Fetal growth is reduced at high altitude, but the decrease is less among long-resident populations. We hypothesized that greater maternal uteroplacental O 2 delivery would explain increased fetal growth in Andean natives versus European migrants to high altitude. O 2 delivery was measured with ultrasound, Doppler and haematological techniques. Participants (n = 180) were pregnant women of self-professed European or Andean ancestry living at 3600 m or 400 m in Bolivia. Ancestry was quantified using ancestry-informative single nucleotide polymorphims. The altitude-associated decrement in birth weight was 418 g in European versus 236 g in Andean women (P < 0.005). Altitude was associated with decreased uterine artery diameter, volumetric blood flow and O 2 delivery regardless of ancestry. But the hypothesis was rejected as O 2 delivery was similar between ancestry groups at their respective altitudes of residence. Instead, Andean neonates were larger and heavier per unit of O 2 delivery, regardless of altitude (P < 0.001). European admixture among Andeans was negatively correlated with birth weight at both altitudes (P < 0.01), but admixture was not related to any of the O 2 transport variables. Genetically mediated differences in maternal O 2 delivery are thus unlikely to explain the Andean advantage in fetal growth. Of the other independent variables, only placental weight and gestational age explained significant variation in birth weight. Thus greater placental efficiency in O 2 and nutrient transport, and/or greater fetal efficiency in substrate utilization may contribute to ancestry-and altitude-related differences in fetal growth. Uterine artery O 2 delivery in these pregnancies was 99 ± 3 ml min −1 , ∼5-fold greater than near-term fetal O 2 consumption. Deficits in maternal O 2 transport in third trimester normal pregnancy are unlikely to be causally associated with variation in fetal growth.

Fetal growth is decreased at high altitude (> 2700 m). We hypothesized that variation in fetal O 2 delivery might account for both the altitude effect and the relative preservation of fetal growth in multigenerational natives to high altitude. Participants were 168 women of European or Andean ancestry living at 3600 m or 400 m. Ancestry was genetically confirmed. Umbilical vein blood flow was measured using ultrasound and Doppler. Cord blood samples permitted calculation of fetal O 2 delivery and consumption. Andean fetuses had greater blood flow and oxygen delivery than Europeans and weighed more at birth, regardless of altitude (+208 g, P < 0.0001). Fetal blood flow was decreased at 3600 m (P < 0.0001); the decrement was similar in both ancestry groups. Altitude-associated decrease in birth weight was greater in Europeans (−417 g) than Andeans (−228 g, P < 0.005). Birth weight at 3600 m was > 200 g lower for Europeans at any given level of blood flow or O 2 delivery. Fetal haemoglobin concentration was increased, P CO 2 decreased, and the fetal P O 2 /S O 2 curve was left-shifted at 3600 m. Fetuses receiving less O 2 extracted more (r 2 = 0.35, P < 0.0001). These adaptations resulted in similar fetal O 2 delivery and consumption across all four groups. Increased umbilical venous O 2 delivery correlated with increased fetal O 2 consumption per kg weight (r 2 = 0.50, P < 0.0001). Blood flow (r 2 = 0.16, P < 0.001) and O 2 delivery (r 2 = 0.17, P < 0.001) correlated with birth weight at 3600 m, but not at 400 m (r 2 = 0.04, and 0.03, respectively). We concluded that the most pronounced difference at high altitude is reduced fetal blood flow, but fetal haematological adaptation and fetal capacity to increase O 2 extraction indicates that deficit in fetal oxygen delivery is unlikely to be causally associated with the altitude-and ancestry-related differences in fetal growth.

Efficient delivery of genetic material into cells is a critical process to translate gene therapy into clinical practice. In this sense, the increased knowledge acquired during past years in the molecular biology and nanotechnology fields has contributed to the development of different kinds of non-viral vector systems as a promising alternative to virus-based gene delivery counterparts. Consequently, the development of non-viral vectors has gained attention, and nowadays, gene delivery mediated by these systems is considered as the cornerstone of modern gene therapy due to relevant advantages such as low toxicity, poor immunogenicity and high packing capacity. However, despite these relevant advantages, non-viral vectors have been poorly translated into clinical success. This review addresses some critical issues that need to be considered for clinical practice application of non-viral vectors in mainstream medicine, such as efficiency, biocompatibility, long-lasting effect, route of administration, design of experimental condition or commercialization process. In addition, potential strategies for overcoming main hurdles are also addressed. Overall, this review aims to raise awareness among the scientific community and help researchers gain knowledge in the design of safe and efficient non-viral gene delivery systems for clinical applications to progress in the gene therapy field.

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We propose a new and complementary approach to image guidance for monitoring medical interventional devices (MID) with human tissue interaction and surgery augmentation by acquiring acoustic emission data from the proximal end of the MID outside the patient to extract dynamical characteristics of the interaction between the distal tip and the tissue touched or penetrated by the MID. We conducted phantom based experiments (n = 955) to show dynamic tool/tissue interaction during tissue needle passage (a) and vessel perforation caused by guide wire artery perforation (b). We use time-varying auto-regressive (TV-AR) modelling to characterize the dynamic changes and time-varying maximal energy pole (TV-MEP) to compute subsequent analysis of MID/tissue interaction characterization patterns. Qualitative and quantitative analysis showed that the TV-AR spectrum and the TV-MEP indicated the time instants of the needle path through different phantom objects (a) and clearly showed a perforation versus other generated artefacts (b). We demonstrated that audio signals acquired from the proximal part of an MID could provide valuable additional information to surgeons during minimally invasive procedures.