Total AE Research Articles

Safety, Tolerability, and Pharmacokinetics of NIM-1324 an Oral LANCL2 Agonist in a Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Trial.

NIM-1324 is an oral investigational new drug for autoimmune disease that targets the Lanthionine Synthetase C-like 2 (LANCL2) pathway. Through activation of LANCL2, NIM-1324 modulates CD4+ T cells to bias signaling and cellular metabolism toward increased immunoregulatory function while providing similar support to phagocytes. In primary human immune cells, NIM-1324 reduces type I interferon and inflammatory cytokine (IL-6, IL-8) production. Oral NIM-1324 was assessed for safety, tolerability and PK in normal healthy volunteers in a randomized, double-blind, placebo-controlled trial. Subjects (n = 57) were randomized into five single ascending dose (SAD) cohorts (250, 500, 750, 1000, 1500 mg, p.o.) and three multiple ascending dose (MAD) cohorts (250, 750, 1500 mg QD for 7 days, p.o.). NIM-1324 did not increase total AE rates in individual cohorts or pooled active groups in SAD or MAD with no SAEs in the study. Oral NIM-1324 dosing does not result in any clinically significant findings by biochemistry, coagulation, ECG, hematology, or urinalysis when compared to placebo. Plasma exposure, as measured by area under the curve from 0 to 24 h (AUC0-24), scaled dose proportionally over 250-1000 mg. At 250 mg, NIM-1324 successfully engaged the target with an upregulation of Lancl2 and key transcriptional biomarkers in whole blood. In conclusion, NIM-1324 treatment is well-tolerated up to daily oral doses of at least 1500 mg (nominal), a ≥ six-fold margin over the anticipated therapeutic dose, and 1000 mg (maximum observed exposure), at least a four-fold margin over the anticipated therapeutic dose with no dose limiting toxicities.

Blood-Feeding Patterns and Resting Behavior of Aedes aegypti from Three Health Districts of Ouagadougou City, Burkina Faso.

Recent dengue outbreaks have occurred in Ouagadougou and Bobo-Dioulasso, the two major cities of Burkina Faso. Dengue is a viral disease transmitted primarily by Aedes aegypti, a highly anthropophilic mosquito that thrives in human-transformed environments and breeds predominantly in artificial containers. In 2018, we investigated the resting and blood-feeding habits of Ae. aegypti in urban settings of Ouagadougou. In a 3-month cross-sectional study starting in August 2018, indoors and outdoors resting adult mosquitoes were collected using Prokopack aspirators in three health districts (HD). All mosquitoes were morphologically identified, and DNA was extracted from blood-fed Ae. aegypti females. A multiplex polymerase chain reaction with specific primers was used to identify the origin of the blood meal. A total of 4,256 adult Ae. aegypti mosquitoes, including 1,908 females, were collected. A preference for exophily was recorded in Bogodogo and Nongremassom, although an unexpectedly higher proportion of blood-fed females were found indoors than outdoors. Respectively, 96.09%, 91.03%, and 95.54% of the blood meals successfully analyzed in Baskuy, Bogodogo, and Nongremassom were from a single human host, with the remainder from domestic mammals as single or multiple hosts. Modeling total Ae. aegypti and blood-fed female counts showed that among other predictors, human density, outdoor environment, and house type affect their total densities. Our study revealed an exophilic tendency as well as a pronounced anthropophilic preference of Ae. aegypti adults, critical findings to consider when planning accurate entomological surveillance and effective interventions against Ae. aegypti in urban settings.

Comparison of Aedes aegypti arbovirus transmission thresholds in two communities with differing water supply infrastructure

BackgroundTo assess whether the ‘economic boom’ in the tropical seaport city of Barranquilla improved tapped water supplies to socio-economically poor neighbourhoods resulting in: (1) their reduced use for domestic water-storage in large (> 1,000-litre) custom-made cement tanks which are their principal Aedes aegypti breeding sites and (2) their pupae/person index (PPI) values to below their established 0.5–1.5 PPI arbovirus transmission-threshold value, compared to matched neighbourhoods in the: (a) pre-economic boom (2004) period in Barranquilla and (b) economically-neglected seaport city of Buenaventura.MethodsThe simple, accurate and robust water surface sweep-net/calibration factor or total count methods were used to determine the total Ae. aegypti pupae numbers in greater or less than 20-litre water-holding container types located ‘inside’ or ‘outside’ these neighbourhood premises. The women residents also participated in questionnaire-based responses about their domestic water supplies, water-storage and maintenance and mosquito life stages and disease transmission knowledge, to subsequently plan appropriate resident education programmes. Microsoft Excel 8.0 with OpenEpi was used to determine the samples sizes and the statistical values.ResultsTapped water supplies to the three poor Barranquilla neighbourhoods were dramatically increased from 2004 to 2023 resulting in their residents significantly reducing their: (a) large cement water-storage tanks from 1 per 6.9 (2004) to 1 per 31.2 (2020) premises (z = 10.5: p = 0) and (b) PPI values to 0.16, 0.19 and 0.53 (mean: 0.29: 95% CI ± 0.4) in each study neighbourhood. In contrast, tapped water supplies remained inadequate in the Buenaventura neighborhoods, thereby resulting in their continued use of many large (> 1,000-litre) water-storage containers (Barranquilla: 1 per 31.2 and Buenaventura: 1 per 1.5 premises: z = − 9.26: p = 0), with unacceptably high 0.81, 0.88 and 0.99 PPI values in each study neighbourhood (mean 0.89: 95% CI ± 0.12).ConclusionsImproved tapped water supplies resulted in reduced numbers of large custom-made stoneware water-containers, as are employed by poor residents throughout the world, as well as their Ae. aegypti PPI transmission threshold values which, together with appropriate residents’ education programmes, are also urgently to reduce to prevent/reduce Ae. aegypti transmitted human diseases globally.

Evaluation of efficacy and safety of the AHPL/AYCAP/0114 capsule in subjects suffering from erectile dysfunction

Abstract Background and Objectives: Oral phosphodiesterase type 5 (PDE5) inhibitors facilitate erections, however, unable to restore sexual desire (SD), overcome sexual resistance, or treat relational discord. The current investigation aimed to assess the safety and effectiveness of the AHPL/AYCAP/0114 capsule in subjects experiencing erectile dysfunction (ED). Materials and Methods: The study design employed a noncomparative, interventional, open-label format. It was conducted at a single center and followed a prospective clinical methodology. A total of 46 patients completed the study. Patients were asked to take two AHPL/AYCAP/0114 capsules two times a day orally after meals with milk for 90 days. Changes in all domain scores of the International Index of Erectile Function questionnaire, hardness of penis, male sexual health, sexual encounter profile, overall improvement, serum total testosterone, AE, and lab parameters were outcomes of the study. Statistical analysis involved the application of the chi-square test, Wilcoxon signed-rank test, and Student t test to examine the relevant data. Results: On day 90, there was a notable and statistically significant increase in the mean Erectile Function Domain Score, with a rise of 42.4%. Significant improvements were observed on day 90 across multiple domains, including mean orgasmic function, mean SD, mean intercourse satisfaction, and mean sexual satisfaction domain scores. On day 90, complete improvement with full penile rigidity was observed in 78.3% of subjects, whereas 67.4% of subjects were very satisfied with the treatment and their sexual health and 78% of subjects showed good to excellent improvement. Serum total testosterone increased significantly by 1.29 times. Following the treatment, there were no significant changes observed in any of the laboratory parameters, indicating the safety of the AHPL/AYCAP/0114 capsule. Interpretation and Conclusions: The AHPL/AYCAP/0114 capsule was found to be safe and effective for the treatment of ED.

Identification of bird cherry‐oat aphid and greenbug resistance sources from Aegilops tauschii for wheat improvement

AbstractBird cherry‐oat aphid (BCOA) and greenbug pose a persistent threat to wheat production in many wheat‐growing regions. Currently, greenbug resistance genes are limited for wheat improvement, and BCOA resistance sources are even more scarce. Thus, it is urgent to identify BCOA and greenbug resistance sources in wheat gene pools. An Aegilops tauschii (Ae. tauschii) panel of 260 accessions, which accounted for 48% of the total Ae. tauschii accessions available in global germplasm banks, was evaluated for BCOA resistance, and a set of BCOA‐resistant lines were identified. The same panel was evaluated for response to greenbug biotypes C, E, F, G, I, and TX1. A total of 102 lines exhibited 14 unique resistance profiles or phenotypes featuring resistance to at least one biotype. The frequency of resistant lines varied among lineages or subspecies, from 62% in Lineage 1 (subspecies tauschii) to 18% in Lineage 2 (subspecies stangulata), indicating conservation of genetic variance for greenbug resistance was nonrandom. Ae. tauschii accessions resistant to both BCOA and greenbug were identified for enhancing aphid resistance.

Comparison of aerosol optical properties over Lumbini, Pokhara and Langtang-Base Camp


 
 
 
 The comparative study of aerosol optical properties at different tourist places in Nepal has been performed. Lumbini, Pokhara and Langtang-Base Camp (BC) were the places chosen for observation. Aerosols are made up of a variety of airborne particles both fine and coarse and are most prevalent in urban industrial Areas. The data was collected from AERONET websites between 2017 and 2019 for each of the locations. The ranges of AOD over Pokhara and Langtang-BC were discovered to be lower (0.1 and 0.01) and the maximum and minimum values of AOD (675 nm) in Lumbini occurred predominantly in winter and summer monsoon respectively. The causes of the highest AOD levels were land clearing for crop cultivation and vegetation fires which were then followed by biomass burning for heating purposes and pollution from brick kilns, industry and vehicles. AOD, angstrom exponent (α and β) and Visibility are distinct from typical seasonal variations. The total AE fluctuations show that a combination of fine and coarse mode particles as well as anthropogenic aerosols made up the majority of the aerosol loading during the research period. Visibility was inversely related to the turbidity coefficient (β). Three times as much visibility was discovered over Langtang-BC as compared to Lumbini and Pokhara. Over these three locations, precipitable water peaked in the summer and dropped in the winter. These three sites seasonal changes are found to be distinct for each parameter.
 
 
 

Present and future cost of alkaline and PEM electrolyser stacks

We use complementary bottom-up and top-down approaches to assess the current cost of AE and PEM stacks and how the costs are expected to come down by 2030. The total AE and PEM stack cost reduce from a range of 242–388 €/kW and 384–1071 €/kW in 2020 to 52–79 €/kW and 63–234 €/kW in 2030 respectively. The main drivers of these cost reductions are an increased current density and a reduction and/or replacement of expensive materials with cheaper alternatives. To a lesser extent, manufacturing and labor costs reduction is expected due to mass manufacturing at a GW scale. The total cost decrease is less prominent for AE than PEM due to AE's maturity. The uncertainty range for PEM stacks is due to the low TRL associated with the advanced design PEM stack.

Mechanical properties and acoustic emission analysis of desert sand concrete reinforced with steel fiber

In this study, to reduce the consumption of natural sand and improve the utilization rate of desert sand in western China, while preparing 14 groups of samples, desert sand is used to replace natural sand by the ratio of 20%, 40%, and 60%, and steel fiber is mixed with volume fraction 0.5%, 1.0%, 1.5%, and 2.0%. The mechanical properties of the specimens, including compressive strength, splitting tensile strength, and axial compressive strength were tested. Besides, the microstructures of the samples were analyzed by SEM, XRD, and acoustic emission detection technologies to identify the damage process. The results show that the desert sand can refine the microstructure and fill the pores, and it has good comprehensive properties at a 40% substitution rate. The compression properties of specimens are not apparently improved, but the tensile strength and deformation properties are significantly improved. The steel fiber with 1.5 vol% content behaves better, and the 28d compressive strength of the optimized group reaches 58.7 MPa. As a result, the polynomial fitting degree of total AE hits and stress level receives a more incredible goodness (R2) value than 0.96. The strength characteristics of steel fiber-desert sand concrete (SFDSC) can meet the demands of C40 concrete, and this research can provide a reference for engineers using desert sand in their designs.

Water with larvae: Hydrological fertility, inequality, and mosquito urbanism

Aedes aegypti, the primary vector for dengue, chikungunya and zika, breeds mainly in stored/stagnant water and thrives in contexts of rapid urbanization in tropical countries. Some have warned that climate change, in conjunction with urbanization, could drive the proliferation of Aedes aegypti mosquitoes. In Colombia dengue has been endemic since the 1990s and the country had the highest number of cases of zika virus in the world after Brazil. Studies have found that domestic stored water contributes to high percentages of the total Ae. aegypti pupal population in Colombian urban sectors. In particular, neighborhoods where water service provision is intermittent are vulnerable to mosquito-borne diseases as water is stored inside households. This article draws on archival work, interviews, and entomological literature to reflect on the ways in which rapid urbanization in the context of armed conflict, infrastructural inequality, the absence of formal jobs, and specific water laws and regulations produce water and Aedes aegypti in the city. It offers an initial attempt to theorize water with larvae by focusing on two interrelated processes. First, the historical and geographic processes that underlie the production of stored water, which despite being treated can become a place of fertility where mosquitoes can flourish. Secondly, the processes by which water, mosquitoes, pathogens, and human bodies become interrelated. This entails thinking about some homes in Barranquilla as socioecological assemblages that are dynamically produced, socially and materially.

Numerical simulation to study the effect of spectral division of solar irradiance on the spectral splitting photovoltaic/thermal system

As a typical photo-thermal-electric multiphysics process, the energy transfer and conversion in spectral splitting photovoltaic/thermal (PV/T) systems are rather complex. For a better prediction of the system performance, a fully-coupled finite volume-discrete ordinates (FV-DO) radiation model for the numerical simulation of the PV/T system was developed. However, the previously proposed models still lacked detailed discussion for the spectrum division, to improve the criteria for the “spectrum mesh”, this study applied the wavelet decomposition method and the piecewise constant fitting method for the spectrum division in the fully-coupled model and herein evaluated the initially introduced spectrum errors (the total radiation absolute error AE, root mean square error RMSE, and the correlation coefficient γ). Then the influence of spectrum division on the PV/T system performances (the absorbed radiation, PV cell temperature, energy efficiency, and merit function) were comprehensively investigated. Eventually, the relations between initially introduced spectrum indexes and the absolute errors of performance indicators comparing with benchmark results were discussed. The result of 20 bands divided by the piecewise constant fitting method, which could achieve relative errors of PV temperature, energy efficiency from the benchmark by 0.046% and 0.840%, respectively, was recommended as a compromise between the accuracy and the increasing computing resources. RSME and γ of the discrete spectrum can be used to initially estimate the accuracy of the performance of the spectral splitting PV/T system.

The entomological impact of passive metofluthrin emanators against indoor Aedes aegypti: A randomized field trial.

BackgroundIn the absence of vaccines or drugs, insecticides are the mainstay of Aedes-borne disease control. Their utility is challenged by the slow deployment of resources, poor community compliance and inadequate household coverage. Novel application methods are required.Methodology and principal findingsA 10% w/w metofluthrin “emanator” that passively disseminates insecticide from an impregnated net was evaluated in a randomized trial of 200 houses in Mexico. The devices were introduced at a rate of 1 per room and replaced at 3-week intervals. During each of 7 consecutive deployment cycles, indoor resting mosquitoes were sampled using aspirator collections. Assessments of mosquito landing behaviours were made in a subset of houses. Pre-treatment, there were no differences in Aedes aegypti indices between houses recruited to the control and treatment arms. Immediately after metofluthrin deployment, the entomological indices between the trial arms diverged. Averaged across the trial, there were significant reductions in Abundance Rate Ratios for total Ae. aegypti, female abundance and females that contained blood meals (2.5, 2.4 and 2.3-times fewer mosquitoes respectively; P<0.001). Average efficacy was 60.2% for total adults, 58.3% for females, and 57.2% for blood-fed females. The emanators also reduced mosquito landings by 90% from 12.5 to 1.2 per 10-minute sampling period (P<0.05). Homozygous forms of the pyrethroid resistant kdr alleles V410L, V1016L and F1534C were common in the target mosquito population; found in 39%, 24% and 95% of mosquitoes collected during the trial.Conclusions/SignificanceThis is the first randomized control trial to evaluate the entomological impact of any volatile pyrethroid on urban Ae. aegypti. It demonstrates that volatile pyrethroids can have a sustained impact on Ae. aegypti population densities and human-vector contact indoors. These effects occur despite the presence of pyrethroid-resistant alleles in the target population. Formulations like these may have considerable utility for public health vector control responses.

Comparative quantitative safety profiles of PD-1 and PD-L1 checkpoint inhibitor monotherapies: A Bayesian model-based meta-analysis.

e15167 Background: Anti-cancer therapies with immune checkpoint inhibitors (ICIs) are associated with immune-mediated adverse events (imAEs). The objective of this study was to use a Bayesian model-based meta-analysis, to compare safety profiles of PD-1 and PD-L1 checkpoint inhibitor monotherapies. Methods: We performed an exhaustive search through PubMed and TrialTrove databases, ASCO and ESMO abstracts to identify relevant ICI safety data. A Bayesian meta-analysis (BMA) was performed for all-grade and high-grade (Grades 3-4) treatment-related AEs (trAEs) and immune-mediated AEs (imAEs). The analysis was performed for total AEs and individual AEs affecting different organs: dermatological (rash, pruritus), gastrointestinal (diarrhea, colitis), hepatic (AST, ALT), respiratory (pneumonitis), and endocrine (hyperthyroidism, hypothyroidism). Software STAN along with the brms package in R software were used for the BMA. Results: A total of 145 articles were identified, covering 30,737 patients in 153 cohorts treated with anti PD-1 and anti PD-L1 monotherapies. For total all-grade and grade 3&amp;4 trAEs, anti PD-L1 demonstrated lower AE rates vs. anti PD-1 (65% vs. 69% and 12% vs. 16%, respectively). Results were similar for total all-grade and high-grade imAEs (19% vs. 26% and 4% vs. 7%, respectively). The analysis of all-grade individual trAEs showed that anti PD-L1 exhibited lower AE rates vs. anti PD-1 for rash (8% vs. 10.5%), pruritus (9% vs. 12%), diarrhea (8.5% vs. 11%), colitis (1.0% vs. 1.6%), AST (3.0% vs. 5.5%), ALT (3.5% vs. 5.6%), pneumonitis (3.0% vs. 3.9%), hyperthyroidism (0.8% vs. 4.0%) and hypothyroidism (6.0% vs. 8.0%). For grade 3&amp;4 trAEs, differences between anti PD-L1 and anti PD-1 were: 0.6% vs. 1.3% for diarrhea, 0.7% vs. 1.4% for colitis, and 0.9% vs 1.6% for pneumonitis. All-grade imAEs were less frequent for anti PD-L1 vs. anti PD-1 for: rash (6.5% vs. 10%), colitis (1.0% vs. 2.0%), AST (3.5% vs. 3.9%), ALT (2.9% vs. 4.0%), pneumonitis (2.0% vs. 4.0%), hyperthyroidism (2.5% vs. 4.0%) and hypothyroidism (5.5% vs. 9.0%). Similar results were obtained for grade 3&amp;4 imAEs incidences: rash (0.5% vs. 0.9%), diarrhea (0.5% vs. 1.5%), colitis (0.5% vs. 1.1%) and pneumonitis (0.9% vs. 1.4%). Conclusions: Significant differences in trAEs and imAEs rates were shown for anti PD-L1 vs. anti PD-1 monotherapies. Anti PD-L1 demonstrated more favorable safety profiles for total and individual AE rates. Notably, AE rates for pneumonitis and colitis were twice as high for anti PD-1 vs. anti PD-L1 therapies.

Investigation of the Stages of Damage Accumulation in Polymer Composite Materials

This paper presents the results of the study of strength and fracture processes of FRP samples, obtained by vacuum and vacuum-autoclave molding methods. The experimental studies consisted of a three-point bending test with step loading, accompanied by an acoustic emission method. Based on the acoustic emission data recorded using the acoustic-emission software and hardware complex during the experiments, a method for estimating the accumulated damage using various techniques for analyzing acoustic emission parameters was tested. The results of methods for analyzing the power-law coefficient of accumulation of total AE, b-value and density distribution of amplitudes and median frequencies are considered. An estimate of the power-law coefficient of accumulation of the total AE made it possible to determine the bearing capacity of PCM samples. Using the techniques for analyzing the amplitude distribution of the AE signals and the distribution density of the amplitudes and median frequencies of the AE signals, destructive processes in the volume of samples were described and the stages of their damaging were revealed.

A laboratory study of geomechanical characteristics of black shales after sub-critical/super-critical CO2 + brine saturation

This paper presents an experimental study of the impact of CO2–brine–rock interaction on the mechanical properties of shales. Several black shale samples were soaked in sub-critical/super-critical dissolved brine solutions with different adsorption time. Uniaxial compressive strength (UCS) tests together with the AE and SEM technology are used to test the variations of shale’s mechanical properties, crack propagations and microstructures. According to the experimental results, CO2–brine–rock interaction has a great effect on shale’s strength, Young’s modulus and brittleness index which decrease with increasing saturation time. With a 30 days’ adsorption, the UCS and Young’s modulus show large reductions of 60.56 and 52.68% for sub-critical condition and 70.47 and 62.45% for super-critical condition, respectively. AE analysis presents that the total cumulative AE energy increases dramatically after adsorption. Longer saturation time creates more AE energy. Super-critical condition has a higher effect on shale’s mechanical values and acoustic emission energy than the sub-critical condition. Some new micron scale pores appear on SEM images after saturation. Based on the EDS analysis, CO2–brine–rock interaction also causes the increase of C, Na and Fe contents, and the decrease of O, Si, Al and K contents, which prove the occurrence of the dissolution and precipitation.

Impacts of Cyclic Loading and Unloading Rates on Acoustic Emission Evolution and Felicity Effect of Instable Rock Mass

Uniaxial cyclic loading‐unloading compression experiments with schemes of six loading rates and six unloading rates were carried out on the combined testing platform. Impact of loading and unloading rates on rock AE characteristics was revealed. Results show that increasing loading and unloading rates resulted in decreasing total AE rings in the entire rock deformation and failure process. Increasing loading rate decreased the AE rings at loading stages, and increasing unloading rate decreased the AE rings at unloading stages in the same cycle. Total AE counts had a negative linear relationship to the loading and unloading rates. The loading stage was the active period of the AE phenomena, and impacts of the loading rate on the AE characteristics were more apparent. Especially when the loading rate was greater than 2.0 kN/s, brittle failure of rock specimens became noticeable. After the cyclic load reached the uniaxial compressive strength of 1/3∼1/2 times, the rock Felicity effect became more obvious. With the increase of the loading rate, the Felicity ratio decreased in the elastic stage and increased a little in the plastic stage, whereas with the increase of the unloading rate, the Felicity ratio decreased gradually in the elastic stage and remained almost the same in the plastic stage.

Refractive indices of minerals and synthetic compounds

This is a comprehensive compilation of refractive indices of 1933 minerals and 1019 synthetic compounds including exact chemical compositions and references taken from 30 compilations and many mineral and synthetic oxide descriptions. It represents a subset of about 4000 entries used by Shannon and Fischer (2016) to determine the polarizabilities of 270 cations and anions after removing 425 minerals and compounds containing the lone-pair ions (Tl + , Sn 2+ , Pb 2+ , As 3+ , Sb 3+ , Bi 3+ , S 4+ , Se 4+ , Te 4+ , Cl 5+ , Br 5+ , I 5+ ) and uranyl ions, U 6+ . The table lists the empirical composition of the mineral or synthetic compound, the ideal composition of the mineral, the mineral name or synthetic compound, the Dana classes and subclasses extended to include beryllates, aluminates, gallates, germanates, niobates, tantalates, molybdates, tungstates, etc., descriptive notes, e.g., structure polytypes and other information that helps define a particular mineral sample, and the locality of a mineral when known. Finally, we list n x , n y , n z , n Dobs > (all determined at 589.3 nm), n Dcalc >, deviation of observed and calculated mean refractive indices, molar volume V m , corresponding to the volume of one formula unit, anion molar volume V an , calculated from V m divided by the number of anions (O 2− , F − , Cl − , OH − ) and H 2 O in the formula unit, the total polarizability AE >, and finally the reference to the refractive indices for all 2946 entries. The total polarizability of a mineral, AE >, is a useful property that reflects its composition, crystal structure, and chemistry and was calculated using the Anderson-Eggleton relationship α AE = ( n D 2 - 1 ) V m 4 π + ( 4 π 3 - c ) ( n D 2 - 1 ) where c = 2.26 is the electron overlap factor. The empirical polarizabilities and therefore, the combination of refractive indices, compositions, and molar volumes of the minerals and synthetic oxides in the table were verified by a comparison of observed and calculated total polarizabilities, AE > derived from individual polarizabilities of cations and anions. The deviation between observed and calculated refractive indices is

The Analysis for Crystallization of Sn-Pb Alloys Using Acoustic Emission Testing about Wind Turbine Root Materials

Regular researches of system Sn-Pb alloys with use AE are carried out in various crystallization conditions. In the given researches the technique has been used, which allow to divide the signals radiated with plastic deformation and crack's formation and development from each process. In the metals and alloys majority radiation of AE signals begins in the middle of crystallization's area and comes to an end at the moment of the crystallization termination However in a number of materials AE signals have been registered below an excess point on a cooling curve in a firm condition. Essential influence of small impurity on AE feature and is revealed at crystallization AE character with crystallization of pure metals is defined by a kind of a crystal lattice. Linear dependence total AE from cooling rate is established Influence of superfluous and low residual pressure on AE character established with crystallization.

Comment on Tadrous et al.: Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis

Dear Editor, The study by Tadrous et al. [1] identified zoledronic acid as the bisphosphonate with the “highest probability gastrointestinal (GI) adverse events (91 %) and nausea (70 %).” Many clinicians will have been surprised at this finding. First, in contrast to the established mechanisms of upper GI AE following oral preparation of bisphosphonates, there are no known mechanisms explaining GI AEs including nausea when bisphosphonates are administered in IV regimens. Of course, an acute face reaction is not uncommon after zoledronic acid infusion, especially after the first administration and more rarely after the next infusion and this could be accompanied in some cases by stomach upset and nausea. This could have been explored, had the authors included the acute face reaction in their analysis. Second, the frequency of events reported in Table 2 does not seem internally coherent. For alendronate, 54 % reportedly experienced esophageal AEs and 29 % nausea, yet there was no discontinuation of alendronate due to GI adverse events and the total probability of any GI events was stated as 1 %. For zoledronic acid, the authors state that there was no reporting of specific outcomes such as upper GI events or esophageal events, yet cite a probability of any GI event of more than 90 % with discontinuation in 14 %. At any rate, we are left with the impression that the included studies had extreme heterogeneity in their reporting of adverse events and that this may have led to a biased estimate favouring older studies. As a test of this, the authors could have compared the total AE event rate between the placebo groups in the trials. An unforeseen consequence of the conclusions of the study could be a shift away from zoledronic acid, which is now available as a cheaper generic preparation in many countries, to denosumab which remains on patent. Pending a more transparent and robust analysis, we are not persuaded that GI adverse events are more likely with zoledronic acid than with oral bisphosphonates. In reference to adherence, it is surprising the way the authors interpreted their findings when they concluded that annual administration of zoledronic acid may not improve adherence.

Fish oil administration in older adults: is there potential for adverse events? A systematic review of the literature

BackgroundOmega-3 (n-3) fatty acid supplementation is becoming increasingly popular. However given its antithrombotic properties the potential for severe adverse events (SAE) such as bleeding has safety implications, particularly in an older adult population. A systematic review of randomized control trials (RCT) was conducted to explore the potential for SAE and non-severe adverse events (non-SAE) associated with n-3 supplementation in older adults.MethodsA comprehensive search strategy using Medline and a variety of other electronic sources was conducted. Studies investigating the oral administration of n-3 fish oil containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or both against a placebo were sourced. The primary outcome of interest included reported SAE associated with n-3 supplementation. Chi-square analyses were conducted on the pooled aggregate of AEs.ResultsOf the 398 citations initially retrieved, a total of 10 studies involving 994 older adults aged ≥60 years were included in the review. Daily fish oil doses ranged from 0.03 g to 1.86 g EPA and/or DHA with study durations ranging from 6 to 52 weeks. No SAE were reported and there were no significant differences in the total AE rate between groups (n-3 intervention group: 53/540; 9.8%; placebo group: 28/454; 6.2%; p = 0.07). Non-SAE relating to gastrointestinal (GI) disturbances were the most commonly reported however there was no significant increase in the proportion of GI disturbances reported in participants randomized to the n-3 intervention (n-3 intervention group: 42/540 (7.8%); placebo group: 24/454 (5.3%); p = 0.18).ConclusionsThe potential for AEs appear mild-moderate at worst and are unlikely to be of clinical significance. The use of n-3 fatty acids and the potential for SAE should however be further researched to investigate whether this evidence is consistent at higher doses and in other populations. These results also highlight that well-documented data outlining the potential for SAE following n-3 supplementation are limited nor adequately reported to draw definitive conclusions concerning the safety associated with n-3 supplementation. A more rigorous and systematic approach for monitoring and recording AE data in clinical settings that involve n-3 supplementation is required.

Correlation of single nucleotide polymorphisms in NER pathway genes with toxicity in advanced non-small cell lung cancer patients treated with chemotherapy.

e18115 Background: New therapeutic approaches are being developed based on the findings that several genetic abnormalities underlying NSCLC could influence chemosensitivity. We assessed whether polymorphisms in genes of NER pathway, such as ERCC5, ERCC6, MMS19L, CCNH, XPC, RRM1, can affect the tolerability of platinum-based chemotherapy in advanced NSCLC pts. Methods: Eligible pts had histological or cytological confirmed stage IV or IIIB (with malignant pleural effusion) chemo-naïve NSCLC, ECOG PS of 0 to 2 and adequate organ function. Pts received vinorelbine 25 mg/m2 or gemcitabine 1000 mg/m2 on day 1 and 8, or docetaxel 75 mg/m2 or taxel 175 mg/m2 on day 1 plus cisplatin 75 mg/m2 or carboplatin AUC=5 on day 1, every 21 days per cycle, for a maximum of six cycles, unless disease progression or unacceptable toxicity occurred. Hematology and biochemistry analyses were repeated every cycle or before chemotherapy for d8 treatment. Toxicity was classified according to CTC AE 3.0. Venous blood was collected and genomic DNA was isolated. Polymorphisms were assessed. SNPs in ERCC6 (A/G 1413, A/G 1213 and A/G 1097), XPC (T/C 500 and A/C 940), ERCC5 (G/C 1104), RRM1 (−37C/A), CCNH (T/C 270) and MMS19L (G811A) were assessed. Results: Totally 388 pts were included prospectively from Oct 2005 to Mar 2009. Median age was 61 years; 68.8% were male, 36.2% were ECOG PS 1, 33.2% had stage IIIB. The median follow-up time was 18 months (range 8–66 months). Hematological toxicity was the most common AE. SNPs of MMS19L and ERCC6 can predict the AE of chemotherapy in NSCLC,leucopenia (P=0.020), jaundice (P=0.039) by MMS19L. In terms of grade 3-4 AE, SNPs of MMS19L and RRM1 -37C/A have much more predictive effect. SNPs of MMS19L were good at total AE (P=0.042), thrombopenia (P=0.035), SNPs of RRM1 -37C/A were for vomiting (P=0.046) and jaundice (P=0.014). Conclusions: Polymorphisms in ERCC6, MMS19L, RRM1, can predict the tolerability of platinum-based chemotherapy in advanced NSCLC patients. Polymorphisms in other genes of NER pathway, such as ERCC5, CCNH, XPC, have no predictive effect.