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David Hawkins

Publications and source records attributed to David Hawkins.

4 recordsLinked to original sources

An investigation of the interactions between lower-limb bone morphology, limb inertial properties and limb dynamics.

Bone mass and size clearly affect the safety and survival of wild animals as well as human beings, however, little is known about the interactions between bone size and movement dynamics. A modeling approach was used to investigate the hypothesis that increased bone cortical area causes increased limb moments of inertia, decreased lower-limb movement maximum velocities, and increased energy requirements to sustain submaximum lower-limb locomotion movements. Custom software and digital data of a human leg were used to simulate femur, tibia, and fibula cortical bone area increases of 0%, 22%, 50%, and 80%. Limb segment masses, center of mass locations, and moments of inertia in the sagittal plane were calculated for each bone condition. Movement simulations of unloaded running and cycling motions were performed. Linear regression analyses were used to determine the magnitude of the effect cortical area has on limb moment of inertia, velocity, and the internal work required to move the limbs at a given velocity. The thigh and shank moment of inertia increased linearly up to 1.5% and 6.9%, respectively for an 80% increase in cortical area resulting in 1.3% and 2.0% decreases in maximum unloaded cycling and running velocities, respectively, and in 3.0% and 2.9% increases in internal work for the cycling and running motions, respectively. These results support the hypothesis and though small changes in movement speed and energy demands were observed, such changes may have played an important role in animal survival as bones evolved and became less robust.

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Safety and efficacy of saquinavir soft-gelatin capsules + zidovudine + optional lamivudine in pregnancy and prevention of vertical HIV transmission.

BACKGROUND: The treatment of HIV infection during pregnancy significantly and substantially reduces the risk of mother-to-child transmission. Although triple therapy is the standard of care for management of HIV infection in adults, the safety of many approved antiretroviral agents in pregnancy is not currently established. METHODOLOGY: An open-label pilot study conducted in Thailand and the UK of the safety of saquinavir soft-gel capsules 1200 mg three times daily administered in the second and third trimester of pregnancy in combination with local standard-of-care antiretroviral therapy. Infants received local standard-of-care antiretroviral therapy after delivery. Steady-state pharmacokinetics were performed in a subset of mothers at 4 weeks after the commencement of saquinavir therapy and paired samples collected from the mother and infant cord blood at delivery. RESULTS: Eighteen antiretroviral-naive pregnant women with a mean viral load of 4.2 log10 and CD4 cell count of 481/mm(3) were recruited. All patients received zidovudine and 3 (all in the UK) received lamivudine. There were no serious adverse events and no discontinuations due to adverse events. Viral load declined by 1.6 log10 at week 4 and was less than 400 copies/mL at delivery in 16/17 mothers. Sixteen live births were recorded, with two in utero deaths-one secondary to an accident and the second due to antiphospholipid syndrome. Both deaths were considered by investigators to be unrelated to study therapy. All infants were HIV negative at subsequent follow-up and no fetal abnormalities were observed. Pharmacokinetic data suggested that mothers had relatively low exposures to saquinavir despite an excellent virologic response. Saquinavir was not detected in cord blood. DISCUSSION: Saquinavir soft-gel capsules are well tolerated during pregnancy and are not associated in this small study with birth abnormalities. Transmission of HIV infection from mother to child was successfully prevented in all cases. Low maternal exposures of saquinavir were noted. However, these did not appear to affect virologic efficacy of the combination. Samples from cord blood indicate minimal fetal exposure to saquinavir.

Adult↗