The World Trade Center Health Program (WTCHP) General Responder Cohort (the cohort) consists of workers and volunteers who were part of the rescue and recovery effort that followed the 11 September 2001 attack on the World Trade Center towers. Fire Department of New York (FDNY) and Pentagon and Shanksville responders are not included in this cohort but are covered by other similar programmes. This self-selected, open, de facto cohort began to form within a month of 9/11when the rescue and recovery workers began presenting with a variety of respiratory complaints at Mount Sinai's Irving J. Selikoff Center for Occupational and Environmental Medicine. 1-4 In 2002, the National Institute for Occupational Safety and Health (NIOSH) provided funds to provide a one-time medical evaluation, and support for physical and mental health treatment came from philanthropic sources. NIOSH also provided funding, in 2004, for additional medical evaluations and, in 2006, for treatment of both physical and mental health conditions. With the passing of the James Zadroga 9/11 Health and Compensation Act of 2010, 5 more years of medical monitoring and treatment were provided. Who is in the cohort? Estimates of how many rescue and recovery workers and volunteers worked on the WTC effort vary and may never be known, but the City of New York estimate is 91 000. 5,6 As of 31 March 2014, the WTCHP had information on 48 389 potential enrollees (Figure 1), 34 225 of whom were eligible because of their participation in earlier programmes and 3056 more of whom were subsequently deemed eligible. Eligibility criteria are: (i) the person worked or volunteered on the WTC effort for either 4 h

The metabolic and ventilatory responses to steady state submaximal exercise on the cycle ergometer were compared at four intensities in 8 healthy subjects. The trials were performed so that, after a 10 min adaptation period, power output was adjusted to maintain steady state VO2 for 30 min at values equivalent to: (1) the aerobic threshold (AeT); (2) between the aerobic and the anaerobic threshold (AeTAnT); (3) the anaerobic threshold (AnT); and (4) between the anaerobic threshold and VO2max (AnTmax). Blood lactate concentration and ventilatory equivalents for O2 and CO2 demonstrated steady state values during the last 20 min of exercise at the AeT, AeAnT and AnT intensities, but increased progressively until fatigue in the AnTmax trial (mean time = 16 min). Serum glycerol levels were significantly higher at 40 min of exercise on the AeAnT and the AnT when compared to AeT, while the respiratory exchange ratios were not significantly different from each other. Thus, metabolic and ventilatory steady state can be maintained during prolonged exercise at intensities up to and including the AnT, and fat continues to be a major fuel source when exercise intensities are increased from the AeT to the AnT in steady state conditions. The blood lactate response to exercise suggests that, for the organism as a whole, anaerobic glycolysis plays a minor role in the energy release system at exercise intensities upt to and including the AnT during steady state conditions.

The presence of three cohorts strengthens the effort of identifying and quantifying the cancer risk; the heterogeneity in design might increase sensitivity to the identification of cancers potentially associated with exposure. The presence and magnitude of an increased cancer risk remains to be fully elucidated. Continued long-term follow up with minimal longitudinal dropout is crucial to achieve this goal.

This is the first part of a two-article series which will introduce the theory and practice of a proposed set of quantitative methods for benefit-risk analysis. Adjustments to number-needed-to-treat (NNT) analysis and a new method, minimum clinical efficacy (MCE) analysis are presented and critically discussed. The goal of these methods is to condense into a summary metric the benefit-risk profile of a product so that manufacturers, regulators, clinicians and patients can better understand and participate in risk management. A second article will present examples of these methods.