Whole-scalp EEG mapping of somatosensory evoked potentials in macaque monkeys

High-density scalp EEG recordings are widely used to study whole-brain neuronal networks in humans non-invasively. Here, we validate EEG mapping of somatosensory evoked potentials (SSEPs) in macaque monkeys (Macaca fascicularis) for the long-term investigation of large-scale neuronal networks and their reorganisation after lesions requiring a craniotomy. SSEPs were acquired from 33 scalp electrodes in five adult anaesthetized animals after electrical median or tibial nerve stimulation. SSEP scalp potential maps were identified by cluster analysis and identified in individual recordings. A distributed, linear inverse solution was used to estimate the intracortical sources of the scalp potentials. SSEPs were characterised by a sequence of components with unique scalp topographies. Source analysis confirmed that median nerve SSEP component maps were in accordance with the somatotopic organisation of the sensorimotor cortex. Most importantly, SSEP recordings were stable both intra- and interindividually. We aim to apply this method to the study of recovery and reorganisation of large-scale neuronal networks following a focal cortical lesion requiring a craniotomy. As a prerequisite, the present study demonstrated that a 300-mm2 unilateral craniotomy over the sensorimotor cortex necessary to induce a cortical lesion, followed by bone flap repositioning, suture and gap plugging with calcium phosphate cement, did not induce major distortions of the SSEPs. In conclusion, SSEPs can be successfully and reproducibly recorded from high-density EEG caps in macaque monkeys before and after a craniotomy, opening new possibilities for the long-term follow-up of the cortical reorganisation of large-scale networks in macaque monkeys after a cortical lesion

Using whole-plant chambers to estimate carbon and water fluxes in field-grown grapevines

There are limited studies available that have investigated the effects of different levels of water supply on the whole-plant gas exchange dynamics. The latter is related to the difficulty in measuring whole-canopy carbon fixation and water consumption, especially in field conditions. Whole-plant chambers can measure these fluxes, therefore the aims of this work were (i) to determine the relationship between whole-plant gas exchange compared to single leaf gas exchange; (ii) to validate whole-canopy chamber measurements using sap flow probes; (iii) to measure the effect of soil water availability on water use efficiency calculated from gas exchange measured using whole-plant chambers. For these purposes, an experiment was carried out during the 2014 season in an experimental vineyard using six-years-old plants of cv. Grenache. Two irrigation regimes were established, moderate irrigation (50 % ETo) and non-irrigation. Carbon fixation and transpiration were measured using whole-plant chambers at veraison and pre-harvest. Simultaneously, leaf gas exchange was measured at different canopy positions during the day in order to compare those measurements with the whole-plant chamber data. In parallel, sap flow measurements were continuously recorded using heat balance probes. Results showed that CO2 fixation measured at noon in sun exposed leaves oriented to the south presented the highest correlation coefficient with whole plant chamber data. Whole-plant transpiration measured with whole-plant chambers was slightly higher compared to the estimated from sap flow data in both irrigated and non-irrigated plants. In general intensive leaf-level measurements do not completely reflect the whole plant physiology, due to variability of leaf to leaf environmental conditions and plant regulation of gas exchange.This work has been developed with financial support from the Spanish Ministry of Economy project AGL2014-54201-C4-1, and the financial assistance by University of Balearic Island for visiting professors stays. We are indebted to Dr. Pérez Peña, Dr. Prieto (INTA, Argentina), and Mr. Pep Sastre (University of Balearic Island) during construction and commissioning of whole plant chambers. We would like to thank Mr. Miquel Truyols and collaborators of the UIB Experimental Field which are supported by the UIB Grant 15/2015 for their support to our experiments. We want to thanks Dr. Fuentes for English revision.Peer reviewe

Phase 2 trial of the DPP-1 inhibitor brensocatib in bronchiectasis

Background: Patients with bronchiectasis have frequent exacerbations that are thought to be related to neutrophilic inflammation. The activity and quantity of neutrophil serine proteases, including neutrophil elastase, are increased in the sputum of patients with bronchiectasis at baseline and increase further during exacerbations. Brensocatib (INS1007) is an oral reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), an enzyme responsible for the activation of neutrophil serine proteases. Methods: In a phase 2, randomized, double-blind, placebo-controlled trial, we randomly assigned, in a 1:1:1 ratio, patients with bronchiectasis who had had at least two exacerbations in the previous year to receive placebo, 10 mg of brensocatib, or 25 mg of brensocatib once daily for 24 weeks. The time to the first exacerbation (primary end point), the rate of exacerbations (secondary end point), sputum neutrophil elastase activity, and safety were assessed. Results: Of 256 patients, 87 were assigned to receive placebo, 82 to receive 10 mg of brensocatib, and 87 to receive 25 mg of brensocatib. The 25th percentile of the time to the first exacerbation was 67 days in the placebo group, 134 days in the 10-mg brensocatib group, and 96 days in the 25-mg brensocatib group. Brensocatib treatment prolonged the time to the first exacerbation as compared with placebo (P = 0.03 for 10-mg brensocatib vs. placebo; P = 0.04 for 25-mg brensocatib vs. placebo). The adjusted hazard ratio for exacerbation in the comparison of brensocatib with placebo was 0.58 (95% confidence interval [CI], 0.35 to 0.95) in the 10-mg group (P = 0.03) and 0.62 (95% CI, 0.38 to 0.99) in the 25-mg group (P = 0.046). The incidence-rate ratio was 0.64 (95% CI, 0.42 to 0.98) in the 10-mg group, as compared with placebo (P = 0.04), and 0.75 (95% CI, 0.50 to 1.13) in the 25-mg group, as compared with placebo (P = 0.17). With both brensocatib doses, sputum neutrophil elastase activity was reduced from baseline over the 24-week treatment period. The incidence of dental and skin adverse events of special interest was higher with the 10-mg and 25-mg brensocatib doses, respectively, than with placebo. Conclusions: In this 24-week trial, reduction of neutrophil serine protease activity with brensocatib in patients with bronchiectasis was associated with improvements in bronchiectasis clinical outcomes