Activation of myosin light chain kinase (MLCK) and other kinases was studied in the arteries
Apoptosis is a process of programmed cell death. Mammary gland involution is a tissue remodelling process. Mammary epithelial cell apoptosis is an integral component of tissue remodelling but it is only one element. Equally important are the factors which degrade basement membrane and extracellular matrix. Both operations are required for completion of mammary gland involution. The primary apoptotic process occurs first and is temporally distinct from the second stage of involution typified by lobular-alveolar collapse. Local factors related to milk accumulation trigger the first stage, but loss of systemic hormonal stimulation governs the second stage. Changes in the expression patterns of cell cycle control genes and bcl-2 family member genes are found in the first stage. Proteinase gene activation dominates the second stage. These findings support a two stage model of mammary gland involution. Both mammary epithelial cell apoptosis and mammary gland remodelling advance through a process which includes both loss of survival factors and gain of death factors. This review focuses on signalling pathways and genetic controls which are activated and repressed during mammary gland involution.
exchange rate fluctuations, country's attributes modification, and drug price changes. Each price evaluation event implied the calculation of a new drug price and the model generated drug price evolution in each country over time. Model inputs were obtained from a literature review and consultation of representatives of competent authorities and international organizations. The model was validated by assessing actual drug prices at launch and over time for 53 randomly selected medicines. This model was developed for the EU Commission. Results: The model could be used to assess the impact of pricing policies. For example, it showed that the price erosion predicted under the effects of ERP only was for most products slower than observed in reality, and thus that price negotiations also importantly contributed to price erosion. It can also be used to compare alternative launch sequences. The simulated price trends over time were consistent with observed trends. ConClusions: This DES model is the first comprehensive ERP published model across drug life cycle that allows testing various policy scenarios and predict impact of ERP in the real-life. This flexible model may prove useful tool to support decision making from the perspective of authorities or industry. PRM65 Review of Models used in econoMic analyses of new oRal tReatMents foR tyPe 2 diabetes Mellitus
OBJECTIVES:This study was conducted in order to compare the SG with the rating scale (RS) and time trade-off (TTO) techniques in terms of their feasibility, comparability, and reliability in the EQ-5D-5L valuation survey of the general Korean population. METHODS: Five-hundred members of the general Korean population were recruited using a multi-stage quota sampling method in Seoul and its surrounding areas, Korea. Respondents evaluated the 9 EQ-5D-5L health states using a visual analogue scale (VAS), SG and TTO during a personal interview. Feasibility was assessed in terms of the level of difficulty, administration time, and inconsistent responses. Comparability was evaluated using correlation and the Bland-Altman approach. Test-retest reliability was analyzed using the intraclass correlation coefficient (ICC). RESULTS: Of the three methods, VAS was the easiest and quickest method to respond. The SG method did not differ significantly compared to the TTO method in administration time as well as the level of difficulty. The SG and TTO values were highly correlated (rϭ0.992), and the average mean difference between the SG and the TTO values was 0.034. The ICCs of the VAS, SG, and TTO scores were 0.906, 0.841, and 0.827, respectively. CONCLUSIONS: This study suggests that the SG method compared with the VAS and TTO method was feasible and offered a reliable tool for population-based, health state valuation studies in Korea.
morning stiffness), BASFI, ASQoL and the SF-36. Literature review, and clinician and patient interviews, provided information on instrument content validity. Statistical analysis of measurement properties evaluated the reliability (testretest and internal consistency), responsiveness and construct validity. Measurement properties were assessed using data from the RAPID-axSpA trial investigating certolizumab pegol (CZP) efficacy in axSpA. RESULTS: Reviewed AS literature revealed relevant concepts: physical function, pain, disease activity, morning stiffness, fatigue, disturbed sleep, depression, mobility problems, problems performing recreational activities/household tasks/self-care/work, and problems socializing. The same concepts were evident for the overall axSpA population in expert interviews. Concepts identified in patient interviews were consonant with both literature and expert opinion. All PRO instruments were satisfactorily reliable in the RAPID-axSpA population, with all test-retest intraclass correlation coefficients and internal consistency Cronbach's alphas >0.8. Validity was supported by agreement between PRO and clinician-rated measures. All the PRO measures showed good sensitivity to change, with large response sizes (effect size >0.8) on almost all measures from week 12 in RAPID-axSpA. No significant variations in psychometric properties were noted between axSpA sub-populations. CONCLUSIONS: This study indicates that both the content validity and the measurement properties of PRO instruments used in AS are preserved in the broad axSpA population. Questions remain about relying on classical test theory for validation and the value of using generic outcome measures when well-developed disease-specific measures are available.
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