Effect of Interfacial SiOx Defects on the Functional Properties of Si-Transition Metal Oxide Photoanodes for Water Splitting.

The transfer of photogenerated charges through interfaces in heterojunction photoanodes is a key process that controls the efficiency of solar water splitting. Considering Co3O4/SiOx/Si photoanodes prepared by physical vapor deposition as a representative case study, it is shown that defects normally present in the native SiOx layer dramatically affect the onset of the photocurrent. Electron paramagnetic resonance indicates that the signal of defects located in dangling bonds of trivalent Si atoms at the Si/SiOx interface vanishes upon vacuum annealing at 850 °C. Correspondingly, the photovoltage of the photoanode increases to ≈500 mV. Similar results are obtained for NiO/SiOx/Si photoanodes. Photoelectrochemical analysis and impedance spectroscopy (in solution and in the solid state) indicate how the defect annealing modifies the Co3O4/SiOx/Si junction. This work shows that defect annealing at the solid-solid interface in composite photoanodes strongly improves the efficiency of charge transfer through interfaces, which is the basis for effective solar-to-chemical energy conversion.

Magnetoencephalography reveals differences in brain activations for fast and slow responses to simple multiplications.

Despite decades of studies, it is still an open question on how and where simple multiplications are solved by the brain. This fragmented picture is mostly related to the different tasks employed. While in neuropsychological studies patients are asked to perform and report simple oral calculations, neuroimaging and neurophysiological studies often use verification tasks, in which the result is shown, and the participant must verify the correctness. This MEG study aims to unify the sources of evidence, investigating how brain activation unfolds in time using a single-digit multiplication production task. We compared the participants' brain activity-focusing on the parietal lobes-based on response efficiency, dividing their responses in fast and slow. Results showed higher activation for fast, as compared to slow, responses in the left angular gyrus starting after the first operand, and in the right supramarginal gyrus only after the second operand. A whole-brain analysis showed that fast responses had higher activation in the right dorsolateral prefrontal cortex. We show a timing difference of both hemispheres during simple multiplications. Results suggest that while the left parietal lobe may allow an initial retrieval of several possible solutions, the right one may be engaged later, helping to identify the solution based on magnitude checking.

Monolayer doping of germanium by phosphorus-containing molecules.

The DPP (diethyl 1-propylphosphonate) and ODPA (octadecylphosphonic acid) molecules are studied as precursors for the monolayer doping (MLD) of germanium. Their adsorption behaviour is investigated, revealing different physicochemical interactions between the phosphorus-containing molecules and the Ge surfaces. It is discovered that DPP adsorption occurs after the oxidation of Ge surface, while the ODPA undergoes chemisorption on -H terminated surfaces. Quantitative phosphorus analysis demonstrates that in the first case more than one monolayer is formed (from 2 to 4), while in the second a single monolayer is formed. Moreover, the analysis of phosphorus diffusion from the surface layers into the Ge matrix reveals that conventional thermal annealing processes are not suitable for Ge injection due to a higher activation energy of the process in comparison with silicon. On the contrary, pulsed laser melting is effective in forming a doped layer, owing to the precursor's decomposition under UV light.

Phase III safety study of intravenous NEPA: a novel fixed antiemetic combination of fosnetupitant and palonosetron in patients receiving highly emetogenic chemotherapy.

Background: NEPA, an oral fixed combination of the NK1RA netupitant (300 mg) and clinically/pharmacologically distinct 5-HT3RA palonosetron (PALO, 0.50 mg), is the first fixed antiemetic combination to have been approved. A single oral NEPA capsule plus dexamethasone (DEX) given before anthracycline-cyclophosphamide (AC) and non-AC highly emetogenic chemotherapy (HEC) showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) over PALO plus DEX for 5 days postchemotherapy. The safety of NEPA was well-established in the phase II/III clinical program in 1169 NEPA-treated patients. An intravenous (i.v.) formulation of the NEPA combination (fosnetupitant 235 mg plus PALO 0.25 mg) has been developed. Patients and methods: This randomized, multinational, double-blind, stratified (by sex and country) phase III study (NCT02517021) in chemotherapy-naïve patients with solid tumors assessed the safety of a single dose of i.v. NEPA infused over 30 min before initial and repeated cycles of HEC. Patients received either i.v. NEPA or oral NEPA, both with oral DEX on days 1-4. Safety was assessed primarily by treatment-emergent adverse events (AEs) and electrocardiograms. Results: A total of 404 patients completed 1312 cycles. The incidence and type of treatment-emergent AEs were similar for both treatment groups with the majority of AEs as mild/moderate in intensity. There was no increased incidence of AEs in subsequent cycles in either group. The incidence of treatment-related AEs was similar and relatively low in both groups (12.8% i.v. NEPA and 11.4% oral NEPA during the entire study), with constipation being the most common (6.4% i.v. NEPA, 6.0% oral NEPA). No serious treatment-related AEs occurred in either group. No infusion site or anaphylactic reactions related to i.v. NEPA occurred. No clinically relevant changes in QTc and no cardiac safety concerns were observed. Conclusions: Intravenous NEPA was well-tolerated with a similar safety profile to oral NEPA in patients with various solid tumors receiving HEC.

Magnetoresistive sensors for measurements of DNA hybridization kinetics - effect of TINA modifications.

We present the use of magnetoresistive sensors integrated in a microfluidic system for real-time studies of the hybridization kinetics of DNA labeled with magnetic nanoparticles to an array of surface-tethered probes. The nanoparticles were magnetized by the magnetic field from the sensor current. A local negative reference ensured that only the specific binding signal was measured. Analysis of the real-time hybridization using a two-compartment model yielded both the association and dissociation constants kon, and koff. The effect of probe modifications with ortho-Twisted Intercalating Nucleic Acid (TINA) was studied. Such modifications have been demonstrated to increase the melting temperature of DNA hybrids in solution and are also relevant for surface-based DNA sensing. Kinetic data for DNA probes with no TINA modification or with TINA modifications at the 5' end (1 × TINA) or at both the 5' and 3' ends (2 × TINA) were compared. TINA modifications were found to provide a relative decrease of koff by a factor of 6-20 at temperatures from 57.5 °C to 60 °C. The values of kon were generally in the range between 0.5-2 × 105 M-1s-1 and showed lower values for the unmodified probe than for the TINA modified probes. The observations correlated well with measured melting temperatures of the DNA hybrids.

Unfavorable Donor Pretransplant APACHE II, SAPS II, and SOFA Scores Are Not Associated With Outcome: Implications for Heart Transplant Donor Selection.

BACKGROUND: The quality of the donor heart and the individual risk of the recipient awaiting heart transplantation are difficult to assess. We investigated whether routinely used intensive care scoring systems can provide additional prognostic information on outcomes after heart transplantation. METHODS: A total of 114 consecutive patients who underwent heart transplantation were included. The Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score (SAPS II), and the Sequential Organ Failure Assessment (SOFA) scores were calculated for donors and recipients. Risk factors such as the donor's cause of death, donor's catecholamine use, dialysis status of the recipient, and smoking pattern of the donor and the recipient were assessed. The association of these parameters with mortality, length of stay on the intensive care unit, and need for invasive ventilation was investigated. RESULTS: The median APACHE II score of the donors was 20 (confidence interval [CI], 19-20), the median SAPS II score was 46 (CI, 45-48), and the median SOFA score was 10 (CI, 9-10). In contrast, the median scores of the recipients were as follows: APACHE II, 7 (CI, 6-8); SAPS II, 13 (CI, 12-14); and SOFA, 1 (CI, 1-2). None of the scores as calculated significantly predicted clinical outcome after transplantation. CONCLUSIONS: This study detected no prognostic impact of donor-related risk factors on outcome after heart transplantation. Our findings support the growing practice of also considering organs from donors with high-risk scores for heart transplantation.

Pharyngeal spasticity due to dantrolene.

WHAT IS KNOWN AND OBJECTIVE: Dantrolene can be combined with baclofen to better treat spasticity, but may cause muscular weakness and dysphagia. We instead describe a pharyngeal spasm due to dantrolene. CASE SUMMARY: A 12-year-old male received dantrolene 3 mg/kg/day in adjunct to baclofen 2 mg/kg/day, to improve spasticity. After 5 days of full-dose dantrolene, his dysphagia worsened and he developed pharyngeal spasm. Dantrolene was suspected for an adverse reaction and removed. The patient subsequently improved. WHAT IS NEW AND CONCLUSION: Causality analysis determined a probable relationship between dantrolene and pharyngeal spasm. This may be due to direct muscle contraction by dantrolene, an effect seen previously in vitro.

A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy.

BACKGROUND: Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, which targets dual antiemetic pathways. PATIENTS AND METHODS: This multinational, randomized, double-blind, parallel group phase III study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline-cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy end point was complete response (CR: no emesis, no rescue medication) during the delayed (25-120 h) phase in cycle 1. RESULTS: The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% versus 69.5%; P = 0.001), as were the percentages in the overall (0-120 h) (74.3% versus 66.6%; P = 0.001) and acute (0-24 h) (88.4% versus 85.0%; P = 0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy end points of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO. CONCLUSIONS: NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of DEX on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.

Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study.

BACKGROUND: NEPA is a novel oral fixed-dose combination of netupitant (NETU), a new highly selective neurokinin-1 (NK1) receptor antagonist (RA) and palonosetron (PALO), a pharmacologically and clinically distinct 5-hydroxytryptamine type 3 (5-HT3) RA. This study was designed to determine the appropriate clinical dose of NETU to combine with PALO for evaluation in the phase 3 NEPA program. PATIENTS AND METHODS: This randomized, double-blind, parallel group study in 694 chemotherapy naïve patients undergoing cisplatin-based chemotherapy for solid tumors compared three different oral doses of NETU (100, 200, and 300 mg) + PALO 0.50 mg with oral PALO 0.50 mg, all given on day 1. A standard 3-day aprepitant (APR) + IV ondansetron (OND) 32 mg regimen was included as an exploratory arm. All patients received oral dexamethasone on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0-120 h) phase. RESULTS: All NEPA doses showed superior overall CR rates compared with PALO (87.4%, 87.6%, and 89.6% for NEPA100, NEPA200, and NEPA300, respectively versus 76.5% PALO; P < 0.050) with the highest NEPA300 dose studied showing an incremental benefit over lower NEPA doses for all efficacy endpoints. NEPA300 was significantly more effective than PALO and numerically better than APR + OND for all secondary efficacy endpoints of no emesis, no significant nausea, and complete protection (CR plus no significant nausea) rates during the acute (0-24 h), delayed (25-120 h), and overall phases. Adverse events were comparable across groups with no dose response. The percent of patients developing electrocardiogram changes was also comparable. CONCLUSIONS: Each NEPA dose provided superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with PALO following highly emetogenic chemotherapy; however, NEPA300 was the best dose studied, with an advantage over lower doses for all efficacy endpoints. The combination of NETU and PALO was well tolerated with a similar safety profile to PALO and APR + OND.

A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy.

BACKGROUND: Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC. PATIENTS AND METHODS: This multinational, double-blind, randomized phase III study (NCT01376297) in 413 chemotherapy-naïve patients evaluated a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1-4 and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue). RESULTS: Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) with 75% completing ≥4 cycles. The incidence/type of AEs was comparable for both groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache (1.0%); there was no indication of increasing AEs over multiple cycles. The majority of AEs were mild/moderate and there were no cardiac safety concerns based on AEs and electrocardiograms. The overall (0-120 h) CR rates in cycle 1 were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy was maintained over repeated cycles. CONCLUSIONS: NEPA, a convenient single oral dose antiemetic targeting dual pathways, was safe, well tolerated and highly effective over multiple cycles of HEC/MEC.

Green synthesis and electrophoretic deposition of Ag nanoparticles on SiO2/Si(100).

Plasmonic substrates were prepared by electrophoretic deposition of Ag nanoparticles on SiO2/Si(100). The Ag nanoparticles were obtained using [Ag(NH3)2](+) as the Ag precursor and d-glucose as the reducing agent. Under optimized conditions, this simple and green synthesis method furnished a suspension of Ag nanoparticles with a narrow dimensional dispersion (centered around 27 nm) and a negative z-potential, suitable for electrophoretic deposition. Samples were chemically, optically and morphologically characterized by photoemission and UV-vis spectroscopy and electron microscopy, and tested as substrates for surface enhanced Raman spectroscopy. Despite being a very simple procedure, good enhancement factors were measured thanks to the formation of hot spots, formed by sandwiching the analyte (benzenethiol) between sequentially deposited Ag nanoparticles.

Measurements of Brownian relaxation of magnetic nanobeads using planar Hall effect bridge sensors.

We compare measurements of the Brownian relaxation response of magnetic nanobeads in suspension using planar Hall effect sensors of cross geometry and a newly proposed bridge geometry. We find that the bridge sensor yields six times as large signals as the cross sensor, which results in a more accurate determination of the hydrodynamic size of the magnetic nanobeads. Finally, the bridge sensor has successfully been used to measure the change in dynamic magnetic response when rolling circle amplified DNA molecules are bound to the magnetic nanobeads. The change is validated by measurements performed in a commercial AC susceptometer. The presented bridge sensor is, thus, a promising component in future lab-on-a-chip biosensors for detection of clinically relevant analytes, including bacterial genomic DNA and proteins.

Growth and optical properties of silver nanostructures obtained on connected anodic aluminum oxide templates.

Ag nanostructures are grown by AC electrodeposition on anodic alumina oxide (AAO) connected membranes acting as templates. Depending on the thickness of the template and on the voltage applied during the growth process, different Ag nanostructures with different optical properties are obtained. When AAO membranes about 1 µm thick are used, the Ag nanostructures consist in Ag nanorods, at the bottom of the pores, and Ag nanotubes departing from the nanorods and filling the pores almost for the whole length. When AAO membranes about 3 µm thick are used, the nanostructures are Ag spheroids, at the bottom of the pores, and Ag nanowires that do not reach the upper part of the alumina pores. The samples are characterized by angle resolved x-ray photoelectron spectroscopy, scanning electron microscopy and UV-vis and Raman spectroscopies. A simple NaOH etching procedure, followed by sonication in ethanol, allows one to obtain an exposed ordered array of Ag nanorods, suitable for surface-enhanced Raman spectroscopy, while in the other case (3 µm thick AAO membranes) the sample can be used in localized surface plasmon resonance sensing.

Biomedical coatings to improve the tissue-biomaterial interface.

One of the most important factors determining the degree of tissue interaction of an implanted device is the property of its surface. Thus, great importance is given to chemical and morphological characteristics of biomaterial surfaces to improve biocompatibility, cell migration, proliferation and differentiation, mechanical stability and endogenous tissue ingrowth. In order to obtain new and healing stimulating properties, it is possible to apply a coating or more generally a surface treatment to the surface of a prosthetic device. One of the most versatile methods for coating is thermal spray technology. This paper considers the principle of thermal spray processes and their application in the biomedical field, namely the coatings used for orthopedic prostheses and dental implants. Among thermal spray processes, plasma spray as well as High Velocity Oxygen Fuel (HVOF) processes will be particularly considered and their most important aspects will be illustrated.

Phase-contrast microtomography of thin biomaterials.

Phase-contrast microtomography, performed at the beamline ID 22 of the European Synchrotron Radiation Facility (ESRF, Grenoble, France), is demonstrated for high-resolution 3-D imaging of a hydroxyapatite sample. The technique, which relies on phase contrast imaging, gives the possibility to observe features inside samples with negligible absorption contrast. The positive results obtained suggest a possible future investigation of the influence of the distribution of pores and defects inside biomaterial coatings, on the growth of osteoblast cells.

Biologic effects of surface roughness and fluorhydroxyapatite coating on osteointegration in external fixation systems: an in vivo experimental study.

The concomitant influence of surface roughness and fluorhydroxyapatite (FHA) coating of titanium (Ti) implants on bone response was investigated. For this purpose, titanium screw-shaped implants with a lower degree (Y371) and a higher degree (TiPore300) of surface roughness, coated with FHA and uncoated, were transversally inserted into the diaphyses of sheep tibiae for 12 weeks. Four sheep received Y371 (group A) and Y371 + FHA (group B) screws and four sheep received TiPore300 (group C) and TiPore300 + FHA (group D) screws. For each type of material, the morphology and microstructure of implant-facing bone were evaluated. The host bone of each tibia was used as a control. In all groups the bone tissue did not reach a complete maturation. The higher degree of roughness, perhaps due to an excessive irregularity of the surface, induced the worst osteointegration: a fibrous tissue layer between screw and new bone tissue was often present. Nevertheless, as viewed by XRD, no crystallographic change of the apatite lattice was observed in any of the implants. In contrast, the microhardness value, an index of bone mineralization, was higher in the uncoated screws and decreased progressively in the following order: group C > group A > group B > group D. The association of plasma spraying with roughness treatment constitutes a complex system that seems to interfere with bone mineralization. A chemical change of the surface, perhaps with more Ti release or more coating degradation, could be responsible for such impairment. The authors emphasize the necessity for simultaneous evaluation of surface topography and chemistry as well as an improvement in plasma-spraying and post-processing techniques and in standard procedures for materials characterization.

Biomechanical and histomorphometric investigations on two morphologically differing titanium surfaces with and without fluorohydroxyapatite coating: an experimental study in sheep tibiae.

The influence of fluorohydroxyapatite (FHA) coating and surface roughness of Ti6Al4V implants on bone response was investigated. Uncoated and FHA-coated screws with lower (LR and LR+FHA; Ra: 5.7+/-0.2 microm) and higher (HR and HR+FHA; Ra: 21.8+/-0.9 microm) surface roughness, were inserted into the diaphyses of 8 sheep tibiae. Twelve weeks after implantation, extraction torque and bone-to-implant contact were evaluated. The smoothest surfaces showed an improved extraction torque and significant differences were observed between LR and HR (-24.6%, p<0.0005), LR and HR+FHA (-30.7%, p<0.0005), LR+FHA and HR (-17.4%, p<0.005), and LR+FHA and HR+FHA (-24.0%, p<0.005). The bone-to-implant contact data paralleled the biomechanical data: the smoother the surface, the greater the bone-to-implant contact. Significant (p<0.0005) decreases in bone-to-implant contact were observed between LR+FHA and HR (-24.2%), and between LR+FHA and HR+FHA (-29.2%). The current findings suggest that LR surfaces significantly improve the osteointegration rate of implanted cortical screws independently of the FHA coating.

Design, characterization, and structure of a biologically active single-chain mutant of human IFN-gamma.

A mutant form of human interferon-gamma (IFN-gamma SC1) that binds one IFN-gamma receptor alpha chain (IFN-gamma R alpha) has been designed and characterized. IFN-gamma SC1 was derived by linking the two peptide chains of the IFN-gamma dimer by a seven-residue linker and changing His111 in the first chain to an aspartic acid residue. Isothermal titration calorimetry shows that IFN-gamma SC1 forms a 1:1 complex with its high-affinity receptor (IFN-gamma R alpha) with an affinity of 27(+/- 9) nM. The crystal structure of IFN-gamma SC1 has been determined at 2.9 A resolution from crystals grown in 1.4 M citrate solutions at pH 7.6. Comparison of the wild-type receptor-binding domain and the Asp111-containing domain of IFN-gamma SC1 show that they are structurally equivalent but have very different electrostatic surface potentials. As a result, surface charge rather than structural changes is likely responsible for the inability of the His111-->Asp domain of to bind IFN-gamma R alpha. The AB loops of IFN-gamma SC1 adopt conformations similar to the ordered loops of IFN-gamma observed in the crystal structure of the IFN-gamma/IFN-gamma R alpha complex. Thus, IFN-gamma R alpha binding does not result in a large conformational change in the AB loop as previously suggested. The structure also reveals the final six C-terminal amino acid residues of IFN-gamma SC1 (residues 253-258) that have not been observed in any other reported IFN-gamma structures. Despite binding to only one IFN-gamma R alpha, IFN-gamma SC1 is biologically active in cell proliferation, MHC class I induction, and anti-viral assays. This suggests that one domain of IFN-gamma is sufficient to recruit IFN-gamma R alpha and IFN-gamma R beta into a complex competent for eliciting biological activity. The current data are consistent with the main role of the IFN-gamma dimer being to decrease the dissociation constant of IFN-gamma for its cellular receptors.