STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): An international consortium of randomised placebo-controlled trials

Background: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis.  Methods: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation.  Discussion: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis

Data from: Where to forage when afraid: Does perceived risk impair use of the foodscape?

The availability and quality of forage on the landscape constitute the foodscape within which animals make behavioral decisions to acquire food. Novel changes to the foodscape, such as human disturbance, can alter behavioral decisions that favor avoidance of perceived risk over food acquisition. Although behavioral changes and population declines often coincide with the introduction of human disturbance, the link(s) between behavior and population trajectory are difficult to elucidate. To identify a pathway by which human disturbance may affect ungulate populations, we tested the Behaviorally Mediated Forage-Loss Hypothesis, wherein behavioral avoidance is predicted to reduce use of available forage adjacent to disturbance. We used GPS-collar data collected from migratory mule deer (Odocoileus hemionus) to evaluate habitat selection, movement patterns, and time-budgeting behavior in response to varying levels of forage availability and human disturbance in three different populations exposed to a gradient of energy development. Subsequently, we linked animal behavior with measured use of forage relative to human disturbance, forage availability, and quality. Mule deer avoided human disturbance at both home range and winter range scales, but showed negligible differences in vigilance rates at the site level. Use of the primary winter forage, sagebrush (Artemisia tridentata), increased as production of new annual growth increased but use decreased with proximity to disturbance. Consequently, avoidance of human disturbance prompted loss of otherwise available forage, resulting in indirect habitat loss that was 4.6-times greater than direct habitat loss from roads, well pads, and other infrastructure. The multiplicative effects of indirect habitat loss, as mediated by behavior, impaired use of the foodscape by reducing the amount of available forage for mule deer—a consequence of which may be winter ranges that support fewer animals than they did before development