TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: Aggrecanase cleavage at the 392Glu-393Ala bond in the interglobular domain (IGD) of aggrecan, releasing N-terminal 393ARGS fragments, is an early key event in arthritis and joint injuries. Here, we use a quantitative immunoassay of aggrecan ARGS neoepitope fragments in human synovial fluid to determine if this cleavage-site specific method better identifies joint pathology than previously available less specific aggrecan assays.', 'Synovial fluid (SF) from 26 people with healthy knees (reference) and 269 patients were analyzed in a cross-sectional study. Patient groups were acute inflammatory arthritis, acute knee injury, chronic knee injury and knee osteoarthritis (OA). Aggrecan ARGS fragments were assayed by ELISA using the monoclonal antibody OA-1. Total aggrecan content was analyzed by an ELISA using the monoclonal antibody 1-F21, and sulfated glycosaminoglycan by Alcian blue precipitation.', 'Aggrecan ARGS fragment concentrations in all groups differed from the reference group (P < 0.001). The acute inflammatory arthritis group had the highest median level, 177-fold greater than that of the reference group. Median levels (in pmol ARGS/ml SF) were: reference 0.5, acute inflammatory arthritis 88.5, acute knee injury 53.9, chronic knee injury 0.5 and OA 4.6. In contrast, aggrecan and sulfated glycosaminoglycan concentrations varied much less between groups, and only acute inflammatory arthritis and acute knee injury were found to have a two-fold increase in median levels compared to the reference.
Answer: Levels of aggrecan ARGS fragments in human synovial fluid are increased in human arthritis, OA and after knee injury, likely reflecting an enhanced cleavage at the 392Glu-393Ala bond in the IGD by aggrecanase. An assay that specifically quantified these fragments better distinguished samples from joints with pathology than assays monitoring aggrecan or glycosaminoglycan concentrations. The newly developed ARGS fragment assay can be used to monitor aggrecanase activity in human joint disease and experimental models.

SOLUTION: Is synovial fluid level of aggrecan ARGS fragments a more sensitive marker of joint disease than glycosaminoglycan or aggrecan levels : a cross-sectional study?

PROBLEM: Context: A computerized physician order entry (CPOE) system with embedded clinical decision support can reduce medication errors in hospitals, but might increase the time taken to generate orders.', 'We aimed to quantify the effects of temporal (month, day of week, hour of shift) and other factors (grade of doctor, prior experience with the system, alert characteristics, and shift type) on the time taken to generate a prescription order.', 'A large university teaching hospital using a locally developed CPOE system with an extensive audit database.', 'We retrospectively analyzed prescription orders from the audit database between August 2011 and July 2012.', 'The geometric mean time taken to generate a prescription order within the CPOE system was 11.75\u2005s (95% CI 11.72 to 11.78). Time to prescribe was most affected by the display of high-level (24.59\u2005s (24.43 to 24.76); p<0.001) or previously unseen (18.87\u2005s (18.78 to 18.96); p<0.001) alerts. Prescribers took significantly less time at weekends (11.29\u2005s (11.23 to 11.35)) than on weekdays (11.88\u2005s (11.84 to 11.91); p<0.001), in the first (11.25\u2005s (11.16 to 11.34); p<0.001) and final (11.56\u2005s (11.47 to 11.66); p<0.001) hour of their shifts, and after the first month of using the system.
Answer: The display of alerts, prescribing experience, system familiarity, and environment all affect the time taken to generate a prescription order. Our study reinforces the need for appropriate alerts to be presented to individuals at an appropriate place in the workflow, in order to improve prescribing efficiency.

SOLUTION: Do temporal and other factors that influence the time doctors take to prescribe using an electronic prescribing system?

PROBLEM: Context: This study investigated whether off-pump coronary bypass graft operations on the beating heart under normothermic conditions reduces the systemic oxidative stress and inflammatory reaction seen in patients operated under cardiopulmonary bypass (CPB).', 'A cardiac stabilizer (Octopus Tissue Stabilizer; Medtronic Inc, Minneapolis, MN) was used to perform the coronary anastomoses on the normothermic beating heart with or without CPB. Serial blood samples were taken at various intervals. Plasma was analyzed for several oxidative stress and inflammatory markers.', 'Significant increases from prior anesthesia values of lipid hydroperoxides (190% at 4 hours), protein carbonyls (250% at 0.5 hours) and nitrotyrosine (510% at 0.5 hours) were seen in the CPB group, but they were abolished or significantly reduced in the off-pump group. Complement C3a and elastase levels were rapidly increased upon the institution of CPB, and this was followed by increases in IL-8, TNF-alpha, and sE-selectin. In contrast, the rise of these factors was blunted in patients operated without CPB.
Answer: Off-pump coronary bypass graft operation on a beating heart significantly reduces oxidative stress and suppresses the inflammatory reaction associated with the use of CPB.

SOLUTION:
Does off-pump bypass graft operation significantly reduce oxidative stress and inflammation?