Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever.

BACKGROUND: Although previous studies have revealed the contribution of an initial high level of dengue virus replication to the severe and potentially life-threatening diseases dengue hemorrhagic fever (DHF) and dengue shock syndrome, the involvement of dengue virus in the immunopathological processes during the transition from fever to defervescence, which is a critical stage in determining the progression to DHF, has not been appreciated. Previously, we reported that dengue virus can be detected in the immune complexes of patients with DHF during this period. METHODS: We investigated plasma dengue viral load, virus in immune complexes, antibody response, complements, and cytokines for 54 patients with dengue fever (a relatively mild form of disease) and 49 patients with DHF. The patients had confirmed secondary infection with dengue virus type 2 from a large outbreak in southern Taiwan in 2002. RESULTS: Patients with DHF had a significantly higher viral load and a slower rate of clearance than patients with dengue fever. For viral loads >5.7 log RNA copies/mL on the day of defervescence, the positive and negative predictive values for DHF are 0.88 and 0.95, respectively. A higher level and slower decline of dengue virus-containing immune complexes (and a subsequently higher elevation of C5a and soluble interleukin 2 receptor) were found in patients with DHF, compared with patients with dengue fever. CONCLUSIONS: These findings indicate that slower rates of clearance of viral load and virus-containing immune complexes are associated with subsequent immune activation and contribute to the progression of DHF at this critical stage. Moreover, viral load on the day of defervescence can predict cases of DHF.

PID tuning rules for SOPDT systems: review and some new results.

PID controllers are widely used in industries and so many tuning rules have been proposed over the past 50 years that users are often lost in the jungle of tuning formulas. Moreover, unlike PI control, different control laws and structures of implementation further complicate the use of the PID controller. In this work, five different tuning rules are taken for study to control second-order plus dead time systems with wide ranges of damping coefficients and dead time to time constant ratios (D/tau). Four of them are based on IMC design with different types of approximations on dead time and the other on desired closed-loop specifications (i.e., specified forward transfer function). The method of handling dead time in the IMC type of design is important especially for systems with large D/tau ratios. A systematic approach was followed to evaluate the performance of controllers. The regions of applicability of suitable tuning rules are highlighted and recommendations are also given. It turns out that IMC designed with the Maclaurin series expansion type PID is a better choice for both set point and load changes for systems with D/tau greater than 1. For systems with D/tau less than 1, the desired closed-loop specification approach is favored.