Conditional conservatism and debt versus equity financing

SMU SOA

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Treatment of cryptosporidiosis in immunocompromised individuals: systematic review and meta-analysis

Cryptosporidium is a common cause of gastroenteritis and is associated with severe life-threatening illness among immunocompromised individuals. This review aimed to assess the efficacy of interventions for the treatment and prevention of cryptosporidiosis among immunocompromised patients. A search of Medline, Embase and other electronic databases was carried out up to August 2005. Two reviewers independently extracted data and assessed study quality. The relative risk for each intervention was calculated. Seven trials involving 169 participants were included. Nitazoxanide and paramomycin were associated with a relative risk (RR) of reduction in the duration and frequency of diarrhoea of 0.83 [95% confidence interval (CI) 0.36, 1.94] and 0.74 (95% CI 0.42, 1.31), respectively, showing no evidence of effectiveness. Nitazoxanide led to significant evidence of oocyst clearance compared with placebo with a RR of 0.52 (95% CI 0.30, 0.91). The effect was not significant for HIV-seropositive participants (RR 0.71, 95% CI 0.36, 1.37). HIV-seronegative participants on nitazoxanide had a significantly higher relative risk of achieving parasitological clearance of 0.26 (95% CI 0.09, 0.80) based on a single study. No other intervention was associated with either a reduction in diarrhoea, mortality or a significant parasitological response. This review confirms the absence of evidence for effective agents in the management of cryptosporidiosis. The results indicate that nitaxozanide reduces load of parasites and may be useful in immunocompetent individuals. The absence of effective therapy highlights the importance of preventive interventions in this group of patients