The Richards model considers only the cumulative infected population size with saturation in growth as the outbreak progresses, which can be caused by other factors such as implementation of control measures. Although data by reporting date is often and typically scrambled by artificial factors such as health system alertness, public response, and government responsiveness, the Richards model is able to capture the turning points of outbreaks because they are often results of these artificial factors. We note, however, that the skewness in an epidemic curve, as quantified by the exponent of deviation "a" in the Richards model which describes the curvature of a given cumulative case data, also could conceivably arise from various other intrinsic factors such as spatial heterogeneity and individual heterogeneity in contact (see [39] , pp. 281 for example) which is not captured by this simple model. This type of modeling, although somewhat simplistic and subsequently limited in its quantification of complex factors, nevertheless enables us to ascertain the impact of these artificial factors through the temporal changes of an outbreak, especially in the events when detailed epidemic data describing disease transmissions and other relevant data (such as that of intervention measures in this case) are not readily available for the construction of a complete disease transmission model and the reliable estimation of model parameters, as in this study Moreover, the use of cumulative numbers could often, or at least partially, smooth out stochastic variations that typically occur in epidemic data, and hence the Richards model could be a valuable tool in providing clues to the challenging task of public health policy evaluation and planning. Molecular mechanisms of inflammation and tissue injury after major trauma-is complement the "bad guy"? Trauma represents the leading cause of death among young people in industrialized countries. Recent clinical and experimental studies have brought increasing evidence for activation of the innate immune system in contributing to the pathogenesis of trauma-induced sequelae and adverse outcome. As the "first line of defense", the complement system represents a potent effector arm of innate immunity, and has been implicated in mediating the early posttraumatic inflammatory response. Despite its generic beneficial functions, including pathogen elimination and immediate response to danger signals, complement activation may exert detrimental effects after trauma, in terms of mounting an "innocent bystander" attack on host tissue. Posttraumatic ischemia/reperfusion injuries represent the classic entity of complement-mediated tissue damage, adding to the "antigenic load" by exacerbation of local and systemic inflammation and release of toxic mediators. These pathophysiological sequelae have been shown to sustain the systemic inflammatory response syndrome after major trauma, and can ultimately contribute to remote organ injury and death. Numerous experimental models have been designed in recent years with the aim of mimicking the inflammatory reaction after trauma and to allow the testing of new pharmacological approaches, including the emergent concept of site-targeted complement inhibition. The present review provides an overview on the current understanding of the cellular and molecular mechanisms of complement activation after major trauma, with an emphasis of emerging therapeutic concepts which may provide the rationale for a "bench-to-bedside" approach in the design of future pharmacological strategies. Despite significant advances in injury prevention, prehospital resuscitation strategies, and modern intensive care, trauma remains the main cause of death in young people in the United States, resulting in more years of potential life lost before the age of 75 years than any other disease [1] [2] [3] [4] . Until present, the pathophysiology of major trauma remains poorly understood [5, 6] . In principle, the pathophysiological sequelae of major injuries are characterized by the initial traumatic impact (so-called "first hit"), followed by a cascade of subsequent immunological reactions, which render the patient susceptible to a potentially detrimental "second hit" insult [7] . The activation of innate immune response mechanisms has been characterized as a crucial event initiating the early phase of hyperinflammation within hours to days after major trauma [6] [7] [8] . While innate immunity is classically considered to be the immediate "first line of defense" against non-self antigens (e.g. infectious pathogens), a traumatic insult can induce a similarly potent acute inflammatory response [9] [10] [11] [12] [13] . The trauma-induced immune response may be limited locally, as in isolated injuries, or result in a massive systemic immune activation, as in patients with multiple injuries [1] . The endogenous triggers of trauma-associated inflammation have been thoroughly investigated and characterized in recent years [7, 14] . The so-called "first hit" induced by a traumatic impact leads to the appearance of an arsenal of "damage-associated molecular patterns" (DAMPs) that are recognized by receptors of immune cells [15] . DAMPs represent a recently characterized large superfamily of danger signals which can activate innate immune responses after trauma or trauma-induced complications, such as infection and sepsis [7, 16] . The DAMP family of danger signals includes the so-called "pathogenassociated molecular patterns" (PAMPs) and molecules termed "alarmins" [17] . The list of molecules belonging to the DAMP family has been increasing dramatically in recent years, and their pathophysiological function in mediating trauma-induced inflammation is far from being fully understood [18] . PAMPs represent a heterogenic entity of recently described inflammatory molecules related to the innate immune system [17, 19] . These microbial molecules are recognized by the immune system as foreign due to their characteristic molecular patterns. In contrast, the so-called "alarmins" represent the correlate of PAMPs for all non-pathogen-derived danger signals which originate from tissue injury [17] . This heterogeneic group of danger molecules is capable of activating innate immune responses in response to tissue damage and cell injury. The alarmins comprise the "heat-shock proteins" (HSPs), annexins, defensins, as well as "classical" markers of tissue injury, such as the S100 protein and the high mobility group box 1 (HMGB1) protein [17, 20] .