Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.

[Q]: Greenwich is on the River, five miles from the middle of London, and its history is two thousand years old. The first English people were fishermen there, and they named the place Greenwich, meaning "green village". Later the English kings and queens lived at Greenwich in their beautiful places. The name of the earliest palace was Placentia. Henry VIII lived there. He knew that England must be strong at sea. So he started two big ship-yards at Greenwich. But trouble was coming to Greenwich. In 1649, a war started in England and for eleven years there was no king. The men who had worked for him at Placentia decided to live the place themselves. They sold all its beautiful things. Finally, the war ended and King Charles II came back. But Placentia was falling down. So King Charles built a new and bigger palace, which is now open to the public. At this time, Charles was worried about losing so many of its ships at sea: their sailors did not know how to tell exactly where they were. So in 1675, Charles made John Flamsteed, the first astronomer in England, try to find the answer. Flamsteed worked in a new building on the high ground in Greenwich Park. From it with a telescope which he made himself, Flamsteed could look all round the sky. And he did, night after night, for twenty years. Carrying on Flamsteed's work a hundred years later, an astronomer called Harrison finally made a clock which told the time at sea, and helped sailors to know where they were. You can see Harrison's clock, still working, in Greenwich's museum of the sea. Because of Flamsteed's work, every country in the world now tells its time by Greenwich Time.
[A]: Who made the first clock which could tell the time at sea?


[Q]: Spleen tyrosine kinase (Syk) is a cytoplasmic tyrosine kinase involved in signalling in many of the cells that drive immune inflammation. The development of small molecules that inhibit Syk kinase may change the way we treat disorders such as rheumatoid arthritis (RA), as well as a range of other inflammatory diseases. Fostamatinib (R-788) is an orally bioavailable small molecule. It is the prodrug of R406, which is a potent Syk inhibitor. Fostamatinib was developed because it has more favourable physiochemical properties. It is rapidly converted to R406 by intestinal enterocytes. It has been evaluated in experimental models of RA, such as collagen-induced arthritis. In these models, fostamatinib suppressed clinical arthritis, bone erosions, pannus formation and synovitis. A phase II programme with fostamatinib has largely been completed. Three key trials have been published, lasting 12-26 weeks and each enrolling 189-457 patients (875 in total). All these trials involved placebo therapy and patients continued to receive methotrexate in addition to active treatment with fostamatinib. The first dose-ranging trial evaluated three treatment doses in RA patients who had not fully responded to methotrexate therapy. The second trial compared two treatment doses in patients who had not responded to methotrexate therapy. The third trial compared a single treatment dose with placebo in patients who had not responded to biological therapy. The primary outcome measure was the number of patients achieving American College of Rheumatology (ACR) 20% (ACR20) responses. Placebo ACR20 response rates in all three trials were similar (35-38%). All three trials involved one treatment arm receiving fostamatinib 100 mg twice daily; ACR20 responses with this active treatment ranged from 38% to 67%. A meta-analysis of ACR responses in these trials, using responses to the highest dose in each trial for comparisons with placebo therapy in a random effects model, showed a borderline benefit with ACR20 responses. There were more significant differences with ACR50 and ACR70 responses. The reason that this meta-analysis was not more strongly positive is that the third trial, which evaluated patients who had failed to respond to biological treatments, gave negative results. Individual ACR response components, such as changes in swollen joint counts, showed significant differences in the first two trials, but there were no definite treatment benefits in the third trial. Overall, the differences were significant in a meta-analysis of all three trials. The most important adverse reactions were diarrhoea, neutropenia and raised ALT levels, which all showed significant excesses with active treatment compared with placebo. Too few patients have been studied for a definitive safety profile to be known. Overall, the results of the phase II trials were sufficiently encouraging for a phase III programme to be initiated. It will be some years before their definitive results are available.
[A]: Which enzyme is inhibited by a drug fostamatinib?


[Q]: With an ageing population and improving cancer therapies, the two most common benign and malignant bone diseases, osteoporosis and bone metastases, will continue to affect an increasing number of patients. Our expanding knowledge of the molecular processes underlying these conditions has resulted in novel bone targets that are currently being explored in clinical trials. Clearly, the approval of denosumab, a monoclonal antibody directed against RANKL, has just marked the beginning of a new era for bone therapy with several additional new therapies lining up for clinical approval in the coming years. Potential agents targeting the osteoclast include cathepsin K, currently in phase 3 trials, and src inhibitors. Amongst anabolic agents, inhibitors of the Wnt-inhibitor sclerostin and dickkopf-1 are promising in clinical trials. Here, we will provide a comprehensive overview of the most promising agents currently explored for the treatment of bone diseases.
[A]:
To the ligand of which receptors does Denosumab (Prolia) bind?