Challenges and recent progress in drug discovery for tropical diseases

Infectious tropical diseases have a huge effect in terms of mortality and morbidity, and impose a heavy economic burden on affected countries. These diseases predominantly affect the world’s poorest people. Currently available drugs are inadequate for the majority of these diseases, and there is an urgent need for new treatments. This Review discusses some of the challenges involved in developing new drugs to treat these diseases and highlights recent progress. While there have been notable successes, there is still a long way to go.</p

The effects of endogenous and exogenous androgens on cardiovascular disease risk factors and progression

Cardiovascular disease incidence rates have long been known to significantly differ between the two sexes. Estrogens alone fail to explain this phenomenon, bringing an increasing amount of attention to the role of androgens. Contrary to what was initially hypothesized, androgens seem to have an overall cardioprotective effect, especially in men. Recent studies and published data continue to support this notion displaying a consistent inverse correlation with atherosclerosis progression and cardiovascular disease both in regressive and prospective study models. Clinical studies have also revealed what seems to be a differential androgenic effect on various cardiovascular risk factors between men and women. Further insight indicates that in order to avoid confusion it may be also preferable to separately examine the effects of endogenous androgen levels from exogenous testosterone administration, as well as discern the differential results of low to normal and supraphysiological administration doses. This review summarizes old and recent data according to the above distinctions, in an attempt to further our understanding of the role of androgens in cardiovascular disease

Sharing a Polluted River Network

A polluted river network is populated with agents (e.g., firms, villages, municipalities, or countries) located upstream and downstream. This river network must be cleaned, the costs of which must be shared among the agents. We model this problem as a cost sharing problem on a tree network. Based on the two theories in international disputes, namely the Absolute Territorial Sovereignty (ATS) and the Unlimitted Territorial Integrity (UTI), we propose three different cost sharing methods for the problem. They are the Local Responsibility Sharing (LRS), the Upstream Equal Sharing (UES), and the Downstream Equal Sharing (DES), respectively. The LRS and the UES generalize Ni and Wang ("Sharing a polluted river", Games Econ. Behav., 60 (2007), 176-186) but the DES is new. The DES is based on a new interpretation of the UTI. We provide axiomatic characterizations for the three methods. We also show that they coincide with the Shapley values of the three different games that can be defined for the problem. Moreover, we show that they are in the cores of the three games, respectively. Our methods can shed light on pollution abatement of a river network with multiple sovereignties

Does the Type, Number or Combinations of Traditional Cardiovascular Risk Factors Affect Early Outcome After Carotid Endarterectomy?

AbstractPurposeThe present study was undertaken in order to assess the 30-day complication rate of carotid endarterectomy (CEA) in relation to the patients' cardiovascular risk factors.MethodsCardiovascular risk factors, operative details, morbidity and mortality of 1002 carotid endarterectomies in 852 patients were prospectively recorded in a database. The indications for surgery were asymptomatic ≥75% or symptomatic ≥50% internal carotid stenosis when other causes of stroke were excluded. Exclusion criteria were intervention for post-CEA restenosis, post-irradiation lesions, kinking of the internal carotid artery, external carotid artery stenosis, endovascular and simultaneous cardiac procedures.ResultsThe 30-day combined minor and major stroke and death rate was 2.7% (27/1002). Significant risk factors in logistic regression model were diabetes (stroke and death rate=5.7%, p=0.002, OR=3.31), the simultaneous presence of three cardiovascular risk factors (stroke and death rate=5.3%, p=0.012, OR=3.11) and the combination diabetes, hypertension and hyperlipidemia (stroke and death rate=9.4%, p=0.001, OR=4.22).ConclusionsTraditional cardiovascular risk factors significantly affect the 30-day stroke and death rate after carotid endarterectomy