Elastic ankle exoskeletons reduce soleus muscle force but not work in human hopping

This is the author accepted manuscript. The final version is available from the American Physiological Society via the DOI in this recordInspired by elastic energy storage and return in tendons of human leg muscle-tendon units (MTU), exoskeletons often place a spring in parallel with an MTU to assist the MTU. However, this might perturb the normally efficient MTU mechanics and actually increase active muscle mechanical work. This study tested the effects of elastic parallel assistance on MTU mechanics. Participants hopped with and without spring-loaded ankle exoskeletons that assisted plantar flexion. An inverse dynamics analysis, combined with in vivo ultrasound imaging of soleus fascicles and surface electromyography, was used to determine muscle-tendon mechanics and activations. Whole body net metabolic power was obtained from indirect calorimetry. When hopping with spring-loaded exoskeletons, soleus activation was reduced (30-70%) and so was the magnitude of soleus force (peak force reduced by 30%) and the average rate of soleus force generation (by 50%). Although forces were lower, average positive fascicle power remained unchanged, owing to increased fascicle excursion (+4-5 mm). Net metabolic power was reduced with exoskeleton assistance (19%). These findings highlighted that parallel assistance to a muscle with appreciable series elasticity may have some negative consequences, and that the metabolic cost associated with generating force may be more pronounced than the cost of doing work for these muscles.This study was in part funded by US Israel Binational Science Foundation Start Up Grant 2011152 awarded to G. S. Sawicki

Piloting data linkage in a prospective cohort study of a GP referral scheme to avoid unnecessary emergency department conveyance

BACKGROUND: UK Ambulance services are under pressure to safely stream appropriate patients away from the Emergency Department (ED). Even so, there has been little evaluation of patient outcomes. We investigated differences between patients who are conveyed directly to ED after calling 999 and those referred by an ambulance crew to a novel GP referral scheme. METHODS: This was a prospective study comparing patients from two cohorts, one conveyed directly to the ED (n = 4219) and the other referred to a GP by the on-scene paramedic (n = 321). To compare differences in patient outcomes, we include follow-up data of a smaller subset of each cohort (up to n = 150 in each) including hospital admission, history of long-term illness, previous ED attendance, length of stay, hospital investigations, internal transfers, 30-day re-admission and 10-month mortality. RESULTS: Older individuals, females, and those with minor incidents were more likely to be referred to a GP than conveyed directly to ED. Of those patients referred to the GP, only 22.4% presented at ED within 30 days. These patients were more likely to be admitted then than were those initially conveyed directly to ED (59% vs 31%). Those conveyed to ED had a higher risk of death compared to those who were referred to the GP (HR: 2.59; 95% CI 1.14–5.89), however when analyses were restricted to those who presented at ED within 30 days, there was no difference in mortality risk (HR: 1.45; 95% CI 0.58–3.65). CONCLUSIONS: Despite limited data and a small sample size, there were differences between patients conveyed directly to ED and those who were referred into GP care. Initial evidence suggests that referring individuals to a GP may provide an appropriate and safe alternative path of care. This pilot study demonstrated a need for larger scale, methodologically rigorous study to demonstrate the benefits of alternative conveyance schemes and recommend changes to the current system of urgent and emergency care

Fish reproductive-energy output increases disproportionately with body size

This is the author accepted manuscript. The final version is available from the American Association for the Advancement of Science via the DOI in this record All data, metadata, and R code can be downloaded and cited as “D. R. Barneche, D. R. Robertson, C. R. White, D. J. Marshall, Data and code from: Fish reproductive-energy output increases disproportionately with body size. Zenodo (available at https:// github.com/dbarneche/fishFecundity), doi:10.5281/zenodo.1213118.”Body size determines total reproductive-energy output. Most theories assume reproductive output is a fixed proportion of size, with respect to mass, but formal macroecological tests are lacking. Management based on that assumption risks underestimating the contribution of larger mothers to replenishment, hindering sustainable harvesting. We test this assumption in marine fishes with a phylogenetically controlled meta-analysis of the intraspecific mass scaling of reproductive-energy output. We show that larger mothers reproduce disproportionately more than smaller mothers in not only fecundity but also total reproductive energy. Our results reset much of the theory on how reproduction scales with size and suggest that larger mothers contribute disproportionately to population replenishment. Global change and overharvesting cause fish sizes to decline; our results provide quantitative estimates of how these declines affect fisheries and ecosystem-level productivity.Centre for Geometric Biology, Monash Universit

New horizons for newborn brain protection: enhancing endogenous neuroprotection.

Intrapartum-related events are the third leading cause of childhood mortality worldwide and result in one million neurodisabled survivors each year. Infants exposed to a perinatal insult typically present with neonatal encephalopathy (NE). The contribution of pure hypoxia-ischaemia (HI) to NE has been debated; over the last decade, the sensitising effect of inflammation in the aetiology of NE and neurodisability is recognised. Therapeutic hypothermia is standard care for NE in high-income countries; however, its benefit in encephalopathic babies with sepsis or in those born following chorioamnionitis is unclear. It is now recognised that the phases of brain injury extend into a tertiary phase, which lasts for weeks to years after the initial insult and opens up new possibilities for therapy.There has been a recent focus on understanding endogenous neuroprotection and how to boost it or to supplement its effectors therapeutically once damage to the brain has occurred as in NE. In this review, we focus on strategies that can augment the body's own endogenous neuroprotection. We discuss in particular remote ischaemic postconditioning whereby endogenous brain tolerance can be activated through hypoxia/reperfusion stimuli started immediately after the index hypoxic-ischaemic insult. Therapeutic hypothermia, melatonin, erythropoietin and cannabinoids are examples of ways we can supplement the endogenous response to HI to obtain its full neuroprotective potential. Achieving the correct balance of interventions at the correct time in relation to the nature and stage of injury will be a significant challenge in the next decade

Arterial Recanalization for Access for Arterial Intervention in Children: Techniques and Outcomes

PURPOSE: To assess technical success of arterial recanalization in children requiring repeated arterial access and intervention. MATERIALS AND METHODS: Over 14 years, 41 attempts to cross 30 arterial occlusions were made in 22 patients (13 male, 9 female). Median patient age was 12 months (15 days-14 years), and weight was 7.6 kg (3.0-77.3 kg). Techniques and outcomes were recorded. RESULTS: Twenty-five of 41 (61%) attempts at crossing an arterial occlusion were successful. Nineteen of 30 (63%) first attempts to cross occlusions were successful, and 6 of 11 (55%) repeat attempts were successful. The occluded segments were combinations of common femoral artery (n = 4), external iliac artery (n = 36), common iliac artery (n = 11), and aorta (n = 1). Complications occurred in 5 of 41(12%) attempts: 3 minor complications (hematoma, extravasation, and transient leg ischemia) and 2 major complications (rupture and thrombosis). CONCLUSIONS: Arterial access by recanalization of occluded segments is technically feasible in children, with a low complication rate

Melatonin for neonatal encephalopathy: From bench to bedside

Neonatal encephalopathy is a leading cause of morbidity and mortality worldwide. Alt-hough therapeutic hypothermia (HT) is now standard practice in most neonatal intensive care units in high resource settings, some infants still develop long-term adverse neurological sequelae. In low resource settings, HT may not be safe or efficacious. Therefore, additional neuroprotective interventions are urgently needed. Melatonin’s diverse neuroprotective properties include antioxidant, anti-inflammatory, and anti-apoptotic effects. Its strong safety profile and compelling preclinical data suggests that melatonin is a promising agent to improve the outcomes of infants with NE. Over the past decade, the safety and efficacy of melatonin to augment HT has been studied in the neonatal piglet model of perinatal asphyxia. From this model, we have observed that the neuroprotective effects of melatonin are time-critical and dose dependent. Therapeutic melatonin levels are likely to be 15–30 mg/L and for optimal effect, these need to be achieved within the first 2–3 h after birth. This review summarises the neuroprotective properties of melatonin, the key findings from the piglet and other animal studies to date, and the challenges we face to translate melatonin from bench to bedside

Fulvestrant: pharmacokinetics and pharmacology

Fulvestrant is a new type of oestrogen receptor (ER) antagonist with no agonist activity and a novel pharmacological profile. Fulvestrant has been shown to significantly reduce cellular levels of the ER and progesterone receptor in both preclinical studies and in clinical trials of postmenopausal women with primary breast cancer. This paper reviews the pharmacokinetics and metabolism of fulvestrant, which support the rationale for drug delivery as a single, once-monthly intramuscular injection, and show that this agent has minimal potential to be the subject, or cause, of significant cytochrome p450-mediated drug interactions