadinámica bien temperada de 1 microsegundo, hemos realizado por primera vez cálculos de energía libre sistemática de la unión de las varias sondas a la membrana y al agua. Las superficies de energía libre muestran un comportamiento específico de los enlaces de moléculas pequeñas y proteínas a las membranas fosfolípidiques. Esta Tesis proporciona una metodología general para explorar superficies de energía libre en interfaces biológicas complejas que se pueden ampliar para estudiar otras interacciones de interés entre moléculas, péptidos, proteínas o fármacos y membranas en Química y Biología coloidal. También hemos aplicado esta metodología para estudiar el caso de una proteína oncogènica prototípica (KRas), que se considera responsable de una gran variedad de cánceres. Nuestros resultados en superficies de energía libre indican la existencia de conexiones específicas de enlace de hidrógeno entre partes de la proteína (región hipervariabley cola farnesilada) que podrían ser responsables de la infección permanente de células sanas a través de su anclaje a la interfaz de la membrana.Postprint (published version

Inverse Synthetic Aperture Radar Imaging for Micro-motion Target with Rotating Parts

This paper establishes imaging model for rigid body micro-motion target with rotating parts, and derives the formulas of micro-Doppler induced by target with rotation. To obtain well-focused inverse synthetic aperture radar image of rigid body micro-motion target with rotating parts, low frequency filter algorithm is presented to separate the echoes of the rigid body from that of the micro-motion parts. The results of measured data confirm the effectiveness of the proposed method.Defence Science Journal, 2013, 63(5), pp.521-523, DOI:http://dx.doi.org/10.14429/dsj.63.408

Crop improvement through genetic engineering: development of transformation technologies and production of stress tolerant transgenic crops

With the increase of environmental degradation, the crop improvement of stress tolerance becomes more important. Little success, however, has been achieved through traditional breeding method because of the limited availability of germplasm and the complexity of the genetic control of stress tolerance traits. Genetic engineering allows gene transfer between unrelated species. It greatly widens the genetic resource and is a good alternative for the improvement of stress tolerance. The goal of this study is to produce stress-tolerant maize and soybean to adapt to environmental stresses. Genetic transformation is used as a tool to achieve the goal. Since transformation technologies in maize and soybean are not robust in the respects of transformation efficiency and the quality of resulted products, the study also was focused on the development and optimization of maize and soybean transformation technologies.;Two available soybean transformation protocols were explored. Factors affecting the transformation efficiency of Agrobacterium-mediated cotyledonary node protocol were studied and optimized. Efforts also were made to repeat the controversial transformation protocol-soybean pollen-tube pathway transformation protocol because of the great interest with the tissue-culture free feature of the protocol. The result indicated that soybean pollen-tube pathway transformation is not reproducible. This study established a new Agrobacterium-mediated maize transformation protocol using a standard binary vector system. The resulting transgenic maize plants then were evaluated. Results showed that transformants generated from this new method have better qualities compared with those obtained from particle bombardment transformation.;This study showed that the expression of a tobacco mitogen-activated protein kinase kinase kinase gene, Nicotiana protein kinase 1 (NPK1) gene improved the freezing and drought tolerance in maize. This is the first report that freezing and drought traits were achieved in major crop maize through genetic engineering approach. Transgenic maize was identified to have elevated levels of several stress related gene expression, including DREB1, EREBP, EREBR1, GST and small HSP, indicating that the active NPK1 has induced the oxidative signaling pathway as expected and, therefore, protected maize plants from stress damage. NPK1 transgenic soybean also was produced. However, no advantage in drought tolerance was detected in these transgenic soybeans