Transthoracic echocardiographic imaging of coronary arteries: tips, traps, and pitfalls

The aim of this paper is to highlight coronary investigation by transthoracic Doppler evaluation. This application has recently been introduced into clinical practice and has received enthusiastic feedback in terms of coronary flow reserve evaluation on left anterior coronary artery disease diagnosis. Such diagnosis represents the most important clinical application but has in itself some limitations regarding anatomical and technological knowledge. The purpose of this paper is to offer a didactic approach on how to investigate the different segments of left anterior and posterior descending coronary arteries by transthoracic ultrasound using different anatomical key structures .as marker

Coronary flow reserve in stress-echo lab. From pathophysiologic toy to diagnostic tool

The assessment of coronary flow reserve by transthoracic echocardiography has recently been introduced into clinical practice with gratifying results for the diagnosis of left anterior descending artery disease simultaneously reported by several independent laboratories. This technological novelty is changing the practice of stress echo for 3 main reasons. First, adding coronary flow reserve to regional wall motion allows us to have – in the same sitting – high specificity (regional wall motion) and a high sensitivity (coronary flow reserve) diagnostic marker, with an obvious improvement in overall diagnostic accuracy. Second, the technicalities of coronary flow reserve shift the balance of stress choice in favour of vasodilators, which are a more robust hyperemic stress and are substantially easier to perform with dual imaging than dobutamine or exercise. Third, the coronary flow reserve adds a quantitative support to the exquisitely qualitative assessment of wall motion analysis, thereby facilitating the communication of stress echo results to the cardiological world outside the echo lab. The next challenges involve the need to expand the exploration of coronary flow reserve to the right and circumflex coronary artery and to prove the additional prognostic value – if any – of coronary flow reserve over regional wall motion analysis, which remains the cornerstone of clinically-driven diagnosis in the stress echo lab

Least weight and least cost optimisation of a passenger vessel

In the scantling design of a passenger ship, minimum production costminimum weight and maximum moment of inertia (stiffness) are conflicting objectives. For that purpose, recent improvements have been made to the LBR-5 software (French acronym of Stiffened Panels Software”, version 5.0) to optimize the scantling of ship sections by considering production cost, weight and moment of inertia in the optimisation objective function. A real multi-criterion optimisation of a passenger ship is presented in this paper. Results highlight that LBR-5 is competitive software to optimise scantling of ships at very early design stage with management of critical problems studied normally at a later step of the design

Multi-criterion scantling optimisation of cruise ships

A numerical tool for the optimisation of the scantlings of a ship is extended by considering production cost, weight and moment of iner tia in the objective function. A multi-criteria optimisation of a passenger ship is conducted to illustrate the analysis process. Pareto frontiers are obtained and results are verified with Bureau Veritas rules

A prospective longitudinal study of perceived infant outcomes at 18-24 months: Neural and psychological correlates of parental thoughts and actions assessed during the first month postpartum

The first postpartum months constitute a critical period for parents to establish an emotional bond with their infants. Neural responses to infant-related stimuli have been associated with parental sensitivity. However, the associations among these neural responses, parenting, and later infant outcomes for mothers and fathers are unknown. In the current longitudinal study, we investigated the relationships between parental thoughts/actions and neural activation in mothers and fathers in the neonatal period with infant outcomes at the toddler stage. At the first month postpartum, mothers (n=21) and fathers (n=19) underwent a neuroimaging session during which they listened to their own and unfamiliar baby’s cry. Parenting-related thoughts/behaviors were assessed by interview twice at the first month and 3-4 months postpartum and infants’ socioemotional outcomes were reported by mothers and fathers at 18-24 months postpartum. In mothers, higher levels of anxious thoughts/actions about parenting at the first month postpartum, but not at 3-4 months postpartum, were associated with infant’s low socioemotional competencies at 18-24 months. Anxious thoughts/actions were also associated with heightened responses in the motor cortex and reduced responses in the substantia nigra to own infant cry sounds. On the other hand, in fathers, higher levels of positive perception of being a parent at the first month postpartum, but not at 3-4 months postpartum, were associated with higher infant socioemotional competencies at 18-24 months. Positive thoughts were associated with heightened responses in the auditory cortex and caudate to own infant cry sounds. The current study provides evidence that parental thoughts are related to concurrent neural responses to their infants at the first month postpartum as well as their infant’s future socioemotional outcome at 18-24 months. Parent differences suggest that anxious thoughts in mothers and positive thoughts in fathers may be the targets for parenting-focused interventions very early postpartum

Antisense-based therapy for the treatment of spinal muscular atrophy

One of the greatest thrills a biomedical researcher may experience is seeing the product of many years of dedicated effort finally make its way to the patient. As a team, we have worked for the past eight years to discover a drug that could treat a devastating childhood neuromuscular disease, spinal muscular atrophy (SMA). Here, we describe the journey that has led to a promising drug based on the biology underlying the disease

Comparison of the Efficacy of MOE and PMO Modifications of Systemic Antisense Oligonucleotides in a Severe SMA Mouse Model

Spinal muscular atrophy (SMA) is a motor neuron disease. Nusinersen, a splice-switching antisense oligonucleotide (ASO), was the first approved drug to treat SMA. Based on prior preclinical studies, both 2'-O-methoxyethyl (MOE) with a phosphorothioate backbone and morpholino with a phosphorodiamidate backbone-with the same or extended target sequence as nusinersen-displayed efficient rescue of SMA mouse models. Here, we compared the therapeutic efficacy of these two modification chemistries in rescue of a severe mouse model using ASO10-29-a 2-nt longer version of nusinersen-via subcutaneous injection. Although both chemistries efficiently corrected SMN2 splicing in various tissues, restored motor function and improved the integrity of neuromuscular junctions, MOE-modified ASO10-29 (MOE10-29) was more efficacious than morpholino-modified ASO10-29 (PMO10-29) at the same molar dose, as seen by longer survival, greater body-weight gain and better preservation of motor neurons. Time-course analysis revealed that MOE10-29 had more persistent effects than PMO10-29. On the other hand, PMO10-29 appears to more readily cross an immature blood-brain barrier following systemic administration, showing more robust initial effects on SMN2 exon 7 inclusion, but less persistence in the central nervous system. We conclude that both modifications can be effective as splice-switching ASOs in the context of SMA and potentially other diseases, and discuss the advantages and disadvantages of each