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Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD.To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation.Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791).Outpatient.150 patients with PD and constipation.ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period.The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]).The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (Longer treatment periods need to be investigated in future studies.ENT-01 was safe and significantly improved constipation.Enterin, Inc.

Supplementary Table 1 from Identification of Nicotinamide N-Methyltransferase as a Novel Serum Tumor Marker for Colorectal Cancer

Purpose: The goal of this study was to identify and validate novel serum markers of human colorectal cancer as potential candidates for noninvasive detection of early colorectal neoplasm.Experimental Design: Employing two-dimensional gel electrophoresis and mass spectrometry, we analyzed 16 matched colorectal cancer and adjacent normal tissue samples. Proteins found to be elevated in cancer tissue were further validated by generating antibodies which were used for immunoblotting of tissue samples and for the development of highly sensitive immunoassays for assessment of serum samples.Results: In total, 735 different proteins were identified in colon tissue. Strong elevation in colorectal cancer for five proteins was confirmed by immunoblot analysis: transforming growth factor-β induced protein ig-h3 (βIG-H3), nicotinamide N-methyltransferase (NNMT), nucleoside diphosphate kinase A (nm23-H1), purine nucleoside phosphorylase (PNPH), and mannose-6-phosphate receptor binding protein 1 (M6P1). Elevated levels of NNMT, which is not predicted to be secreted but is known as a cytoplasmic protein, were found in serum from patients with colorectal cancer. Employing a receiver-operating characteristic curve based on the measurement of 109 patients with colorectal cancer and 317 healthy controls, we obtained an area under the curve of 0.84 for NNMT, which was superior to the established tumor marker carcinoembryogenic antigen with an area under the curve of 0.78.Conclusions: It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.

Introduction We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). Methods Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. Results The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). Discussion PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.

SummaryMR1T lymphocytes are a recently identified population of T cells that recognize unknown self-antigens presented by the non-polymorphic MHC-I-related molecule, MR1. MR1T cells can kill tumor cells and modulate the functions of other immune cells with promising therapeutic applications. By integrating genetic, pharmacological and biochemical approaches we identified carbonyl stress and alterations of nucleobase metabolism in tumor target cells that promote recognition by MR1 T cells. We dissected these pathways and found that nucleobase adduct-containing metabolites are self-antigens stimulating MR1T cells. Several nucleobase adducts are presented by MR1 molecules and stimulate individual MR1T cells. Our data suggest that MR1T cells are surveyor of cellular metabolic alterations occurring in conditions of metabolic stress, such as cancer, and lay the groundwork for the development of novel HLA-unrestricted T cell-based therapies.

Introduction This phase 2b/3 trial examined the effects of plasma exchange (PE) in patients with mild‐to‐moderate Alzheimer's disease (AD). Methods Three hundred forty‐seven patients (496 screened) were randomized (1:1:1:1) into three PE treatment arms with different doses of albumin and intravenous immunoglobulin replacement (6‐week period of weekly conventional PE followed by a 12‐month period of monthly low‐volume PE), and placebo (sham). Results PE‐treated patients performed significantly better than placebo for the co‐primary endpoints: change from baseline of Alzheimer's Disease Cooperative Study–Activities of Daily Living (ADCS‐ADL; P = .03; 52% less decline) with a trend for Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS‐Cog; P = .06; 66% less decline) scores at month 14. Moderate‐AD patients (baseline Mini‐Mental State Examination [MMSE] 18‐21) scored better on ADCS‐ADL (P = .002) and ADAS‐Cog (P = .05), 61% less decline both. There were no changes in mild‐AD patients (MMSE 22‐26). PE‐treated patients scored better on the Clinical Dementia Rating Sum of Boxes (CDR‐sb) (P = .002; 71% less decline) and Alzheimer's Disease Cooperative Study‐Clinical Global Impression of Change (ADCS‐CGIC) (P

Data on the efficacy and safety of the combination of warfarin and dual-antiplatelet therapy compared with warfarin and mono-antiplatelet therapy (MAPT) in patients with left ventricular assist devices (LVAD) remains scarce. Single-center study of 130 consecutive patients with durable LVAD. Baseline demographics, antithrombotic and antiplatelet regimen, and outcomes were compared between patients receiving warfarin plus dual-antiplatelet therapy (Group 1) and warfarin plus MAPT (Group 2). Antiplatelet therapy was assessed at hospital discharge post-LVAD implant and included aspirin, clopidogrel and dipyridamole. Outcomes at 1-year were assessed in each group. All patients were on aspirin and warfarin. No significant differences with regards to age, gender or ethnicity were noted at baseline between the two groups. Group 1 was more likely to have higher lactate dehydrogenase LDH levels at discharge and a history of stroke. No significant differences in international normalized ratio INR, hemoglobin or hematocrit were noted at discharge. During the study period, 48 patients had gastrointestinal bleeding events: 28 of 68 (41.2%) in Group 1 vs 20 of 62 (32.2%) in Group 2 (P = 0.293). At 1year, no statistically significant differences were noted in gastrointestinal bleeding (Group 1=27.90% vs Group 2 = 25.80, P = 0.784), ischemic stroke (Group 1 = 8.8% vs group 2 = 6.5%, P = 0.612), hemorrhagic stroke (Group 1 = 4.4% vs group 2 = 3.2%, P = 0.725) or mortality (Group 1 = 5.9% vs Group 2 = 1.6%, P = 0.206). Rates of pump thrombosis however were lower in Group 1 (Group 1 = 0% vs Group 2 = 6.5%, P = 0.033). Our study showed a high prevalence of triple-therapy antithrombotic use in LVAD patients with no significant differences in bleeding, stroke or survival. However, the risk for pump thrombosis was lower at 1-year when compared to patient receiving MAPT.

The relationship of statin therapy with recurrence of atrial fibrillation (AF) after cardioversion (CV) has been evaluated by several investigations, which provided conflicting results and particularly long-term data is scarce. We sought to examine whether upstream statin therapy is associated with long-term recurrence of AF after CV. This was a single-center registry study including consecutive AF patients (n = 454) undergoing CV. Cox regression models were performed to estimate AF recurrence comparing patients with and without statins. In addition, we performed a propensity score matched analysis with a 1:1 ratio. Statins were prescribed to 183 (40.3%) patients. After a median follow-up period of 373 (207–805) days, recurrence of AF was present in 150 (33.0%) patients. Patients receiving statins had a significantly lower rate of AF recurrence (log-rank p &lt, 0.001). In univariate analysis, statin therapy was associated with a significantly reduced rate of AF recurrence (HR 0.333 (95% CI 0.225–0.493), p = 0.001), which remained significant after adjustment (HR 0.238 (95% CI 0.151–0.375), p &lt, 0.001). After propensity score matching treatment with statins resulted in an absolute risk reduction of 27.5% for recurrent AF (21 (18.1%) vs. 53 (45.7%), p &lt, 0.001). Statin therapy was associated with a reduced risk of long-term AF recurrence after successful cardioversion.

BACKGROUND: The efficacy and safety of benralizumab, an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody, for the prevention of exacerbations in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) are not known.METHODS: In the GALATHEA and TERRANOVA trials, we enrolled patients with COPD (at a ratio of approximately 2:1 on the basis of eosinophil count [≥220 per cubic millimeter vs. RESULTS: In GALATHEA, the estimates of the annualized exacerbation rate were 1.19 per year (95% confidence interval [CI], 1.04 to 1.36) in the 30-mg benralizumab group, 1.03 per year (95% CI, 0.90 to 1.19) in the 100-mg benralizumab group, and 1.24 per year (95% CI, 1.08 to 1.42) in the placebo group; the rate ratio as compared with placebo was 0.96 for 30 mg of benralizumab (P = 0.65) and 0.83 for 100 mg of benralizumab (P = 0.05). In TERRANOVA, the estimates of the annualized exacerbation rate for 10 mg, 30 mg, and 100 mg of benralizumab and for placebo were 0.99 per year (95% CI, 0.87 to 1.13), 1.21 per year (95% CI, 1.08 to 1.37), 1.09 per year (95% CI, 0.96 to 1.23), and 1.17 per year (95% CI, 1.04 to 1.32), respectively; the corresponding rate ratios were 0.85 (P = 0.06), 1.04 (P = 0.66), and 0.93 (P = 0.40). At 56 weeks, none of the annualized COPD exacerbation rate ratios for any dose of benralizumab as compared with placebo reached significance in either trial. Types and frequencies of adverse events were similar with benralizumab and placebo.CONCLUSIONS: Add-on benralizumab was not associated with a lower annualized rate of COPD exacerbations than placebo among patients with moderate to very severe COPD, a history of frequent moderate or severe exacerbations, and blood eosinophil counts of 220 per cubic millimeter or greater (Funded by AstraZeneca [GALATHEA and TERRANOVA] and Kyowa Hakko Kirin [GALATHEA]; GALATHEA and TERRANOVA ClinicalTrials.gov numbers, NCT02138916 and NCT02155660.).

Background: Complete real-world data on the indications and outcomes of left atrial appendage closure (LAAC) outside of clinical trials are rare. In this study, we stratified patients undergoing LAAC by indication groups. Methods: This analysis of the national multicentre Austrian LAAC Registry comprised all patients that underwent LAAC up until 2018 at the currently active centres in Austria. The baseline characteristics, procedural details and outcomes between the following indication groups were compared: bleeding as an indication for LAAC (&ldquo, bleeding&rdquo, group) vs. thromboembolism despite oral anticoagulation (OAC, &ldquo, thromboembolism&rdquo, group) vs. an intolerance to OAC for reasons other than the above (&ldquo, other&rdquo, group). Results: The analysis included 186 patients, with 59.7% in the &ldquo, group, 8.1% in the &ldquo, group and 32.2% in the &ldquo, group. The CHADS2 score was the highest in the &ldquo, group and the HAS-BLED score was the highest in the &ldquo, group. The procedural outcomes were similar between groups (implantation success, 97.3%), with major complications occurring in 7.0% of patients. One-year survival free from stroke, bleeding or LAAC-associated hospitalisation was 83.9%, 90.0% and 81.4% in the &ldquo, and &ldquo, groups, respectively (p = 0.891). Conclusions: In routine clinical practice, LAAC was used in a heterogeneous patient population with atrial fibrillation (AF) and contraindication, inefficacy or intolerance to OAC. The long-term outcome was favourable in all groups.

Recent investigations of the front side metallization of high-efficiency mono-crystalline Si solar cells proved that the glass layer formed at the Si/metallization interface during the screen printing plays an essential role for the charge transport, both in n- and p-type cells. High-efficiency cells (~ 18.0% for p-type and ~ 20% for n-type cells) show similar microstructure of the glass layer and similar temperature dependence of the series resistance. From this it is concluded that the microstructure of the glass layer determines the series and contact resistance of the front side metallization. The glass layers of high-efficiency cells contain a high density of nano-Ag colloids and other precipitates which reduce the contact resistance. A percolation model was proposed and is best suited to describe the charge transport in a dirty semiconductor containing metallic precipitates. Quantitative chemical composition of the glass layer of p- and n-type cells was investigated by Energy Dispersive X-ray (EDX) microanalysis in SEM and TEM. The chemical composition of the glass layer showed (SiOx)Pb, as main constitutes and Zn, Ti, Al, Ag, P and B as minor constituents with mole fractions above the detection limit of EDX. The glass layer is therefore considered to be a dirty semiconductor rather than a perfect insulator. The mole fractions of Zn (~ 1 at%) and Al (~ 1 at%) were quantitatively analyzed. Such analyses are important to correlate microstructural features with electrical properties of the front side metallization. We could prove that in p-type cells the efficiency of the cells correlated with the chemical composition of the glass layer. In n-type cells, with Al-containing pastes EDX spectroscopy yielded Al beyond the detection limit in the glass layer, whereas for Al free pastes the Al mole fraction was below the detection limit of EDX and yielded reduced efficiencies. In p-type cells pastes with enhanced Zn mole fraction yielding zinc oxide phases in the bulk Ag finger and Zn mole fractions up to 5 at% in the glass layer.

Photoconducting thin films on the basis of PbSe have been used as functional materials for infrared detectors. The photoconducting sensor function is established by annealing PbSe films in oxygen rich and iodine rich atmospheres. Under such conditions, new, chemically more complex phases are formed that yield outstanding photoconducting properties. Such thin films are investigated after annealing, the layer structure of these films consist of a bottom layer of PbSe (1 μm) and a top layer of Pb1 Sex Iy Oz about 400 nm thick. By electron diffraction, a pseudo-orthorhombic Bravais lattice could be assigned to the quaternary phase of the top layer, responsible for photoconductivity, which was about 400 nm thick. Lattice parameters were identified as a = 0.833 nm, b = 0.662 nm and c = 1.8 nm. The grain size of the top layer was 500–700 nm and yielded single-crystal like diffraction patterns for electron diffraction. Diffraction patterns were acquired in the [100], [010] and [111] poles and could be indexed. The Bravais lattice is simple orthorhombic, no centering was found. The single-grain diffraction patterns obtained here are more valuable than the poly-crystalline diffraction patterns shown in a previous paper (part I) and yield a pseudo-orthorhombic Bravais lattice for this phase. As a consequence, the X-ray diffractograms could be indexed with the assigned Bravais lattice for this phase. The chemical composition of the new phase was measured by EDX spectroscopy in the TEM. The elemental composition of this quaternary phase was determined as Pb1 Sex Iy Oz, for the mole fraction ratio of x = Se/Pb we found 0.17 ≤ x ≤ 0.5 and for y = I/Pb we found 0.2 ≤ y ≤ 0.5. Se and I can substitute each other and therefore a solid solution is formed. The mole fraction ratio of Pb/(Se + I) was found between 1.6 and 1.9. Electron energy-loss spectra revealed a double peak structure for the volume plasmon peak, energies of the quaternary phase lay between 15.7 and 16.3 eV (peak 1) and 23.1–23.2 eV (peak 2), respectively.

Photoconductive thin films on the basis of PbSe have been used as functional materials for infrared (IR) detectors. High quality PbSe thin films were grown on glass substrates by chemical bath deposition (CBD) yielding a peak detectivity of 2.8 × 10 10 cm Hz 1/2 W −1 at room temperature. The photoconductive sensor function is established by a sensitization process by annealing PbSe films in oxygen and iodine rich atmospheres. By studying such sensitized PbSe layers we discovered that new, quaternary phases are formed at the top of the layered structure. We could show that after annealing the following layer structure had formed: a bottom layer of PbSe (1 μm) and a top layer of Pb-Se-O-I (400 nm), containing (i) a poly-crystalline and (ii) a nano-crystalline phase. The poly-crystalline phase was found to be a solid solution of Se and I and yielded an average Pb/I mole fraction ratio of 3.1 and Pb/Se of 3.9, respectively. It contained the largest iodine mole fraction of ∼20 at.% while the nano-crystalline phase yielded less iodine (

The overall efficiencies of screen printed monocrystalline Si solar cells are limited by electrical losses across the Si-metallization interface. The process of metallization affects the emitter and space charge region of the solar cell, particularly with respect to the dopant distributions. Until now, direct imaging of dopant distributions across the interface has not been reported mainly because the concentrations of dopants are far below the detection limit of conventional analytical tools. In the present study, we harness the high-resolution (100 nm) high-sensitivity chemical imaging with Nano Secondary Ion Mass Spectrometry (NanoSIMS) and correlate with microstructural and electrical properties to elucidate the factors limiting the overall cell efficiencies. We analysed two sets of p-type solar cells fabricated from identical starting materials, the only difference being the firing temperature. It was found that the overall efficiency of cells fired at 900 °C was ∼17% while the efficiency of cells fired at 960 °C was only 13.6%. In phosphorus (P) ion maps, the P emitter structure was found to be well-preserved by NanoSIMS in cells fired at 900 °C, it was completely disintegrated in the overfired cells and thereby increasing the contact resistance. The passivation layer (SiNX) was found to be disintegrated in the overfired cell and furthermore, below the metallization, a diffusion cloud was observed wherein boron (B) rich domains extend over several µm. In the overfired cell the disintegration of the SiNX layer identified in the SEM correlated with the disintegrated emitter structure (P) analysed by NanoSIMS. This implies that the disintegration of the passivation layer leads to a diffusion of the dopants resulting in the loss of overall cell efficiency. Thus, our new comprehensive approach provides unprecedented insights into the factors limiting the overall efficiencies in solar cells.

Single-crystalline, ternary n -type Bi 2 Te 3−y Se y nanowires are grown by potential-pulsed electrochemical deposition with 45 nm, 70 nm and 195 nm nominal diameters. Electrical conductivity and thermopower of the nanowires are measured. TEM analysis proves that the nanowires grow along the [110] direction with the c-axis perpendicular to the nanowire axis and yield diameters of 70–80 nm (nominally 45 nm, #1), 85–100 nm (70 nm, #2) and 265–325 nm (195 nm, #3). This yields electronic transport along the basal plane of the Bi 2 Te 3 crystal structure. Chemical composition of the nanowires is measured by TEM-EDX spectroscopy. These nanowires show exciting electronic properties, like Shubnikov-de-Haas oscillations at low temperatures, summarized in another paper. All nanowires investigated are oxygen contaminated but single crystalline, precipitates are only observed in #3 nanowire. The stoichiometry offset and fluctuations of #2 nanowire are significantly larger compared to #1 and #3 nanowires. The thermopower correlates with these structural data, the smallest thermopower is found for #2 nanowire and a similar, larger thermopower is found for #1 and #3 nanowires. For #1 and #2 nanowires dislocation densities of about 7.8 × 10 10 cm −2 and 1.0 × 10 11 cm −2 are observed, respectively, wherein dislocations lie parallel to the growth direction. While for #3 nanowire, a dislocation density of 1.2 × 10 10 cm −2 is observed and dislocations are oriented perpendicular to the growth direction. This reduces the heat conductivity of the #3 nanowire due to phonon scattering on the strain field of dislocations.

Screen printed front side contacts were investigated in n-type, high efficiency, single-crystalline Si solar cells with B doped emitters. Cells were processed identically and two different front side pastes were used: paste Ag–Al yielded efficiencies of 20.0%, and paste Ag, without Al, yielded 16.1% efficiency only. Cells contacted with paste Ag–Al yielded a continuous glass layer, a significantly higher density of Ag colloids, and an Al mole fraction of ∼1 at%. In contrast, cells contacted with paste Ag revealed a thinner but continuous glass layer as compared to cells processed with paste Ag–Al. It contained a lower density of Ag colloids and Al was below the detection limit of the EDX microanalysis. In n-type cells pyramidal shaped Ag nanocrystals did not appear, whereas for p-type cells they are formed at intersections of differently {111} oriented surface planes at the Si emitter. We did not find Ag/Al spikes at the Si emitter for cells contacted with paste Ag–Al. Cells contacted with paste Ag–Al had a smaller series resistance as well as a significantly lower specific contact resistance (4 mΩ cm2). A higher series resistance and specific contact resistance >100 mΩ cm2 was found for cells contacted with paste Ag. It was concluded that the specific contact resistance decreases with increased wetting and increased density of Ag colloids in the glass layer. The series resistance of the Ag–Al alloy contact depended only weakly on temperature, whereas the series resistance linearly increased with temperature for contacts processed with paste Ag. p- and n-type cells with maximum efficiency yield a similar microstructure of the front side contact, similar series and contact resistance, respectively. A high density of Ag colloids in the glass layer was found for cells with low specific contact resistance. This suggests that also for n-type cells a three dimensional percolative charge transport through the glass layer is assisted by the presence of metallic Ag colloids.

Resistive losses corresponding to the front-side metallization limit the efficiency of Si solar cells. At the front-side contact, the Si emitter is covered by a glass layer that is less than 1 μm thick embedded with Ag colloids to volume fraction >20%. Bulk Ag fingers are arranged on top of the glass layer. A similar microstructure is found for both n-type and p-type cells showing high efficiency. The Ag colloids constitute current filaments with reduced resistance in the glass layer, thereby introducing a percolative current which is the basis of the proposed model. This model is new and differs from the classical percolation model in its direct reliance on the macroscopic resistance of these filaments, and in considering the matrix as semiconducting rather than insulating. For periodically arranged Ag colloids of fixed diameter, the percolative limit of 13% in two dimensions (2D) and 15% in three dimensions (3D) depends only on the volume fraction of colloids but not their size. The resistance of randomly arranged and sized Ag colloids confirms the analytical results. The model explains quantitatively, consistent with microstructural analyses, why low contact resistances are found in solar cells with high colloid density. The introduced percolation model is also relevant for other systems in which metallic precipitates are found in a semiconducting matrix.

Extraction of data from the electronic medical record is becoming increasingly important for quality improvement initiatives such as the American Society of Anesthesiologists Perioperative Surgical Home. To meet this need, the authors have built a robust and scalable data mart based on their implementation of EPIC containing data from across the perioperative period. The data mart is structured in such a way so as to first simplify the overall EPIC reporting structure into a series of Base Tables and then create several Reporting Schemas each around a specific concept (operating room cases, obstetrics, hospital admission, etc.), which contain all of the data required for reporting on various metrics. This structure allows centralized definitions with simplified reporting by a large number of individuals who access only the Reporting Schemas. In creating the database, the authors were able to significantly reduce the number of required table identifiers from >10 to 3, as well as to correct errors in linkages affecting up to 18.4% of cases. In addition, the data mart greatly simplified the code required to extract data, making the data accessible to individuals who lacked a strong coding background. Overall, this infrastructure represents a scalable way to successfully report on perioperative EPIC data while standardizing the definitions and improving access for end users.

Screen printed front side contacts were investigated in single-crystalline (planar and textured) Si solar cells with n-type emitters, yielding maximum efficiencies of 18.0%. The crystallographic orientation of the Si surface and the paste strongly affect the contact formation as well as the contact resistance of the cells. For textured cells a continuous glass layer together with the formation of Ag colloids yielded a small contact resistance. Planar 〈111〉oriented Si yielded specifically lower contact resistance (〈5 mΩ cm 2 ) as compared to planar 〈100〉 orientation (〉10–40 mΩ cm 2 ) for different pastes. Pyramidal Ag crystals are formed only on 〈100〉 oriented Si, whereas lens shaped Ag crystals are grown on 〈111〉surfaces. From this it was concluded that the shape of the Ag nanocrystals determines the contact resistance, pyramidal Ag crystals formed on 〈100〉 planar surfaces yielded cells with large contact resistance and are, therefore, not considered to be necessary for a low contact resistance. Temperature dependent series resistance measurements yielded metallic behavior for cells with the lowest contact resistance bound to a certain paste. For other pastes and processing conditions a semiconducting behavior of the series resistance was found. However, cells with significant density of colloids in the glass layer yielded a small series and contact resistance. By considering the above arguments, a percolation model has been introduced in which metallic Ag colloids generate current filaments across the glass layer. This reduces the resistivity of the glass layer and thereby introduces a percolative nature of the current via Ag nanocolloids. The percolation limit for the 2d case was calculated for periodically arranged colloids with equal size and yields a minimum volume fraction of 15% for the Ag colloids in the glass layer.

Introduction Patients with durable left ventricular assist devices (LVADs) are at high risk for serious infection and associated mortality. Furthermore, these patients also have a high prevalence of iron deficiency due to ongoing hemolysis, increased propensity for gastrointestinal bleeding, and dysregulated iron metabolism that accompanies mechanical circulatory support and heart failure. Intravenous (IV) iron-related supplementation [IVIRS, including IV iron infusion or red blood cell transfusion (RBC)] has been hypothesized to increase risk of infection. Hypothesis IVIRS (IV iron infusion or RBC transfusion) is associated with an increased risk of serious infection in LVAD patients. Methods This is a single center, retrospective, observational cohort study of 211 consecutive adult patients [median age 57.2 years (25th-75th percentile: 48.7-65.7 years), 19% female] who were discharged and followed after de-novo LVAD implantation between May 2008 and December 2019. Patients were followed until either end of the study period, or occurrence of death, heart transplantation, or LVAD removal/replacement, whichever came first. All administration of IVIRS and diagnosis of serious infection after discharge from index hospitalization was abstracted from the electronic medical record. Serious infection was defined as the first incident infection requiring hospitalization, divided into LVAD-associated infections (pump/cannula, pocket or driveline infection) and non-LVAD infections. Multivariate logistic regression was used to examine the association between IVIRS and serious infections. Results Over a median follow-up of 15.2 months (25th-75th percentile: 6.9-29.4 months), 69 (33%) LVAD patients received IVIRS, of whom 47 (68%) received IV iron and 44 (64%) received RBC transfusion. During follow-up, 87 (41%) patients suffered a serious infection, of which 48 (55%) were LVAD-associated infections and 39 (45%) were non-LVAD infections. After adjustment for age, sex, diabetes, chronic kidney disease, prior cardiac surgery, destination therapy and pre-IVIRS serious infection, LVAD patients who received IVIRS had 2.85 times higher odds of any first serious infection compared to those who did not receive IVIRS during the study period (95% CI 1.49-5.46, p=0.002). Patients who received IVIRS had a significant 3.03 times greater odds of non-LVAD infection (95% CI 1.37-6.70, p=0.006) and a non-significant 1.54 times greater odds of LVAD infection (95% CI 0.75-3.18, p=0.24), compared to LVAD patients who did not receive IVIRS. Conclusion IVIRS use is associated with a higher risk of serious infection in LVAD patients, primarily due to serious non-LVAD infections. These findings merit further study in larger cohorts and randomized trials to determine best practices surrounding IVIRS in LVAD patients.

Background: All usual daily doses of plain aspirin inhibit thromboxane B2 (TXB2) as well as prostaglandin E2 (PGE2). The role of 81-mg enteric-coated aspirin (ECA) is controversial. Method: In a randomized, double-blind trial, 37 patients (25 men and 12 women) with chronic stable coronary disease taking ECA 81 mg at baseline were assigned to plain aspirin 81, 162.5, 325, 650 or 1300 mg daily for 12 weeks. At baseline and 12 weeks, blood was tested for TXB2 and PGE2. Results: All doses of plain aspirin produced virtually identical reductions in TXB2 and PGE2. For all doses combined, the mean ratio of the 12-week to baseline value was 0.03 for TXB2 (p < 0.001) and 0.63 for PGE2 (p < 0.001). Conclusion: These data indicate that ECA 81 mg daily does not inhibit TXB2 and PGE2, markers of acute and systemic responses to aspirin. Randomized trials designed a priori to test this hypothesis are necessary.

The objective of the present study was to evaluate the combined effect of vegetation and N deposition on microbial community composition in forest soils. For this, microbial biomass and community structure were assessed by ester linked fatty acid methyl ester (EL-FAME) analyses for 12 European forest sites representing different forest types (coniferous/deciduous) and differing in annual N loads (2–40 kg N ha−1). Microbial community composition was affected by vegetation as indicated by a higher proportion of the marker for arbuscular mycorrhiza (AM) fungi—16:1 11ω—in deciduous forest soils (1.2%–5.7% of total EL-FAMEs) compared to acidic coniferous forest soils (0.5%–1.6%). The two pine forest sites investigated showed the highest proportion of fungi (up to 28% of total EL-FAMEs) and the lowest proportions of Gram-negative and Gram-positive bacteria of all study sites. Nitrogen deposition rates were highly correlated with the ratios of cyclopropyl fatty acids to their precursors (r = 0.82; P 30 kg N ha−1a−1).

Nitrifier denitrification (i.e. nitrite reduction by ammonia oxidizers) is one of the biochemical pathways of nitrous oxide (N2O) production. It is increasingly suggested that this pathway may contribute substantially to N2O production in soil, the major source of this greenhouse gas. However, although monoculture studies recognize its potential, methodological drawbacks prohibit conclusive proof that nitrifier denitrification occurs in actual soils. Here we suggest and apply a new isotopic approach to identify its presence in soil. In incubation experiments with 12 soils, N2O production was studied using oxygen (O) and nitrogen (N) isotope tracing, accounting for O exchange. Microbial biomass C and N and phospholipid fatty acid (PLFA) patterns were analysed to explain potential differences in N2O production pathways. We found that in at least five of the soils nitrifier denitrification must have contributed to N2O production. Moreover, it may even have been responsible for all NH4+-derived N2O in most soils. In contrast, N2O as a by-product of ammonia oxidation contributed very little to total production. Microbial biomass C and N and PLFA-distinguished microbial community composition were not indicative of differences in N2O production pathways. Overall, we show that combined O and N isotope tracing may still provide a powerful tool to understand N2O production pathways, provided that O exchange is accounted for. We conclude that nitrifier denitrification can indeed occur in soils, and may in fact be responsible for the greater proportion of total nitrifier-induced N2O production.

Kurzfassung Die Technologie räumlicher elektronischer Schaltungsträger (Molded Interconnect Devices – MID) bietet mit der hohen Gestaltungsfreiheit, Umweltverträglichkeit sowie dem umfangreichen Rationalisierungspotenzial vielfältige Möglichkeiten zur Realisierung innovativer Produkte und effizienter Produktionsprozesse. Charakteristisch ist die direkte stoffliche Integration von Mechanik und Elektronik auf einem Bauteil. Die Umsetzung innovativer Produktideen erfordert umfangreiches Entwicklungs-Know-how und die entsprechende Rechnerunterstützung. Dabei genügt der Einsatz klassischer Konstruktionssoftware für Mechanik und Schaltungsentwurf nicht den Anforderungen von MID. Neben einer dreidimensionalen Entwicklungsumgebung für die Darstellung des räumlichen Schaltungsträgers ist die Integration von Konstruktionsbefehlen aus verschiedenen domänenspezifischen Software-Paketen notwendig. Bereits in der frühen Konstruktionsphase müssen die spezifischen Eigenschaften der MID-Technologie während des Fertigungsprozesses berücksichtigt werden. Da MID keine Standardlösungen wie elektronische Baugruppen in planarer Leiterplattentechnik sind, kommt der Kenntnis aller Prozessschritte (elektronisches und mechanisches Design, Werkstoffauswahl, Spritzguss, Metallisierung und AVT) hohe Bedeutung zu.

Studies on the combined effects of beech–spruce mixtures are very rare. Hence, forest nutrition (soil, foliage) and nutrient fluxes via throughfall and soil solution were measured in adjacent stands of pure spruce, mixed spruce–beech and pure beech on three nutrient rich sites (Flysch) and three nutrient poor sites (Molasse) over a 2-year period. At low deposition rates (highest throughfall fluxes: 17 kg N ha −1 year −1 and 5 kg S ha −1 year −1 ) there was hardly any linkage between nutrient inputs and outputs. Element outputs were rather driven by internal N (mineralization, nitrification) and S (net mineralization of organic S compounds, desorption of historically deposited S) sources. Nitrate and sulfate seepage losses of spruce–beech mixtures were higher than expected from the corresponding single-species stands due to an unfavorable combination of spruce-similar soil solution concentrations coupled with beech-similar water fluxes on Flysch, while most processes on Molasse showed linear responses. Our data show that nutrient leaching through the soil is not simply a “wash through” but is mediated by a complex set of reactions within the plant–soil system.

The soil microbial communities of a landfill cover substrate, which was treated with landfill gas (100 l CH4 m−2 d−1) and landfill leachate for 1.5 years, were investigated by phospholipid fatty acid (PLFA), ergosterol and respiratory quinone analyses. The natural 13C depletion of methane was used to assess the activity of methanotrophs and carbon turnover in the soil system. Under methane addition, the soil microbial community was dominated by PLFAs (14:0 and 16:1 isomers) and quinones (ubiquinone-8 and 18-methylene-ubiquinone-8) related to type I methanotrophs, and 18:1 PLFAs contained in type II methanotrophs. While type I methanotrophic PLFAs were 13C depleted, i.e. type I methanotrophs were actively oxidising and assimilating methane, 13C depletion of 18:1 PLFAs was low and inconsistent with their abundance. This, possibly reflects isotopic discrimination, assimilation of carbon derived from type I methanotrophs and a high contribution of non-methanotrophic bacteria to the 18:1 isomers. Landfill leachate irrigation caused the methanotrophic community to shift closer to the soil surface. It also decreased 18:1 PLFAs, while type I methanotrophs were probably stimulated. Gram positive bacteria, but not fungi, were also 13C depleted and consequently involved in the secondary turnover of carbon originating from methanotrophic bacteria. Cy17:0 PLFA was 13C depleted in deep soil layers, indicating anaerobic methane oxidation.

Microbial biomass, respiratory activity, and in-situ substrate decomposition were studied in soils from humid temperate forest ecosystems in SW Germany. The sites cover a wide range of abiotic soil and climatic properties. Microbial biomass and respiration were related to both soil dry mass in individual horizons and to the soil volume in the top 25cm. Soil microbial properties covered the following ranges: soil microbial biomass: 20 μg C g -1 -8.3 mg C g -1 and 14-249 g C m -2 , respectively; microbial C-to-total organic C ratio: 0.1%-3.6%; soil respiration: 109-963 mg CO 2 -C m -2 h -1 ; metabolic quotient (qCO 2 ): 1.4-14.7 mg C (g C mic ) -1 h-1; daily in-situ substrate decomposition rate: 0.17%-2.3%. The main abiotic properties affecting concentrations of microbial biomass differed between forest-floor/organic horizons and mineral horizons. Whereas microbial biomass decreased with increasing soil moisture and altitude in the forest-floor/ organic horizons, it increased with increasing N tot content and pH value in the mineral horizons. Quantities of microbial biomass in forest soils appear to be mainly controlled by the quality of the soil organic matter (SOM), i.e., by its C: N ratio, the quantity of N tot , the soil pH, and also showed an optimum relationship with increasing soil moisture conditions. The ratio of C mic to C org was a good indicator of SOM quality. The quality of the SOM (C: N ratio) and soil pH appear to be crucial for the incorporation of C into microbial tissue. The data and functional relations between microbial and abiotic variables from this study provide the basis for a valuation scheme for the function of soils to serve as a habitat for microorganisms.

Purpose: The goal of this study was to identify and validate novel serum markers of human colorectal cancer as potential candidates for noninvasive detection of early colorectal neoplasm.Experimental Design: Employing two-dimensional gel electrophoresis and mass spectrometry, we analyzed 16 matched colorectal cancer and adjacent normal tissue samples. Proteins found to be elevated in cancer tissue were further validated by generating antibodies which were used for immunoblotting of tissue samples and for the development of highly sensitive immunoassays for assessment of serum samples.Results: In total, 735 different proteins were identified in colon tissue. Strong elevation in colorectal cancer for five proteins was confirmed by immunoblot analysis: transforming growth factor-β induced protein ig-h3 (βIG-H3), nicotinamide N-methyltransferase (NNMT), nucleoside diphosphate kinase A (nm23-H1), purine nucleoside phosphorylase (PNPH), and mannose-6-phosphate receptor binding protein 1 (M6P1). Elevated levels of NNMT, which is not predicted to be secreted but is known as a cytoplasmic protein, were found in serum from patients with colorectal cancer. Employing a receiver-operating characteristic curve based on the measurement of 109 patients with colorectal cancer and 317 healthy controls, we obtained an area under the curve of 0.84 for NNMT, which was superior to the established tumor marker carcinoembryogenic antigen with an area under the curve of 0.78.Conclusions: It is proposed that NNMT serum levels may have significance in the early detection and in the management of patients with colorectal cancer.

Phosphonates are widely used as chelating agents, e.g., in water cooling systems, in bleaching baths or as scale inhibitors in deflocculation agents. They are considered to be difficult to degrade and produce aminomethylphosphonic acid (AMPA) as a metabolite. As the fate of phosphonates in the environment is not very well known the present work aims at simulating the time dependent photodegradation of four selected phosphonates: nitrilotris-methylenephosphonic acid (NTMP), ethylenediamine-tetra-methylenephosphonic acid (EDTMP), diethylenetriaminepenta-methylenephosphonic acid (DTPMP) and hexaethylenediamine-tetra-methylenephosphonic acid (HDTMP), at concentrations of 1 mg/l (i.e. 3.2 microM NTMP, 2.3 microM EDTMP, 1.7 microM DTPMP and 2.0 microM HDTMP) irradiated by a middle pressure mercury lamp emitting between 190 and 600 nm. The influence of iron under different pH ranges (3, 5-6 and 10) are tested. The degradation of phosphonates is measured by the release of orthophosphates (PO4-P) and aminomethylphosphonic acid (AMPA). This study shows that phosphonates are substances that undergo UV light conversion, which is enhanced in the presence of iron. The half-life without iron is between 15 and 35 min at pH 3, between 10 and 35 min at pH 5-6 and between 50 and 75 min at pH 10. The half-life in the presence of 3.6 microM iron is between 5 and 10 min at pH 3, between 5 and 15 min at pH 5-6 and between 35 and 60 min at pH 10. The individual substances do not significantly influence the reaction rates whereas the presence of iron and the pH have significant effects. The total conversion of phosphonates after 90 min is 75-100% for pH values of 3 and 5-6 and 55-75% for a pH of 10 dependent on the presence of iron. In the environment longer degradation times are to be expected since natural light is weaker by a factor between 125 and 300 in the UVB, a factor between 3 and 8 in the UVA and of the same intensity in the visible range than the light in our study. Although orthophosphates are the major products, AMPA is also shown to be a by-product of the photodegradation of phosphonates that is later converted into orthophosphate.

Phospholipid fatty acid (PLFA) patterns were used to describe the composition of the soil microbial communities under 12 natural forest stands including oak and beech, spruce–fir–beech, floodplain and pine forests. In addition to the quantification of total PLFAs, soil microbial biomass was measured by substrate-induced respiration and chloroform fumigation–extraction. The forest stands possess natural vegetation, representing an expression of the natural site factors, and we hypothesised that each forest type would support a specific soil microbial community. Principal component analysis (PCA) of PLFA patterns revealed that the microbial communities were compositionally distinct in the floodplain and pine forests, comprising azonal forest types, and were more similar in the oak, beech and spruce–fir–beech forests, which represent the zonal vegetation types of the region. In the nutrient-rich floodplain forests, the fatty acids 16:1u5, 17:0cy, a15:0 and a17:0 were the most prevalent and soil pH seemed to be responsible for the discrimination of the soil microbial communities against those of the zonal forest types. The pine forest soils were set apart from the other forest soils by a higher abundance of PLFA 18:2u6,9, which is typical of fungi and may also indicate ectomycorrhizal fungi associated with pine trees, and high amounts of PLFA 10Me18:0, which is common in actinomycetes. These findings suggest that the occurrence of azonal forest types at sites with specific soil conditions is accompanied by the development of specific soil microbial communities. The study provides information on the microbial communities in undisturbed forest soils which may facilitate interpretation of data derived from managed or even damaged or degraded forests. q 2004 Elsevier Ltd. All rights reserved.

Mesophase pitch, in common with other liquid crystalline substances, exhibits preferred angles of molecular orientation at its boundaries with other phases. These orientations, or surface anchoring states, are important because they influence the ultimate graphene layer arrangement in a variety of carbon materials where the pitch precursor encounters a composite filler, a free surface, a bubble cavity, or the surfaces of processing equipment such as a fiber spinneret. This paper presents experimentally determined anchoring states for two mesophase pitches at free surfaces, and on twenty solid substrates. Edge-on anchoring is found to be the most common state, occurring on the free surface, on some metals, on PTFE, and on all oxides with the exception of the lamellar material mica. The optical texture associated with the edge-on films is observed to be stable during carbonization up to 1200 °C. Face-on anchoring is observed on carbon graphene planes, mica and the metals Pt, Ni, and Ag. Trends in the data are discussed in terms of the strength of pitch/substrate intermolecular forces relative to π–π bonding between large discotic mesogens within the pitch. The implications for the structure and properties of carbon materials are discussed.

Different methods of tillage are investigated in a field trial in Austria. In those variants where soils are treated with a cultivator respectively a plough in autumn the contents of mineral N (Nmin) in 0-90cm soil depth increased significantly. Therefore the danger of N-leaching or N-losses in autumn or winter is higher in intensively tilled soils (without plant cover) than in soils with minimum tillage (treatment only with rotary driller without any primary treatment before seeding). In this variant Nmin-contents are lower even at the beginning of vegetation due to the plant cover and reduced tillage. At this time the potential of N mineralisation is higher in the minimum tilled plots compared to the more intensively tilled soils due to the accumulation of organic matter. However, despite enhanced potential N availability the N contents of the crops did not increase. The yields don't differ in the investigated tillage systems and N balances are the highest under minimum tillage, therefore a higher N fer...