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The incident occurred at 11:03 p.m. on Friday in the parking lot of a Fiesta store in Cullen Plaza near Wilmington.
Commander K. Anthony Miller with HPD said a suspect, described as a white man, began arguing with another person in a wheelchair before another man tried intervening.
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That is when the suspect allegedly fired a weapon towards the man, and killed him, according to police.
Police said the suspect was not wearing a shirt and fled southbound on foot.
There is an active investigation going on at this time, officials said.