g. invasive species, fluctuating lake levels)? Under the uncertainty of future generations’ preferences and needs, what ecological attributes do we need to preserve? Finally, which ecosystem services are most preferred or valued by humans in this

region and therefore should be heavily managed for sustainability? This review helps to identify critical system components and their trends in order to set the stage for further research and to develop models of coupled human and natural systems, which are of vital importance to help protect and sustain aquatic ecosystems. This work was supported in part by the National Science Foundation under award no. EAR-1039122. Thanks to Macomb County Health Department for providing the historical beach monitoring FRAX597 data and to J. Stevenson for reviewing an earlier draft of this paper. We also appreciate LDN-193189 cell line the useful comments from three anonymous reviewers and from the associate editor. We

appreciate the conversations about Lake St. Clair with J. Duris, S. Gasteyer, K. Goodwin, B. Manny, T. Nalepa, P. Seelbach and M. Thomas. “
“Approximately 130–170 million people are chronically infected with HCV, leading to 54,000 deaths and 955,000 disability-adjusted life-years associated with acute HCV infection (Mohd Hanafiah et al., 2013). Chronic hepatitis C can lead to a large spectrum of diseases, including steatosis, fibrosis, cirrhosis, and hepatocellular carcinoma (Perz and Alter, 2006). To date, no protective vaccine is available for HCV infection; over the last decade, therapy has consisted of a 24–48-week course of peginterferon-alpha-2a (PEG-IFN-alpha-2a) or peginterferon-alpha-2b (PEG-IFN-alpha-2b) in combination with the guanosine analogue, ribavirin (RBV). The therapy leads to sustained virologic response (SVR) in 42–52%, 65–85%, and 76–82% of individuals infected with HCV genotype 1; 4, 5, or 6; and 2 or 3, respectively (Antaki et al., 2010 and Hoofnagle and Seeff, 2006). The recently approved non-structural protein (NS) 3/4A protease

inhibitors (PIs) boceprevir (approved by the FDA on May 13, 2011) and telaprevir (approved by the FDA on May 23, 2011), used in combination with PEG-IFN-alpha and RBV for HCV CYTH4 genotype 1 infections, have increased cure rates to approximately 70% (Bacon et al., 2011, Jacobson et al., 2011 and Poordad et al., 2011). However, these triple-therapy regimens may result in unfavourable side effects and emergence of drug-resistant HCV (Bacon et al., 2011, Jacobson et al., 2011 and Poordad et al., 2011), which may reduce virus susceptibility and applicability of current HCV triple therapies (Ozeki et al., 2011). Recently, two more effective compounds have been approved for HCV treatment: the protease inhibitor simeprevir (approved by the FDA in November, 2013) and the nucleotide polymerase inhibitor sofosbuvir (approved by the FDA on December 6, 2013).