Automatic activies of the spinal cord concerned with the respiratory movements

1. After spinal transection at the medulla-spinal junction the thoracic respiratory movements no longer appear in the adult animals, nevertheless the sporadic spike discharges can be recorded from the intercostal muscles. 2. Both in the acute and chronic experiments the spinal cord is transected at the two levels of Th7 and Thl1 respectively and all the dorsal rootlets coming into that part of the cord lying between the transections are severed. The sporadic spike discharges with irregular intervals varying about 0.5 to 3.0 sec. can be recorded from intercostal muscles in the 8th to 10th segments of the spinal cord isolated. There can never be found any reflex influence of the skin stimulation upon the discharges, which also disappear provided the intercostal nerves innervating the muscles are severed. 3. From these results it may be concluded that the spinal cord is endowed with an ability to initiate the impulses autochthonously to excite the intercostal muscles, even though it is only poorly developed in the adult animals.</p

Crown ether modified peptide interactions with model membranes

A simple model of an uncharged antimicrobial peptide, carrying four crown ether side chains, is modified further by the selective incorporation of arginine side chains to control its secondary structure and its interaction with model membranes and living cells. Conformational studies show that shifting the position of a cationic residue in the peptide sequence allows to control its secondary structure and supramolecular self-assembly in solution. Results also demonstrate that the secondary structure influences the interaction with model membranes and cells. An α-helical peptide with greater amphiphilicity forms assemblies that interact with both prokaryotic and eukaryotic model membranes and cells. However, a β-stranded peptide with evenly distributed charges generates assemblies that interact more selectively with prokaryotic model membranes and cells. In addition, we observed differences in peptide orientation between uncharged and cationic α-helical peptides with different phospholipid bilayers. In general, the studied peptides have a higher affinity for thinner membranes, and cationic peptides interacted better with anionic membranes

Classification grid and evidence matrix for evaluating digital medical devices under the European union landscape

A uniform and harmonised taxonomy of Digital Medical Devices (DMDs) and their evidence-based evaluation are essential to ensure their integration into healthcare systems across the European Union (EU). As part of the Taskforce for Harmonised Evaluation of DMDs, a Common European Classification Grid for DMDs (CEUGrid-DMD) associated with an Evidence Matrix is developed. These tools are based on the mapping of existing frameworks, a survey of Health Technology Assessment (HTA) practices, consensus meetings and workshop. The survey was sent to 32 national representatives of HTA bodies from 18 EU countries. Ten HTA bodies from nine countries completed the survey while others could not, in the absence of the effective implementation of a DMD evaluation framework. This work results in the CEUGrid-DMD including four taxonomy categories, associated with an evidence-based matrix. Overall, this first version should help to converge scientific assessments of DMDs in the context of HTA Regulations across the EU

Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial

Trastuzumab deruxtecan (T-DXd) intracranial activity has been observed in small or retrospective patient cohorts with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (mBC) and stable or active (untreated/previously treated and progressing) brain metastases (BMs). The phase 3b/4 DESTINY-Breast12 study investigated T-DXd in patients with HER2+ mBC and is, to our knowledge, the largest prospective study of T-DXd in patients with BMs in this setting. Patients (stable/active BMs (n = 263) and no BMs (n = 241)) treated with one or more prior anti-HER2–based regimens received T-DXd (5.4 mg per kg). Primary endpoints were progression-free survival (PFS; BMs cohort) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (non-BMs cohort). Additional endpoints included central nervous system (CNS) PFS, ORR, time to second progression, CNS ORR (BMs cohort), incidence of new symptomatic CNS metastases (non-BMs cohort), time to progression, duration of response, overall survival and safety (both cohorts). No formal hypothesis testing was conducted for this single-arm, open-label study. In the BMs cohort, 12-month PFS was 61.6% (95% confidence interval (CI): 54.9–67.6), and 12-month CNS PFS was 58.9% (95% CI: 51.9–65.3). In the non-BMs cohort, ORR was 62.7% (95% CI: 56.5–68.8). Grade 3 or higher adverse events occurred in 51% (BMs cohort) and 49% (non-BMs cohort) of patients. Investigator-reported interstitial lung disease/pneumonitis occurred in 16% (grade ≥3: 3%) of patients with BMs and 13% (grade ≥3: 1%) of patients without BMs. These data show substantial and durable overall and intracranial activity for T-DXd, supporting its use in previously treated patients with HER2+ mBC irrespective of stable/active baseline BMs. ClinicalTrials.gov identifier: NCT04739761

Marginal Cost versus Average Cost Pricing with Climatic Shocks in Senegal: A Dynamic Computable General Equilibrium Model Applied to Water

The model simulates on a 20-year horizon, a first phase of increase in the water resource availability taking into account the supply policies by the Senegalese government and a second phase with hydrologic deficits due to demand evolution (demographic growth). The results show that marginal cost water pricing (with a subsidy ensuring the survival of the water production sector) makes it possible in the long term to absorb the shock of the resource shortage, GDP, investment and welfare increase. Unemployment drops and the sectors of rain rice, market gardening and drinking water distribution grow. In contrast, the current policy of average cost pricing of water leads the long-term economy in a recession with an agricultural production decrease, a strong degradation of welfare and a rise of unemployment. This result questions the basic tariff (average cost) on which block water pricing is based in Senegal

Classical decomposition of Markowitz portfolio selection

In this study, we enhance Markowitz portfolio selection with graph theory for the analysis of two portfolios composed of either EU or US assets. Using a threshold-based decomposition of their respective covariance matrices, we perturb the level of risk in each portfolio and build the corresponding sets of graphs. We show that the "superimposition" of all graphs in a set allows for the (re)construction of the efficient frontiers. We also identify a relationship between the Sharpe ratio (SR) of a given portfolio and the topology of the corresponding network of assets. More specifically, we suggest SR = f(topology) ≈ f(ECC/BC), where ECC is the eccentricity and BC is the betweenness centrality averaged over all nodes in the network. At each threshold, the structural analysis of the correlated networks provides unique insights into the relationships between assets, agencies, risks, returns and cash flows. We observe that the best threshold or best graph representation corresponds to the portfolio with the highest Sharpe ratio. We also show that simulated annealing performs better than a gradient-based solver

Adsorption of water molecules on oxidized graphite surfaces: A molecular dynamics study of the competition between OH and COOH sites

International audienceIn this paper, molecular dynamic simulations are used to study the adsorption of water molecules on partially oxidized graphite surfaces containing COOH and OH sites. More specially, the competition between the OH and COOH sites with respect to water adsorption is characterized at three different temperatures (200, 250 and 300 K). The simulations show a strong preferential clustering of the water molecules around the COOH sites irrespective of the temperature. The present results also show that the OH sites can influence the water adsorption process at high temperature, if their local density on the surface is sufficiently large. In this situation, the dynamics of the adsorption process is shown to depend on the distribution of these OH sites on the surface. These results give insights into the water adsorption mechanisms on oxidized graphite surfaces constituting, for example, black carbons or soot particles emitted by aircraft

A new semi-empirical model for the oxidation of PAHs physisorbed on soot. I. Application to the reaction C6H6 + OH.

International audienceIn the present paper, we have used a new semi-empirical method to characterize the oxidation by OH of a benzene molecule adsorbed on a soot surface modelled by a graphene-like cluster. This method is based on an electrostatic and induction contribution calculated at the SCF AM1 level associated with a sum of two-body dispersion terms of the C6/R6 form. This so-called AM1-D method has been used to compare the characteristics of the oxidation reaction for the adsorbed benzene with those of the corresponding reaction in the gas phase. The main conclusion of the present work is a clear inhibition of the oxidation process by the adsorption of the benzene molecule on the soot surface. This conclusion is in qualitative agreement with experimental observations, concerning however larger PAH molecules