Search results for: normal operators

Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Valentina A. Mikhailova, Serguei V. Feskov, Anatoly I. Ivanov

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In the last decade the nonequilibrium charge transfer have attracted considerable interest from the scientific community. Examples of such processes are the charge recombination in excited donor-acceptor complexes and the intramolecular electron transfer from the second excited electronic state. In these reactions the charge transfer proceeds predominantly in the nonequilibrium mode. In the excited donor-acceptor complexes the nuclear nonequilibrium is created by the pump pulse. The intramolecular electron transfer from the second excited electronic state is an example where the nuclear nonequilibrium is created by the forward electron transfer. The kinetics of these nonequilibrium reactions demonstrate a number of peculiar properties. Most important from them are: (i) the absence of the Marcus normal region in the free energy gap law for the charge recombination in excited donor-acceptor complexes, (ii) extremely low quantum yield of thermalized charge separated state in the ultrafast charge transfer from the second excited state, (iii) the nonexponential charge recombination dynamics in excited donor-acceptor complexes, (iv) the dependence of the charge transfer rate constant on the excitation pulse frequency. This report shows that most of these kinetic features can be well reproduced in the framework of stochastic point-transition multichannel model. The model involves an explicit description of the nonequilibrium excited state formation by the pump pulse and accounts for the reorganization of intramolecular high-frequency vibrational modes, for their relaxation as well as for the solvent relaxation. The model is able to quantitatively reproduce complex nonequilibrium charge transfer kinetics observed in modern experiments. The interpretation of the nonequilibrium effects from a unified point of view in the terms of the multichannel point transition stochastic model allows to see similarities and differences of electron transfer mechanism in various molecular donor-acceptor systems and formulates general regularities inherent in these phenomena. The nonequilibrium effects in photoinduced ultrafast charge transfer which have been studied for the last 10 years are analyzed. The methods of suppression of the ultrafast charge recombination, similarities and dissimilarities of electron transfer mechanism in different molecular donor-acceptor systems are discussed. The extremely low quantum yield of the thermalized charge separated state observed in the ultrafast charge transfer from the second excited state in the complex consisting of 1,2,4-trimethoxybenzene and tetracyanoethylene in acetonitrile solution directly demonstrates that its effectiveness can be close to unity. This experimental finding supports the idea that the nonequilibrium charge recombination in the excited donor-acceptor complexes can be also very effective so that the part of thermalized complexes is negligible. It is discussed the regularities inherent to the equilibrium and nonequilibrium reactions. Their fundamental differences are analyzed. Namely the opposite dependencies of the charge transfer rates on the dynamical properties of the solvent. The increase of the solvent viscosity results in decreasing the thermal rate and vice versa increasing the nonequilibrium rate. The dependencies of the rates on the solvent reorganization energy and the free energy gap also can considerably differ. This work was supported by the Russian Science Foundation (Grant No. 16-13-10122).

Keywords: Charge recombination, higher excited states, free energy gap law, nonequilibrium

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Authors: Ching-Yu Liao, Ju-Joan Wong

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Recent years have shown a trend of younger stroke patients and an increase in ischemic strokes with the rise in stroke incidence. This has led to a growing demand for telemedicine, particularly during the COVID-19 pandemic, which has made the need for telemedicine even more urgent. This shift in healthcare is also closely related to advancements in Internet of Things (IoT) technology. Stroke-induced hemiparesis is a significant issue for patients. The medical community believes that if intervention occurs within three to six months of stroke onset, 80% of the residual effects can be restored to normal, a period known as the stroke golden period. During this time, patients undergo treatment and rehabilitation, and neural plasticity is at its best. Lower limb rehabilitation for stroke generally includes exercises such as support standing and walking posture, typically involving the healthy limb to guide the affected limb to achieve rehabilitation goals. Existing gait training aids in hospitals usually involve balance gait, sitting posture training, and precise muscle control, effectively addressing issues of poor gait, insufficient muscle activity, and inability to train independently during recovery. However, home training aids, such as braced and wheeled devices, often rely on the healthy limb to pull the affected limb, leading to lower usage of the affected limb, worsening circular walking, and compensatory movement issues. IoT technology connects devices via the internet to record, receive data, provide feedback, and adjust equipment for intelligent effects. Therefore, this study aims to explore how IoT can be integrated into existing gait training aids to monitor and sensor home rehabilitation movements, improve gait training compensatory issues through real-time feedback, and enable healthcare professionals to quickly understand patient conditions and enhance medical communication. To understand the needs of hemiparetic patients, a review of relevant literature from the past decade will be conducted. From the perspective of user experience, participant observation will be used to explore the use of home training aids by stroke patients and therapists, and interviews with physical therapists will be conducted to obtain professional opinions and practical experiences. Design specifications for home training aids for hemiparetic patients will be summarized. Applying IoT technology to lower limb training aids for stroke hemiparesis can help promote walking function recovery in hemiparetic patients, reduce muscle atrophy, and allow healthcare professionals to immediately grasp patient conditions and adjust gait training plans based on collected and analyzed information. Exploring these potential development directions provides a valuable reference for the further application of IoT technology in the field of medical rehabilitation.

Keywords: stroke, hemiplegia, rehabilitation, gait training, internet of things technology

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Authors: Heba M. Saad Eldien, Ola Abdel-Tawab Hussein, Ahmed Yassein Nassar

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Background: Indomethacin is a non-steroidal anti inflammatory drug. Indomethacin induces an injury to gastrointestinal mucosa in experimental animals and humans and their use is associated with a significant risk of hemorrhage, erosions and perforation of both gastric and intestinal ulcers. The anti-inflammatory action of copper complexes is an important activity of their anti-ulcer effect achieved by their intermediary role as a transport form of copper that allow activation of the several copper-dependent enzymes. Therefore, several copper complexes were synthesized and investigated as promising alternative anti-ulcer therapy. Aim of the work: The purpose of this study was to evaluate a copper chelating complex consisting of egg albumin and copper as one of the copper peptides that can be used as anti-inflammatory agent and effective in ameliorates the hazards of the indomethacin on the histological structure of the fundus of the stomach that could be added to raise the efficacy of the currently used simple and cheap gastric anti-inflammatory drug mucogel. Material &methods: This study was carried out on 40 adult male albino rats,divided equally into 4 groups;Group I(control group) received distilled water,Group II(indomethacin treated group) received (25 mg/kg body weight, oral intubation) once, Group III (mucogel treated group)2 mL/rat once daily, oral incubation, Group IV(copper complex group) 1 mL /rat of 30 gm of copper albumin complex was mixed uniformly with mucogel to 100 mL. Treatment has been started six hour after Induction of Ulcers and continued till the 3rd day. The animals sacrificed and was processed for light, transmission electron microscopy(TEM) and immunostaining for inducible nitric oxide synthase(iNOS). Results: Fundic mucosa of group II, showed exfoliation of epithelial cells lining the gland, discontinuity of surface epithelial cells (ulcer formation), vacuolation and detachment of cells, eosinophilic infiltration and congestion of blood vessels in the lamina propria and submucosa. There was thickening and disarrangement of mucosa, weak positive reaction for PAS and marked increase in the collagen fibers lamina propria and the submucosa of the fundus. TEM revealed degeneration of cheif and parietal cells.Marked increase positive reactive of iNOS in all cells of the fundic gland. Group III showed reconstruction of gastric gland with cystic dilatation and vacuolation, moderate decrease of collagen fibers, reduced the intensity of iNOS while in Group IV healthy mucosa with normal surface lining epithelium and fundic glands, strong positive reaction for PAS, marked decrease of collagen fibers and positive reaction for iNOS. TEM revealed regeneration of cheif and parietal cells. Conclusion: Co treatment of copper-albumin complex seems to be useful for gastric ulcer treatment and ameliorates most of hazards of indomethacin.

Keywords: copper complex, gastric ulcer, indomethacin, rat

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Authors: Feyi Olorunshola

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Over the last few years, the senior travel market has been noted for its potential in the wider tourism industry. The tourism sector includes the hotel and hospitality, travel, transportation, and several other subdivisions to make it economically viable. In particular, the hotel attracts a substantial part of the expenditure in tourism activities as when people plan to travel, suitable accommodation for relaxation, dining, entertainment and so on is paramount to their decision-making. The global retail value of the hotel as of 2018 was significant for tourism. But, despite indications of the hotel to the tourism industry at large, very few empirical studies are available to establish how this sector can leverage on the senior demographic to achieve competitive advantage. Predominantly, studies on the mature market have focused on destination tourism, with a limited investigation on the hotel which makes a significant contribution to tourism. Also, several scholarly studies have demonstrated the importance of the senior travel market to the hotel, yet there is very little empirical research in the field which has explored the driving factors that will become the accepted new normal for this niche segment post-pandemic. Giving that the hotel already operates in a highly saturated business environment, and on top of this pre-existing challenge, the ongoing global health outbreak has further put the sector in a vulnerable position. Therefore, the hotel especially the full-service luxury category must evolve rapidly for it to survive in the current business environment. The hotel can no longer rely on corporate travelers to generate higher revenue since the unprecedented wake of the pandemic in 2020 many organizations have invented a different approach of conducting their businesses online, therefore, the hotel needs to anticipate a significant drop in business travellers. However, the rooms and the rest of the facilities must be occupied to keep their business operating. The way forward for the hotel lies in the leisure sector, but the question now is to focus on the potential demographics of travelers, in this case, the seniors who have been repeatedly recognized as the lucrative market because of increase discretionary income, availability of time and the global population trends. To achieve the study objectives, a mixed-method approach will be utilized drawing on both qualitative (netnography) and quantitative (survey) methods, cognitive and decision-making theories (means-end chain) and competitive theories to identify the salient drivers explaining senior hotel choice and its influence on their decision-making. The target population are repeated seniors’ age 65 years and over who are UK resident, and from the top tourist market to the UK (USA, Germany, and France). Structural equation modelling will be employed to analyze the datasets. The theoretical implication is the development of new concepts using a robust research design, and as well as advancing existing framework to hotel study. Practically, it will provide the hotel management with the latest information to design a competitive marketing strategy and activities to target the mature market post-pandemic and over a long period.

Keywords: competitive advantage, covid-19, full-service hotel, five-star, luxury hotels

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Authors: Rupali Bhatia, Deepthi Nair, Geetika Khanna, Seema Singhal

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Introduction: Genital tract tuberculosis is a chronic disease (caused by reactivation of organisms from systemic distribution of Mycobacterium tuberculosis) that often presents with low grade symptoms and non-specific complaints. Patients with genital tuberculosis are usually young women seeking workup and treatment for infertility. Infertility is the commonest presentation due to involvement of the fallopian tubes, endometrium and ovarian damage with poor ovarian volume and reserve. The diagnosis of genital tuberculosis is difficult because of the fact that it is a silent invader of genital tract. Since tissue cannot be obtained from fallopian tubes, the diagnosis is made by isolation of bacilli from endometrial tissue obtained by endometrial biopsy curettage and/or aspiration. Problems are associated with sampling technique as well as diagnostic modality due to lack of adequate sample volumes and the segregation of the sample for various diagnostic tests resulting in non-uniform distribution of microorganisms. Moreover, lack of an efficient sampling technique universally applicable for all specific diagnostic tests contributes to the diagnostic challenges. Endometrial sampling plays a key role in accurate diagnosis of female genital tuberculosis. It may be done by 2 methods viz. endometrial curettage and endometrial aspiration. Both endometrial curettage and aspirate have their own limitations as curettage picks up strip of the endometrium from one of the walls of the uterine cavity including tubal osteal areas whereas aspirate obtains total tissue with exfoliated cells present in the secretory fluid of the endometrial cavity. Further, sparse and uneven distribution of the bacilli remains a major factor contributing to the limitations of the techniques. The sample that is obtained by either technique is subjected to histopathological examination, AFB staining, culture and PCR. Aim: Comparison of the sampling techniques viz. endometrial biopsy curettage and endometrial aspiration using different laboratory methods of histopathology, cytology, microbiology and molecular biology. Method: In a hospital based observational study, 75 Indian females suspected of genital tuberculosis were selected on the basis of inclusion criteria. The women underwent endometrial tissue sampling using Novaks biopsy curette and Karmans cannula. One part of the specimen obtained was sent in formalin solution for histopathological testing and another part was sent in normal saline for acid fast bacilli smear, culture and polymerase chain reaction. The results so obtained were correlated using coefficient of correlation and chi square test. Result: Concordance of results showed moderate agreement between both the sampling techniques. Among HPE, AFB and PCR, maximum sensitivity was observed for PCR, though the specificity was not as high as other techniques. Conclusion: Statistically no significant difference was observed between the results obtained by the two sampling techniques. Therefore, one may use either EA or EB to obtain endometrial samples and avoid multiple sampling as both the techniques are equally efficient in diagnosing genital tuberculosis by HPE, AFB, culture or PCR.

Keywords: acid fast bacilli (AFB), histopatholgy examination (HPE), polymerase chain reaction (PCR), endometrial biopsy curettage

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Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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Authors: Nicholas Mavrogiannis, Francesca Crivellari, Zachary Gagnon

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Development of low-cost, rapid, sensitive and portable biosensing systems are important for the detection and prevention of disease in developing countries, biowarfare/antiterrorism applications, environmental monitoring, point-of-care diagnostic testing and for basic biological research. Currently, the most established commercially available and widespread assays for portable point of care detection and disease testing are paper-based dipstick and lateral flow test strips. These paper-based devices are often small, cheap and simple to operate. The last three decades in particular have seen an emergence in these assays in diagnostic settings for detection of pregnancy, HIV/AIDS, blood glucose, Influenza, urinary protein, cardiovascular disease, respiratory infections and blood chemistries. Such assays are widely available largely because they are inexpensive, lightweight, and portable, are simple to operate, and a few platforms are capable of multiplexed detection for a small number of sample targets. However, there is a critical need for sensitive, quantitative and multiplexed detection capabilities for point-of-care diagnostics and for the detection and prevention of disease in the developing world that cannot be satisfied by current state-of-the-art paper-based assays. For example, applications including the detection of cardiac and cancer biomarkers and biothreat applications require sensitive multiplexed detection of analytes in the nM and pM range, and cannot currently be satisfied with current inexpensive portable platforms due to their lack of sensitivity, quantitative capabilities and often unreliable performance. In this talk, inexpensive label-free biomolecular detection at liquid interfaces using a newly discovered electrokinetic phenomenon known as fluidic dielectrophoresis (fDEP) is demonstrated. The electrokinetic approach involves exploiting the electrical mismatches between two aqueous liquid streams forced to flow side-by-side in a microfluidic T-channel. In this system, one fluid stream is engineered to have a higher conductivity relative to its neighbor which has a higher permittivity. When a “low” frequency (< 1 MHz) alternating current (AC) electrical field is applied normal to this fluidic electrical interface the fluid stream with high conductivity displaces into the low conductive stream. Conversely, when a “high” frequency (20MHz) AC electric field is applied, the high permittivity stream deflects across the microfluidic channel. There is, however, a critical frequency sensitive to the electrical differences between each fluid phase – the fDEP crossover frequency – between these two events where no fluid deflection is observed, and the interface remains fixed when exposed to an external field. To perform biomolecular detection, two streams flow side-by-side in a microfluidic T-channel: one fluid stream with an analyte of choice and an adjacent stream with a specific receptor to the chosen target. The two fluid streams merge and the fDEP crossover frequency is measured at different axial positions down the resulting liquid

Keywords: biodetection, fluidic dielectrophoresis, interfacial polarization, liquid interface

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Authors: Waqas Ahmed Khan, Faheem Khokhaar

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Air pollution is one of the main perpetrators of climate change. GHGs cause melting of glaciers and cause change in temperature and heavy rain fall many gasses like Formaldehyde is not direct precursor that damage ozone like CO2 or Methane but Formaldehyde (HCHO) form glyoxal (CHOCHO) that has effect on ozone. Countries around the globe have unique air quality monitoring protocols to describe local air pollution. Formaldehyde is a colorless, flammable, strong-smelling chemical that is used in building materials and to produce many household products and medical preservatives. Formaldehyde also occurs naturally in the environment. It is produced in small amounts by most living organisms as part of normal metabolic processes. Pakistan lacks the monitoring facilities on larger scale to measure the atmospheric gasses on regular bases. Formaldehyde is formed from Glyoxal and effect mountain biodiversity and livelihood. So its monitoring is necessary in order to maintain and preserve biodiversity. Objective: Present study is aimed to measure atmospheric HCHO vertical column densities (VCDs) obtained from ground-base and compute HCHO data in Punjab and elevated areas (Rawalpindi & Islamabad) by satellite observation during the time period of 2014-2015. Methodology: In order to explore the spatial distributing of H2CO, various fields campaigns including international scientist by using car Max-Doas. Major focus was on the cities along national highways and industrial region of Punjab Pakistan. Level 2 data product of satellite instruments OMI retrieved by differential optical absorption spectroscopy (DOAS) technique are used. Spatio-temporal distribution of HCHO column densities over main cities and region of Pakistan has been discussed. Results: Results show the High HCHO column densities exceeding permissible limit over the main cities of Pakistan particularly the areas with rapid urbanization and enhanced economic growth. The VCDs value over elevated areas of Pakistan like Islamabad, Rawalpindi is around 1.0×1016 to 34.01×1016 Molecules’/cm2. While Punjab has values revolving around the figure 34.01×1016. Similarly areas with major industrial activity showed high amount of HCHO concentrations. Tropospheric glyoxal VCDs were found to be 4.75 × 1015 molecules/cm2. Conclusion: Results shows that monitoring site surrounded by Margalla hills (Islamabad) have higher concentrations of Formaldehyde. Wind data shows that industrial areas and areas having high economic growth have high values as they provide pathways for transmission of HCHO. Results obtained from this study would help EPA, WHO and air protection departments in order to monitor air quality and further preservation and restoration of mountain biodiversity.

Keywords: air quality, formaldehyde, Max-Doas, vertical column densities (VCDs), satellite instrument, climate change

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Authors: I. M. L. Nadeesha Jayaweera, Adao Alex Trindade

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In choosing a candidate model in likelihood-based modeling via an information criterion, the practitioner is often faced with the difficult task of deciding just how far up the ranked list to look. Motivated by this pragmatic necessity, we construct an uncertainty band for a generalized (model selection) information criterion (GIC), defined as a criterion for which the limit in probability is identical to that of the normalized log-likelihood. This includes common special cases such as AIC & BIC. The method starts from the asymptotic normality of the GIC for the joint distribution of the candidate models in an independent and identically distributed (IID) data framework and proceeds by deriving the (asymptotically) exact distribution of the minimum. The calculation of an upper quantile for its distribution then involves the computation of multivariate Gaussian integrals, which is amenable to efficient implementation via the R package "mvtnorm". The performance of the methodology is tested on simulated data by checking the coverage probability of nominal upper quantiles and compared to the bootstrap. Both methods give coverages close to nominal for large samples, but the bootstrap is two orders of magnitude slower. The methodology is subsequently extended to two other commonly used model structures: regression and time series. In the regression case, we derive the corresponding asymptotically exact distribution of the minimum GIC invoking Lindeberg-Feller type conditions for triangular arrays and are thus able to similarly calculate upper quantiles for its distribution via multivariate Gaussian integration. The bootstrap once again provides a default competing procedure, and we find that similar comparison performance metrics hold as for the IID case. The time series case is complicated by far more intricate asymptotic regime for the joint distribution of the model GIC statistics. Under a Gaussian likelihood, the default in most packages, one needs to derive the limiting distribution of a normalized quadratic form for a realization from a stationary series. Under conditions on the process satisfied by ARMA models, a multivariate normal limit is once again achieved. The bootstrap can, however, be employed for its computation, whence we are once again in the multivariate Gaussian integration paradigm for upper quantile evaluation. Comparisons of this bootstrap-aided semi-exact method with the full-blown bootstrap once again reveal a similar performance but faster computation speeds. One of the most difficult problems in contemporary statistical methodological research is to be able to account for the extra variability introduced by model selection uncertainty, the so-called post-model selection inference (PMSI). We explore ways in which the GIC uncertainty band can be inverted to make inferences on the parameters. This is being attempted in the IID case by pivoting the CDF of the asymptotically exact distribution of the minimum GIC. For inference one parameter at a time and a small number of candidate models, this works well, whence the attained PMSI confidence intervals are wider than the MLE-based Wald, as expected.

Keywords: model selection inference, generalized information criteria, post model selection, Asymptotic Theory

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Authors: Giorgi Chichinadze, David Shengelia, Tamara Tsutsunava, Nikoloz Maisuradze, Giorgi Beridze

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The Jalovchat gabbro intrusive is exposed on the northern and southern slopes of Main Range zone of the Greater Caucasus, on an area about 25km2. It is intruded in Precambrian crystalline schists and amphibolites intensively metamorphose them along the contact zone. The intrusive is represented by hornblende-bearing gabbro, gabbro-norites and norites including thin vein bodies of gabbro-pegmatites, anorthosites and micro-gabbros. Especially should be noted the veins of gabbro-pegmatites with the gigantic (up to 0.5m) hornblende crystals. From this point of view, the Jalovchat gabbroid intrusive is particularly interesting and by its unusual composition has no analog in the Caucasus overall. The comprehensive petrologic and geochemical study of the intrusive was carried out by the authors. The results of investigations are following. Amphiboles correspond to magnesiohastingsite and magnesiohornblende. In hastingsite and hornblende as a result of isovalent isomorphism of Fe2+ by Mg, content of the latter has been increased. By AMF and Na20+K diagrams the intrusive rocks correspond to tholeiitic basalts or to basalts close to it by composition. According to ACM-AMF double diagram the samples distributed in the fields of MORB and alkali cumulates. In TiO2/FeO+Fe2O3, Zr/Y-Zr and Ti-Cr/Ni diagrams and Ti-Cr-Y triangular diagram samples are arranged in the fields of island-arc and mid-oceanic basalts or along the trends reflecting mid-oceanic ridges or island arcs. K2O/TiO2 diagram shows that these rocks belong to normal and enriched MORB type. According to Th/Nb/Y ratio, the Jalovchat intrusive composition corresponds to depleted mantle, but by Sm/Y-Ce/Sm - to the MORB area. Th/Y and Nb/Y ratios coincide with the MORB composition, Th/Yb-Ta/Yb and La/Nb-Ti ratios correspond to N MORB, and Rb/Y and N/Y - to the lower crust formations. Exceptional are Ce/Pb-Ce and Nb/Th-Nb diagrams, showing the area of primitive mantle. Spidergrams are characterized by almost horizontal trend, weakly expressed Eu minimums and by a slight depletion of light REE. Similar are characteristic of typical tholeiit basalts. In comparison to MORB spidergrams, they are characterized by depletion of light REE. Their correlation to the spidergrams of Jalovchat intrusive proves that they are more depleted. The above cited points to the gradual depletion of mantle with the light REE in geological time. The RE and REE diagrams reveal unexpected regularity. In particular, petro-geochemical characteristics of Jalovchat gabbroid intrusive predominantly correspond to MORB, that usually is an anomalous phenomenon, since in ‘ophiolitic’ section magmatic formations represented mainly by gigantic prismatic hornblende-bearing gabbro and gabbro-pegmatite are not indicated. On the basis of petro-mineralogical and petro-geochemical data analysis, the authors consider that the Jalovchat intrusive belongs to the subduction geodynamic type. In the depleted mantle rich in water the MORB rock system has subducted, where the favorable conditions for crystallization of hornblende and especially for its gigantic crystals occurred. It is considered that the Jalovchat intrusive was formed in deep horizons of the Earth’s crust as a result of crystallization of water-bearing Bajocian basalt magma.

Keywords: The Greater Caucasus, gabbro-pegmatite, hornblende-bearing gabbro, petrogenesis

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Authors: Ayesha Mushtaq

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Asthma is a pulmonary disease in which blockade of the airway takes place due to inflammation as a response to certain allergens. Breathing troubles, cough, and dyspnea are one of the few symptoms. Several studies have indicated a significant effect on asthma due to changes in dietary routines. Certain food items, such as oily foods and other materials, are known to cause an increase in the symptoms of asthma. Low dietary intake of fruits and vegetables may be important in relation to asthma prevalence. The objective of this study is to assess and compare the nutritional status of asthmatic and non-asthmatic patients. The significance of this study lies in the factor that it will help nutritionists to arrange a feasible dietary routine for asthmatic patients. This research was conducted at the Pulmonology Department of the Pakistan Institute of Medical Science Islamabad. About thirty hundred thirty-four million people are affected by asthma worldwide. Pakistan is on the verge of being an uplifted urban population and asthma cases are increasingly high these days. Several studies suggest an increase in the Asthmatic patient population due to improper diet. Other studies conducted at different institutions have conducted research on similar topics. These studies have suggested that there is a substantial alteration in the nutritional status of asthmatic and non-Asthmatic patients. This is a cross-sectional study aimed at assessing the nutritious standing of Asthmatic and non-asthmatic patients. This research took place at the Pakistan Institute of Medical Sciences (PIMS), Islamabad, Pakistan. The research included asthmatic and non-asthmatic patients coming to the pulmonology department clinic at the Pakistan Institute of Medical Sciences (PIMS). These patients were aged between 20-60 years. A questionnaire was developed for these patients to estimate their dietary plans in these patients. The methodology included four sections. The first section was the Socio-Demographic profile, which included age, gender, monthly income and occupation. The next section was anthropometric measurements which included the weight, height and body mass index (BMI) of the individual. The next section, section three, was about the biochemical attributes, such as for biochemical profiling, pulmonary function testing (PFT) was performed. In the next section, Dietary habits, which were assessed by using a food frequency questionnaire (FFQ) through food habits and consumption pattern, was assessed. The next section life style data, in which the person's level of physical activity, sleep and smoking habits were assessed. The next section was statistical analysis. All the data obtained from the study were statistically analyzed and assessed. Most of the asthma Patients were females, with weight more than normal or even obese. Body Mass Index (BMI) was higher in asthma Patients than those in non-Asthmatic ones. When the nutritional Values were assessed, we came to know that these patients were low on certain nutrients and their diet included more junk and oily food than healthy vegetables and fruits. Beverages intake was also included in the same assessment. It is evident from this study that nutritional status has a contributory effect on asthma. So, patients on the verge of developing asthma or those who have developed asthma should focus on their diet, maintain good eating habits and take healthy diets, including fruits and vegetables rather than oily foods. Proper sleep may also contribute to the control of asthma.

Keywords: NUTRI, BMI, asthma, food

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Authors: V. Giacometti, R. Mirabelli, V. Patera, D. Pinci, A. Sarti, A. Sciubba, G. Traini, M. Marafini

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The particle therapy (PT) is a very modern technique of non invasive radiotherapy mainly devoted to the treatment of tumours untreatable with surgery or conventional radiotherapy, because localised closely to organ at risk (OaR). Nowadays, PT is available in about 55 centres in the word and only the 20\% of them are able to treat with carbon ion beam. However, the efficiency of the ion-beam treatments is so impressive that many new centres are in construction. The interest in this powerful technology lies to the main characteristic of PT: the high irradiation precision and conformity of the dose released to the tumour with the simultaneous preservation of the adjacent healthy tissue. However, the beam interactions with the patient produce a large component of secondary particles whose additional dose has to be taken into account during the definition of the treatment planning. Despite, the largest fraction of the dose is released to the tumour volume, a non-negligible amount is deposed in other body regions, mainly due to the scattering and nuclear interactions of the neutrons within the patient body. One of the main concerns in PT treatments is the possible occurrence of secondary malignant neoplasm (SMN). While SMNs can be developed up to decades after the treatments, their incidence impacts directly life quality of the cancer survivors, in particular in pediatric patients. Dedicated Treatment Planning Systems (TPS) are used to predict the normal tissue toxicity including the risk of late complications induced by the additional dose released by secondary neutrons. However, no precise measurement of secondary neutrons flux is available, as well as their energy and angular distributions: an accurate characterization is needed in order to improve TPS and reduce safety margins. The project MONDO (MOnitor for Neutron Dose in hadrOntherapy) is devoted to the construction of a secondary neutron tracker tailored to the characterization of that secondary neutron component. The detector, based on the tracking of the recoil protons produced in double-elastic scattering interactions, is a matrix of thin scintillating fibres, arranged in layer x-y oriented. The final size of the object is 10 x 10 x 20 cm3 (squared 250µm scint. fibres, double cladding). The readout of the fibres is carried out with a dedicated SPAD Array Sensor (SBAM) realised in CMOS technology by FBK (Fondazione Bruno Kessler). The detector is under development as well as the SBAM sensor and it is expected to be fully constructed for the end of the year. MONDO will make data tacking campaigns at the TIFPA Proton Therapy Center of Trento, at the CNAO (Pavia) and at HIT (Heidelberg) with carbon ion in order to characterize the neutron component and predict the additional dose delivered on the patients with much more precision and to drastically reduce the actual safety margins. Preliminary measurements with charged particles beams and MonteCarlo FLUKA simulation will be presented.

Keywords: secondary neutrons, particle therapy, tracking detector, elastic scattering

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Authors: Brenda Ravenscroft, Ulemu Luhanga, Bev King

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A comprehensive evaluation of online learning needs to include a blend of educational design, technology use, and online instructional practices that integrate technology appropriately for developing and delivering quality online courses. Research shows that classroom-based evaluation tools do not adequately capture the dynamic relationships between content, pedagogy, and technology in online courses. Furthermore, studies suggest that using classroom evaluations for online courses yields lower than normal scores for instructors, and may affect faculty negatively in terms of administrative decisions. In 2014, the Faculty of Arts and Science at Queen’s University responded to this evidence by seeking an alternative to the university-mandated evaluation tool, which is designed for classroom learning. The Faculty is deeply engaged in e-learning, offering large variety of online courses and programs in the sciences, social sciences, humanities and arts. This paper describes the process by which a new student survey instrument for online courses was developed and piloted, the methods used to analyze the data, and the ways in which the instrument was subsequently adapted based on the results. It concludes with a critical reflection on the challenges of evaluating e-learning. The Student Evaluation of Online Teaching Effectiveness (SEOTE), developed by Arthur W. Bangert in 2004 to assess constructivist-compatible online teaching practices, provided the starting point. Modifications were made in order to allow the instrument to serve the two functions required by the university: student survey results provide the instructor with feedback to enhance their teaching, and also provide the institution with evidence of teaching quality in personnel processes. Changes were therefore made to the SEOTE to distinguish more clearly between evaluation of the instructor’s teaching and evaluation of the course design, since, in the online environment, the instructor is not necessarily the course designer. After the first pilot phase, involving 35 courses, the results were analyzed using Stobart's validity framework as a guide. This process included statistical analyses of the data to test for reliability and validity, student and instructor focus groups to ascertain the tool’s usefulness in terms of the feedback it provided, and an assessment of the utility of the results by the Faculty’s e-learning unit responsible for supporting online course design. A set of recommendations led to further modifications to the survey instrument prior to a second pilot phase involving 19 courses. Following the second pilot, statistical analyses were repeated, and more focus groups were used, this time involving deans and other decision makers to determine the usefulness of the survey results in personnel processes. As a result of this inclusive process and robust analysis, the modified SEOTE instrument is currently being considered for adoption as the standard evaluation tool for all online courses at the university. Audience members at this presentation will be stimulated to consider factors that differentiate effective evaluation of online courses from classroom-based teaching. They will gain insight into strategies for introducing a new evaluation tool in a unionized institutional environment, and methodologies for evaluating the tool itself.

Keywords: evaluation, online courses, student survey, teaching effectiveness

Procedia PDF Downloads 266

Authors: Serena Salvi

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Ageistic stereotypes and practices have become a normal and therefore pervasive phenomenon in various aspects of everyday life. Over the past years, renewed awareness towards self-directed age stereotyping in older adults has given rise to a line of research focused on the potential role of attitudes towards ageing on seniors’ health and functioning. This set of studies has showed how a negative internalisation of ageistic stereotypes would discourage older adults in seeking medical advice, in addition to be associated to negative subjective health evaluation. An important dimension of mental health that is often affected in older adults is represented by sleep quality. Self-reported sleep quality among older adults has shown to be often unreliable when compared to their objective sleep measures. Investigations focused on self-reported sleep quality among older adults have suggested how this portion of the population would tend to accept disrupted sleep if believed to be up to standard for their age. On the other hand, unrealistic expectations, and dysfunctional beliefs towards sleep in ageing, might prompt older adults to report sleep disruption even in the absence of objective disrupted sleep. Objective of this study is to examine an association between personal attitudes towards ageing in adults aged 60+ and dysfunctional sleep related cognition. More in detail, this study aims to investigate a potential association between personal attitudes towards ageing, sleep locus of control and dysfunctional beliefs towards sleep among this portion of the population. Data in this study were statistically analysed in SPSS software. Participants were recruited through the online participants recruitment system Prolific. Inclusion of attention check questions throughout the questionnaire and consistency of responses were looked at. Prior to the commencement of this study, Ethical Approval was granted (ref. 39396). Descriptive statistics were used to determine the frequency, mean, and SDs of the variables. Pearson coefficient was used for interval variables, independent T-test for comparing means between two independent groups, analysis of variance (ANOVA) test for comparing the means in several independent groups, and hierarchical linear regression models for predicting criterion variables based on predictor variables. In this study self-perceptions of ageing were assessed using APQ-B’s subscales, while dysfunctional sleep related cognition was operationalised using the SLOC and the DBAS16 scales. Of the final subscales taken in consideration in the brief version of the APQ questionnaire, Emotional Representations (ER), Control Positive (PC) and Control and Consequences Negative (NC) have shown to be of particularly relevance for the remits of this study. Regression analysis show how an increase in the APQ-B subscale Emotional Representations (ER) predicts an increase in dysfunctional beliefs and attitudes towards sleep in this sample, after controlling for subjective sleep quality, level of depression and chronological age. A second regression analysis showed that APQ-B subscales Control Positive (PC) and Control and Consequences Negative (NC) were significant predictors in the change of variance of SLOC, after controlling for subjective sleep quality, level of depression and dysfunctional beliefs about sleep.

Keywords: sleep-related cognition, perceptions of aging, older adults, sleep quality

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Authors: Golson Mohamed, Yasmine Gamasy, Khaled EL-Khatib, Anas Al-Natour, Shady Fadel, Haytham Rashwan, Haytham Badawy, Nadia Farghaly

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Introduction: Wilm's tumor is the most common malignant renal tumor in children. Much progress has been made in the management of patients with this malignancy over the last 3 decades. Today treatments are based on several trials and studies conducted by the International Society of Pediatric Oncology (SIOP) in Europe and National Wilm's Tumor Study Group (NWTS) in the USA. It is necessary for us to understand why do we follow either of the protocols, NWTS which follows the upfront surgery principle or the SIOP which follows the upfront chemotherapy principle in all stages of the disease. Objective: The aim of is to assess outcome in patients treated with preoperative chemotherapy and patients treated with upfront surgery to compare their effect on overall survival. Study design: to decide which protocol to follow, study was carried out on records for patients aged 1 day to 18 years old suffering from Wilm's tumor who were admitted to Alexandria University Hospital, pediatric oncology, pediatric urology and pediatric surgery departments, with a retrospective survey records from 2010 to 2015, Design and editing of the transfer sheet with a (PRISMA flow study) Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data were fed to the computer and analyzed using IBM SPSS software package version 20.0. (11) Qualitative data were described using number and percent. Quantitative data were described using Range (minimum and maximum), mean, standard deviation and median. Comparison between different groups regarding categorical variables was tested using Chi-square test. When more than 20% of the cells have expected count less than 5, correction for chi-square was conducted using Fisher’s Exact test or Monte Carlo correction. The distributions of quantitative variables were tested for normality using Kolmogorov-Smirnov test, Shapiro-Wilk test, and D'Agstino test, if it reveals normal data distribution, parametric tests were applied. If the data were abnormally distributed, non-parametric tests were used. For normally distributed data, a comparison between two independent populations was done using independent t-test. For abnormally distributed data, comparison between two independent populations was done using Mann-Whitney test. Significance of the obtained results was judged at the 5% level. Results: A significantly statistical difference was observed for survival between the two studied groups favoring the upfront chemotherapy(86.4%)as compared to the upfront surgery group (59.3%) where P=0.009. As regard complication, 20 cases (74.1%) out of 27 were complicated in the group of patients treated with upfront surgery. Meanwhile, 30 cases (68.2%) out of 44 had complications in patients treated with upfront chemotherapy. Also, the incidence of intraoperative complication (rupture) was less in upfront chemotherapy group as compared to upfront surgery group. Conclusion: Upfront chemotherapy has superiority over upfront surgery.As the patient who started with upfront chemotherapy shown, higher survival rate, less percent in complication, less percent needed for radiotherapy, and less rate in recurrence.

Keywords: Wilm's tumor, renal tumor, chemotherapy, surgery

Procedia PDF Downloads 317

Authors: Aditya Sharma

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Profits earned from relative strength strategy of zero-cost portfolio i.e. taking long position in winner stocks and short position in loser stocks from recent past are termed as momentum profits. In recent times, there has been lot of controversy and concern about sources of momentum profits, since the existence of these profits acts as an evidence of earning non-normal returns from publicly available information directly contradicting Efficient Market Hypothesis. Literature review reveals conflicting theories and differing evidences on sources of momentum profits. This paper aims at re-examining the sources of momentum profits in Indian capital markets. The study focuses on assessing the effect of fundamental as well as behavioral sources in order to understand the role of investor behavior in stock returns and suggest (if any) improvements to existing behavioral asset pricing models. This Paper adopts calendar time methodology to calculate momentum profits for 6 different strategies with and without skipping a month between ranking and holding period. For each J/K strategy, under this methodology, at the beginning of each month t stocks are ranked on past j month’s average returns and sorted in descending order. Stocks in upper decile are termed winners and bottom decile as losers. After ranking long and short positions are taken in winner and loser stocks respectively and both portfolios are held for next k months, in such manner that at any given point of time we have K overlapping long and short portfolios each, ranked from t-1 month to t-K month. At the end of period, returns of both long and short portfolios are calculated by taking equally weighted average across all months. Long minus short returns (LMS) are momentum profits for each strategy. Post testing for momentum profits, to study the role market risk plays in momentum profits, CAPM and Fama French three factor model adjusted LMS returns are calculated. In the final phase of studying sources, decomposing methodology has been used for breaking up the profits into unconditional means, serial correlations, and cross-serial correlations. This methodology is unbiased, can be used with the decile-based methodology and helps to test the effect of behavioral and fundamental sources altogether. From all the analysis, it was found that momentum profits do exist in Indian capital markets with market risk playing little role in defining them. Also, it was observed that though momentum profits have multiple sources (risk, serial correlations, and cross-serial correlations), cross-serial correlations plays a major role in defining these profits. The study revealed that momentum profits do have multiple sources however, cross-serial correlations i.e. the effect of returns of other stocks play a major role. This means that in addition to studying the investors` reactions to the information of the same firm it is also important to study how they react to the information of other firms. The analysis confirms that investor behavior does play an important role in stock returns and incorporating both the aspects of investors’ reactions in behavioral asset pricing models help make then better.

Keywords: investor behavior, momentum effect, sources of momentum, stock returns

Procedia PDF Downloads 304

Authors: Iliana Georganta, Clare Deehan, Marysia Thomson, Miriam McDonald, Kerrie McNulty, Anna Strachan, Elizabeth Anderson, Alyaa Mostafa

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Context: A meta-analysis of randomized controlled trials (RCTs) comparing hysterectomy versus endometrial ablation and resection in the management of heavy menstrual bleeding. Objective: To evaluate the clinical efficacy, satisfaction rates and adverse events of hysterectomy compared to more minimally invasive techniques in the treatment of HMB. Evidence Acquisition: A literature search was performed for all RCTs and quasi-RCTs comparing hysterectomy with either endometrial ablation endometrial resection of both. The search had no language restrictions and was last updated in June 2020 using MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials, PubMed, Google Scholar, PsycINFO, Clinicaltrials.gov and Clinical trials. EU. In addition, a manual search of the abstract databases of the European Haemophilia Conference on women's health was performed and further studies were identified from references of acquired papers. The primary outcomes were patient-reported and objective reduction in heavy menstrual bleeding up to 2 years and after 2 years. Secondary outcomes included satisfaction rates, pain, adverse events short and long term, quality of life and sexual function, further surgery, duration of surgery and hospital stay and time to return to work and normal activities. Data were analysed using RevMan software. Evidence synthesis: 12 studies and a total of 2028 women were included (hysterectomy: n = 977 women vs endometrial ablation or resection: n = 1051 women). Hysterectomy was compared with endometrial ablation only in five studies (Lin, Dickersin, Sesti, Jain, Cooper) and endometrial resection only in five studies (Gannon, Schulpher, O’Connor, Crosignani, Zupi) and a mixture of the Ablation and Resection in two studies (Elmantwe, Pinion). Of the 1² studies, 10 reported women’s perception of bleeding symptoms as improved. Meta-analysis showed that women in the hysterectomy group were more likely to show improvement in bleeding symptoms when compared with endometrial ablation or resection up to 2-year follow-up (RR 0.75, 95% CI 0.71 to 0.79, I² = 95%). Objective outcomes of improvement in bleeding also favored hysterectomy. Patient satisfaction was higher after hysterectomy within the 2 years follow-up (RR: 0.90, 95%CI: 0.86 to 0.94, I²:58%), however, there was no significant difference between the two groups at more than 2 years follow up. Sepsis (RR: 0.03, 95% CI 0.002 to 0.56; 1 study), wound infection (RR: 0.05, 95% CI: 0.01 to 0.28, I²: 0%, 3 studies) and Urinary tract infection (UTI) (RR: 0.20, 95% CI: 0.10 to 0.42, I²: 0%, 4 studies) all favoured hysteroscopic techniques. Fluid overload (RR: 7.80, 95% CI: 2.16 to 28.16, I² :0%, 4 studies) and perforation (RR: 5.42, 95% CI: 1.25 to 23.45, I²: 0%, 4 studies) however favoured hysterectomy in the short term. Conclusions: This meta-analysis has demonstrated that endometrial ablation and endometrial resection are both viable options when compared with hysterectomy for the treatment of heavy menstrual bleeding. Hysteroscopic procedures had better outcomes in the short term with fewer adverse events including wound infection, UTI and sepsis. The hysterectomy performed better when measuring more long-term impacts such as recurrence of symptoms, overall satisfaction at two years and the need for further treatment or surgery.

Keywords: menorrhagia, hysterectomy, ablation, resection

Procedia PDF Downloads 155

Authors: Prajakta Patil, Yash Huzurbazar, Abhijeet Shinde

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Aim: To develop a treatment protocol for the management of tinnitus through multi-modality brain stimulation. Methodology: Present study included 33 adults with unilateral (31 subjects) and bilateral (2 subjects) chronic tinnitus with and/or without hearing loss independent of their etiology. The Treatment protocol included 5 consecutive sessions with follow-up of 6 months. Each session was divided into 3 parts: • Pre-treatment: a) Informed consent b) Pitch and loudness matching. • Treatment: Bimanual paper pen task with tinnitus masking for 30 minutes. • Post-treatment: a) Pitch and loudness matching b) Directive counseling and obtaining feedback. Paper-pen task is to be performed bimanually that included carrying out two different writing activities in different context. The level of difficulty of the activities was increased in successive sessions. Narrowband noise of a frequency same as that of tinnitus was presented at 10 dBSL of tinnitus for 30 minutes simultaneously in the ear with tinnitus. Result: The perception of tinnitus was no longer present in 4 subjects while in remaining subjects it reduced to an intensity that its perception no longer troubled them without causing residual facilitation. In all subjects, the intensity of tinnitus decreased by an extent of 45 dB at an average. However, in few subjects, the intensity of tinnitus also decreased by more than 45 dB. The approach resulted in statistically significant reductions in Tinnitus Functional Index and Tinnitus Handicap Inventory scores. The results correlate with pre and post treatment score of Tinnitus Handicap Inventory that dropped from 90% to 0%. Discussion: Brain mapping(qEEG) Studies report that there is multiple parallel overlapping of neural subnetworks in the non-auditory areas of the brain which exhibits abnormal, constant and spontaneous neural activity involved in the perception of tinnitus with each subnetwork and area reflecting a specific aspect of tinnitus percept. The paper pen task and directive counseling are designed and delivered respectively in a way that is assumed to induce normal, rhythmically constant and premeditated neural activity and mask the abnormal, constant and spontaneous neural activity in the above-mentioned subnetworks and the specific non-auditory area. Counseling was focused on breaking the vicious cycle causing and maintaining the presence of tinnitus. Diverting auditory attention alone is insufficient to reduce the perception of tinnitus. Conscious awareness of tinnitus can be suppressed when individuals engage in cognitively demanding tasks of non-auditory nature as the paper pen task used in the present study. To carry out this task selective, divided, sustained, simultaneous and split attention act cumulatively. Bimanual paper pen task represents a top-down activity which underlies brain’s ability to selectively attend to the bimanual written activity as a relevant stimulus and to ignore tinnitus that is the irrelevant stimuli in the present study. Conclusion: The study suggests that this novel treatment approach is cost effective, time saving and efficient to vanish the tinnitus or to reduce the intensity of tinnitus to a negligible level and thereby eliminating the negative reactions towards tinnitus.

Keywords: multi-modality brain stimulation, neural subnetworks, non-auditory areas, paper-pen task, top-down activity

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Authors: Saqib Aziz, Brad Alexander, Christoph Gengnagel, Stefan Weinzierl

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This paper explores a generative design, simulation, and optimization workflow for the integration of acoustical diffuser and/or absorber geometry with embedded coupled Helmholtz-resonators for full-scale 3D printed building components. Large-scale additive manufacturing in conjunction with algorithmic CAD design tools enables a vast amount of control when creating geometry. This is advantageous regarding the increasing demands of comfort standards for indoor spaces and the use of more resourceful and sustainable construction methods and materials. The presented methodology highlights these new technological advancements and offers a multimodal and integrative design solution with the potential for an immediate application in the AEC-Industry. In principle, the methodology can be applied to a wide range of structural elements that can be manufactured by additive manufacturing processes. The current paper focuses on a case study of an application for a biaxial load-bearing beam grillage made of reinforced concrete, which allows for a variety of applications through the combination of additive prefabricated semi-finished parts and in-situ concrete supplementation. The semi-prefabricated parts or formwork bodies form the basic framework of the supporting structure and at the same time have acoustic absorption and diffusion properties that are precisely acoustically programmed for the space underneath the structure. To this end, a hybrid validation strategy is being explored using a digital and cross-platform simulation environment, verified with physical prototyping. The iterative workflow starts with the generation of a parametric design model for the acoustical geometry using the algorithmic visual scripting editor Grasshopper3D inside the building information modeling (BIM) software Revit. Various geometric attributes (i.e., bottleneck and cavity dimensions) of the resonator are parameterized and fed to a numerical optimization algorithm which can modify the geometry with the goal of increasing absorption at resonance and increasing the bandwidth of the effective absorption range. Using Rhino.Inside and LiveLink for Revit, the generative model was imported directly into the Multiphysics simulation environment COMSOL. The geometry was further modified and prepared for simulation in a semi-automated process. The incident and scattered pressure fields were simulated from which the surface normal absorption coefficients were calculated. This reciprocal process was repeated to further optimize the geometric parameters. Subsequently the numerical models were compared to a set of 3D concrete printed physical twin models, which were tested in a .25 m x .25 m impedance tube. The empirical results served to improve the starting parameter settings of the initial numerical model. The geometry resulting from the numerical optimization was finally returned to grasshopper for further implementation in an interdisciplinary study.

Keywords: acoustical design, additive manufacturing, computational design, multimodal optimization

Procedia PDF Downloads 157

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Tsirekidze M., Aprasidze T.

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Introduction: The problem of dissocial behavior is at the heart of the social sciences and psychiatry; however, it should be noted that its psychiatric aspect is little studied, and some issues of the problem are still controversial. This is complicated by the diversity of terminological concepts in defining “dissocial behavior”, “behavioral disorder”, “abnormal behavior”, “deviant behavior”, “delinquent behavior”, etc. In literature, there is no comprehensive definition of the essence of dissociative behavior. Numerous attempts to systematize dissociative disorders should also be considered unsatisfactory, which is primarily related to the lack of solid criteria for defining this group of disorders. According to the clinical classification, dissocial behavior is divided into psychotic and non-psychotic forms. Such differentiation is conditional in nature since it is not always possible to draw precise, clear distinctions between these forms, and in addition, there is a transition of a behavior disorder or so-called intermediate forms. One group of authors distinguishes two main forms of deviant behavior in terms of both theoretical and practical significance - non-pathological and pathological. In recent years, especially, the non-pathological form of behavior disorder has become topical. It refers to a large group of forms of deviant behavior, the emergence of which is associated with psychologically full-fledged reactions of children and adolescents to stressful situations and extreme conditions. According to the authors, its concept is understandable-it is difficult to draw a line between psychologically understandable reactions and psychogenically induced reactive states. In addition, the concept of "normal" child and adolescent is, to some extent, a vague concept, as in medicine, any definition of the norm. From a practical (more precisely, pragmatic) point of view, the term "abnormal behavioral disorder" undoubtedly makes sense, especially for the purpose of forensic psychiatric examination. Non-pathological deviation mainly includes transient situational reactions, microsocial-pedagogical backwardness, and character accentuation.Deviant behavior was predominantly manifested in a non-pathological form, which, in our opinion, is due to the difficult socio-economic situation of the country, moral-ethical deprivation, and expressed frustration. By itself, society is an indicator of deviation. Add to this situation complicated factors such as micro-social-pedagogical leave, unfavorable family environment, and parenting defects. Consideration is also given to the connection of acceptable deviation with the personal structural features of the adolescent. Aim: The topic of our discussion is the dissocial behavior of the non-psychotic register. Methods: We surveyed 120 adolescents with deviant behaviors. 61% of them were diagnosed with various neuropsychiatric disorders. Results: Abnormal forms of deviant behavior were observed in 13%, and non-pathological forms in -69%. A combination of non-pathological and pathological forms was present in 10% of cases. In the case of non-pathological deviation, microsocial-pedagogical acceptance was revealed in 62%, character accentuation in 22%; during the pathological forms, pathological reactions were observed in 21%, and abnormal formation of the person -21%. Conclusion: It should be emphasized that in case of any of the above defects, if the so-called family psychosis, and medical and pedagogical habilitation measures for the adolescent, it is quite possible to prevent the abnormal development of the child's personality, correct his character, regulate behavior and develop positive labor-social relations.

Keywords: dissocial personality, deviant behavior, dissocial, delinquent behavior

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Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

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Authors: Daniel Rowe, Christopher R. Vogel, Richard H. J. Willden

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The University of Oxford’s recirculating water flume is a combined wave and current test tank with a 1 m depth, 1.1 m width, and 10 m long working section, and is capable of flow speeds up to 1 ms−1 . This study documents the hydrodynamic characteristics of the facility in preparation for experimental testing of horizontal axis tidal stream turbine models. The turbine to be tested has a rotor diameter of 0.6 m and is a modified version of one of two model-scale turbines tested in previous experimental campaigns. An Acoustic Doppler Velocimeter (ADV) was used to measure the flow at high temporal resolution at various locations throughout the flume, enabling the spatial uniformity and turbulence flow parameters to be investigated. The mean velocity profiles exhibited high levels of spatial uniformity at the design speed of the flume, 0.6 ms−1 , with variations in the three-dimensional velocity components on the order of ±1% at the 95% confidence level, along with a modest streamwise acceleration through the measurement domain, a target 5 m working section of the flume. A high degree of uniformity was also apparent for the turbulence intensity, with values ranging between 1-2% across the intended swept area of the turbine rotor. The integral scales of turbulence exhibited a far higher degree of variation throughout the water column, particularly in the streamwise and vertical scales. This behaviour is believed to be due to the high signal noise content leading to decorrelation in the sampling records. To achieve more realistic levels of vertical velocity shear in the flume, a simple procedure to practically generate target vertical shear profiles in open-channel flows is described. Here, the authors arranged a series of non-uniformly spaced parallel bars placed across the width of the flume and normal to the onset flow. By adjusting the resistance grading across the height of the working section, the downstream profiles could be modified accordingly, characterised by changes in the velocity profile power law exponent, 1/n. Considering the significant temporal variation in a tidal channel, the choice of the exponent denominator, n = 6 and n = 9, effectively provides an achievable range around the much-cited value of n = 7 observed at many tidal sites. The resulting flow profiles, which we intend to use in future turbine tests, have been characterised in detail. The results indicate non-uniform vertical shear across the survey area and reveal substantial corner flows, arising from the differential shear between the target vertical and cross-stream shear profiles throughout the measurement domain. In vertically sheared flow, the rotor-equivalent turbulence intensity ranges between 3.0-3.8% throughout the measurement domain for both bar arrangements, while the streamwise integral length scale grows from a characteristic dimension on the order of the bar width, similar to the flow downstream of a turbulence-generating grid. The experimental tests are well-defined and repeatable and serve as a reference for other researchers who wish to undertake similar investigations.

Keywords: acoustic doppler Velocimeter, experimental hydrodynamics, open-channel flow, shear profiles, tidal stream turbines

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Authors: Chun-Yu Chen, Kua-Rong Wu, Yu-Cheng Chen, Perng-Jy Tsai

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Cooking fumes are known containing polycyclic aromatic hydrocarbons (PAHs) and aldehydes, and some of them have been proven carcinogenic or possibly carcinogenic to humans. Considering their chronic health effects, long-term exposure data is required for assessing cooking workers’ lifetime health risks. Previous exposure assessment studies, due to both time and cost constraints, mostly were based on the cross-sectional data. Therefore, establishing a long-term exposure data has become an important issue for conducting health risk assessment for cooking workers. An approach was proposed in this study. Here, the generation rates of both PAHs and aldehydes from a cooking process were determined by placing a sampling train exactly under the under the exhaust fan under the both the total enclosure condition and normal operating condition, respectively. Subtracting the concentration collected by the former (representing the total emitted concentration) from that of the latter (representing the hood collected concentration), the fugitive emitted concentration was determined. The above data was further converted to determine the generation rates based on the flow rates specified for the exhaust fan. The determinations of the above generation rates were conducted in a testing chamber with a selected cooking process (deep-frying chicken nuggets under 3 L peanut oil at 200°C). The sampling train installed under the exhaust fan consisted respectively an IOM inhalable sampler with a glass fiber filter for collecting particle-phase PAHs, followed by a XAD-2 tube for gas-phase PAHs. The above was also used to sample aldehydes, however, installed with a filter pre-coated with DNPH, and followed by a 2,4-DNPH-cartridge for collecting particle-phase and gas-phase aldehydes, respectively. PAHs and aldehydes samples were analyzed by GC/MS-MS (Agilent 7890B), and HPLC-UV (HITACHI L-7100), respectively. The obtained generation rates of both PAHs and aldehydes were applied to the near-field/ far-field exposure model to estimate the exposures of cooks (the estimated near-field concentration), and helpers (the estimated far-field concentration). For validating purposes, both PAHs and aldehydes samplings were conducted simultaneously using the same sampling train at both near-field and far-field sites of the testing chamber. The sampling results, together with the use of the mixed-effect model, were used to calibrate the estimated near-field/ far-field exposures. In the present study, the obtained emission rates were further converted to emission factor of both PAHs and aldehydes according to the amount of food oil consumed. Applying the long-term food oil consumption records, the emission rates for both PAHs and aldehydes were determined, and the long-term exposure databanks for cooks (the estimated near-field concentration), and helpers (the estimated far-field concentration) were then determined. Results show that the proposed approach was adequate to determine the generation rates of both PAHs and aldehydes under various fan exhaust flow rate conditions. The estimated near-field/ far-field exposures, though were significantly different from that obtained from the field, can be calibrated using the mixed effect model. Finally, the established long-term data bank could provide a useful basis for conducting long-term exposure assessments for cooking workers exposed to PAHs and aldehydes.

Keywords: aldehydes, cooking oil fumes, long-term exposure assessment, modeling, polycyclic aromatic hydrocarbons (PAHs)

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Authors: Saeid H. Mobini, Monika Lulsdorf, Thomas D. Warkentin

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The length of the breeding cycle from seed to seed is a limiting factor in the development of improved homozygous lines for breeding or recombinant inbred lines (RILs) for genetic analysis. The objective of this research was to accelerate the production of field pea RILs through application of rapid generation technology (RGT). RGT is based on the principle of growing miniature plants in an artificial medium under controlled conditions, and allowing them to produce a few flowers which develop seeds that are harvested prior to normal seed maturity. We aimed to maintain population size and genetic diversity in regeneration cycles. The effects of flurprimidol (a gibberellin synthesis inhibitor), plant density, hydroponic system, scheduled fertilizer applications, artificial light spectrum, photoperiod, and light/dark temperature were evaluated in the development of RILs from a cross between cultivars CDC Dakota and CDC Amarillo. The main goal was to accelerate flowering while reducing maintenance and space costs. In addition, embryo rescue of immature seeds was tested for shortening the seed fill period. Data collected over seven generations included plant height, the percentage of plant survival, flowering rate, seed setting rate, the number of seeds per plant, and time from seed to seed. Applying 0.6 µM flurprimidol reduced the internode length. Plant height was decreased to approximately 32 cm allowing for higher plant density without a delay in flowering and seed setting rate. The three light systems (T5 fluorescent bulbs, LEDs, and High Pressure Sodium +Metal-halide lamp) evaluated did not differ significantly in terms of flowering time in field pea. Collectively, the combination of 0.6 µM flurprimidol, 217 plant. m-2, 20 h photoperiod, 21/16 oC light/dark temperature in a hydroponic system with vermiculite substrate, applying scheduled fertilizer application based on growth stage, and 500 µmole.m-2.s-1 light intensity using T5 bulbs resulted in 100% of plants flowering within 34 ± 3 days and 96.5% of plants completed seed setting in 68.2 ± 3.6 days, i.e., 30-45 days/generation faster than conventional single seed descent (SSD) methods. These regeneration cycles were reproducible consistently. Hence, RGT could double (5.3) generations per year, using 3% occupying space, compared to SSD (2-3 generation/year). Embryo rescue of immature seeds at 7-8 mm stage, using commercial fertilizer solutions (Holland’s Secret™) showed seed setting rate of 95%, while younger embryos had lower germination rate. Mature embryos had a seed setting rate of 96.5% without either hormones or sugar added. So, considering the higher cost of embryo rescue using a procedure which requires skill, additional materials, and expenses, it could be removed from RGT with a further cost saving, and the process could be stopped between generations if required.

Keywords: field pea, flowering, rapid regeneration, recombinant inbred lines, single seed descent

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Authors: Sachin Mulmi Shrestha, Xin Fang, Hui Ye, Lihua Ren, Qinghua Ji, Ruihua Shi

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Background: Esophageal squamous cell carcinoma (ESCC) is a tumor arising from esophageal epithelial cells and is one of the major disease subtype in Asian countries, including China. Esophageal cancer is the 7th highest incidence based on the 2020 data of GLOBOCAN. The pathogenesis of cancer is still not well understood as many molecular and genetic basis of esophageal carcinogenesis has yet to be clearly elucidated. Circular RNAs are RNA molecules that are formed by back-splicing covalently joined 3′- and 5′-endsrather than canonical splicing, and recent data suggest circular RNAs could sponge miRNAs and are enriched with functional miRNA binding sites. Hence, we studied the mechanism of circular RNA, its biological function, and the relationship between microRNA in the carcinogenesis of ESCC. Methods: 4 pairs of normal and esophageal cancer tissues were collected in Zhongda hospital, affiliated to Southeast University, and high-throughput RNA sequencing was done. The result revealed that circ_0032746 was upregulated, and thus we selected circ_0032746 for further study. The backsplice junction of circRNA was validated by sanger sequence, and stability was determined by RNASE R assay. The binding site of circRNA and microRNA was predicted by circinteractome,mirandaand RNAhybrid database. Furthermore, circRNA was silenced by siRNA and then by lentivirus. The regulatory axis of circ0032746/miR4270 was validated by shRNA, mimic, and inhibitor transfection. Then, in vitro experiments were performed to assess the role of circ0032746 on proliferation (CCK-8 assay and colon formation assay), migration and invasion (Transewell assay), and apoptosis of ESCC. Results: The upregulated circ0032746 was validated in 9 pairs of tissues and 5 types of cell lines by qPCR, which showed high expression and was statistically significant (P<0.005) ). Upregulated circ0032746 was silenced by shRNA, which showed significant knockdown in KYSE 30 and TE-1 cell lines expression compared to control. Nuclear and cytoplasmic mRNA fraction experiment displayed the cytoplasmic location of circ0032746. The sponging of miR4270 was validated by co-transfection of sh-circ0032746 and mimic or inhibitor. Transfection with mimic showed the decreased expression of circ_0032746, whereas inhibitor inhibited the result. In vitro experiments showed that silencing of circ_0032746 inhibited the proliferation, migration, and invasion compared to the negative control group. The apoptosis was seen higher in a knockdown group than in the control group. Furthermore, 11 common mircoRNA target mRNAs were predicted by Targetscan, MirTarbase, and miRanda database, which may further play role in the pathogenesis. Conclusion: Our results showed that novel circ_0032746 is upregulated in ESCC and plays role in itsoncogenicity. Silencing of circ_0032746 inhibits the proliferation and migration of ESCC whereas increases the apoptosis of cancer cells. Hence, circ0032746 acts as an oncogene in ESCC by sponging with miR4270 and could be a potential biomarker in the diagnosis of ESCC in the future.

Keywords: circRNA, esophageal squamous cell carcinoma, microRNA, upregulated

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Authors: Rafia S. Al-lamki, Jun Wang, Simon Pacey, Jordan Pober, John R. Bradley

Abstract:

Tumor necrosis factor alpha (TNF), signaling through TNFR2, may act an autocrine growth factor for renal tubular epithelial cells. Clear cell renal carcinomas (ccRCC) contain cancer stem cells (CSCs) that give rise to progeny which form the bulk of the tumor. CSCs are rarely in cell cycle and, as non-proliferating cells, resist most chemotherapeutic agents. Thus, recurrence after chemotherapy may result from the survival of CSCs. Therapeutic targeting of both CSCs and the more differentiated bulk tumor populations may provide a more effective strategy for treatment of RCC. In this study, we hypothesized that TNFR2 signaling will induce CSCs in ccRCC to enter cell cycle so that treatment with ligands that engage TNFR2 will render CSCs susceptible to chemotherapy. To test this hypothesis, we have utilized wild-type TNF (wtTNF) or specific muteins selective for TNFR1 (R1TNF) or TNFR2 (R2TNF) to treat either short-term organ cultures of ccRCC and adjacent normal kidney (NK) tissue or cultures of CD133+ cells isolated from ccRCC and adjacent NK, hereafter referred to as stem cell-like cells (SCLCs). The effect of cyclophosphamide (CP), currently an effective anticancer agent, was tested on CD133+SCLCs from ccRCC and NK before and after R2TNF treatment. Responses to TNF were assessed by flow cytometry (FACS), immunofluorescence, and quantitative real-time PCR, TUNEL, and cell viability assays. Cytotoxic effect of CP was analyzed by Annexin V and propidium iodide staining with FACS. In addition, we assessed the effect of TNF on isolated SCLCs differentiation using a three-dimensional (3D) culture system. Clinical samples of ccRCC contain a greater number SCLCs compared to NK and the number of SCSC increases with higher tumor grade. Isolated SCLCs show expression of stemness markers (oct4, Nanog, Sox2, Lin28) but not differentiation markers (cytokeratin, CD31, CD45, and EpCAM). In ccRCC organ cultures, wtTNF and R2TNF increase CD133 and TNFR2 expression and promote cell cycle entry whereas wtTNF and R1TNF increase TNFR1 expression and promote cell death of SCLCs. Similar findings are observed in SCLCs isolated from NK but the effect was greater in SCLCs isolated from ccRCC. Application of CP distinctly triggered apoptotic and necrotic cell death in SLCSs pre-treatment with R2TNF as compared to CP treatment alone, with SCLCs from ccRCC more sensitive to CP compared to SLCS from NK. Furthermore, TNF promotes differentiation of SCLCs to an epithelial phenotype in 3D cultures, confirmed by cytokeratin expression and loss of stemness markers Nanog and Sox2. The differentiated cells show positive expression of TNF and TNFR2. These findings provide evidence that selective engagement of TNFR2 drive CSCs to cell proliferation/differentiation, and targeting of cycling cells with TNFR2 agonist in combination with anti-cancer agents may be a potential therapy for RCC.

Keywords: cancer stem cells, ccRCC, cell cycle, cell death, TNF, TNFR1, TNFR2, CD133

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Authors: Walter W. Loo

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China declared the “zero discharge rules which leave no toxics into our living environment and deliver blue sky, green land and clean water to many generations to come”. The achievement of ZWD will provide conservation of water, soil and energy and provide drastic increase in Gross Domestic Products (GDP). Our society’s engine needs a major tune up; it is sputtering. ZWD is achieved in world’s space stations – no toxic air emission and the water is totally recycled and solid wastes all come back to earth. This is all done with solar power. These are all achieved under extreme temperature, pressure and zero gravity in space. ZWD can be achieved on earth under much less fluctuations in temperature, pressure and normal gravity environment. ZWD systems are not expensive and will have multiple beneficial returns on investment which are both financially and environmentally acceptable. The paper will include successful case histories since the mid-1970s. ZWD discharge can be applied to the following types of projects: nuclear and coal fire power plants with a closed loop system that will eliminate thermal water discharge; residential communities with wastewater treatment sump and recycle the water use as a secondary water supply; waste water treatment Plants with complete water recycling including water distillation to produce distilled water by very economical 24-hours solar power plant. Landfill remediation is based on neutralization of landfilled gas odor and preventing anaerobic leachate formation. It is an aerobic condition which will render landfill gas emission explosion proof. Desert development is the development of recovering soil moisture from soil and completing a closed loop water cycle by solar energy within and underneath an enclosed greenhouse. Salt-alkali land development can be achieved by solar distillation of salty shallow water into distilled water. The distilled water can be used for soil washing and irrigation and complete a closed loop water cycle with energy and water conservation. Heavy metals remediation can be achieved by precipitation of dissolved toxic metals below the plant or vegetation root zone by solar electricity without pumping and treating. Soil and groundwater remediation - abandoned refineries, chemical and pesticide factories can be remediated by in-situ electrobiochemical and bioventing treatment method without pumping or excavation. Toxic organic chemicals are oxidized into carbon dioxide and heavy metals precipitated below plant and vegetation root zone. New water sources: low temperature distilled water can be recycled for repeated use within a greenhouse environment by solar distillation; nano bubble water can be made from the distilled water with nano bubbles of oxygen, nitrogen and carbon dioxide from air (fertilizer water) and also eliminate the use of pesticides because the nano oxygen will break the insect growth chain in the larvae state. Three dimensional high yield greenhouses can be constructed by complete water recycling using the vadose zone soil as a filter with no farming wastewater discharge.

Keywords: greenhouses, no discharge, remediation of soil and water, wastewater

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Authors: Vinodhini Elangovan, Jen Heng Pek

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Background: An ectopic pregnancy is defined as any pregnancy implanted outside of the endometrial cavity. Cornual pregnancy, a rare variety of ectopic pregnancies, is seen in about 2-4% of ectopic pregnancies. It develops in the interstitial portion of the fallopian tube and invades through the uterine wall. This case describes a third-trimester cornual pregnancy that resulted in a uterine rupture. Case: A 38-year old Chinese lady was brought to the Emergency Department (ED) as a standby case for hypotension. She was 30+6 weeks pregnant (Gravida 3, Parous 1). Her past obstetric history included a live birth delivered via lower segment Caesarean section due to non-reassuring fetal status in 2002 and a miscarriage in 2012. She developed generalized abdominal pain. There was no per vaginal bleeding or leaking liquor. There was also no fever, nausea, vomiting, constipation, diarrhea, or urinary symptoms. On arrival in the ED, she was pale, diaphoretic, and lethargic. She had generalized tenderness with guarding and rebound over her abdomen. Point of care ultrasound was performed and showed a large amount of intra-abdominal free fluid, and the fetal heart rate was 170 beats per minute. The point of care hemoglobin was 7.1 g/dL, and lactate was 6.8 mmol/L. The patient’s blood pressure dropped precipitously to 50/36 mmHg, and her heart rate went up to 141 beats per minute. The clinical impression was profound shock secondary to uterine rupture. Intra-operatively, there was extensive haemoperitoneum, and the fetus was seen in the abdominal cavity. The fetus was delivered immediately and handed to the neonatal team. On exploration of the uterus, the point of rupture was at the left cornual region where the placenta was attached to. Discussion: Cornual pregnancies are difficult to diagnose pre-operatively with low ultrasonographic sensitivity and hence are commonly confused with normal intrauterine pregnancies. They pose a higher risk of rupture and hemorrhage compared to other types of ectopic pregnancies. In very rare circumstances, interstitial pregnancies can result in a viable fetus. Uterine rupture resulting in hemorrhagic shock is a true obstetric emergency that can result in significant morbidity and mortality for the patient and the fetus, and early diagnosis in the emergency department is crucial. The patient in this case presented with known risk factors of multiparity, advanced maternal age, and previous lower segment cesarean section, which increased the suspicion of uterine rupture. Ultrasound assessment may be beneficial to any patient who presents with symptoms and a history of uterine surgery to assess the possibility of uterine dehiscence or rupture. Management of a patient suspected of uterine rupture should be systematic in the emergency department and follow an ABC approach. Conclusion: This case demonstrates the importance for an emergency physician to maintain the suspicion for ectopic pregnancy even at advanced gestational ages. It also highlights how even though all emergency physicians may not be qualified to do a detailed pelvic ultrasound, it is essential for them to be competent with a point of care ultrasound to make a prompt diagnosis of conditions such as uterine rupture.

Keywords: cornual ectopic , ectopic pregnancy, emergency medicine, obstetric emergencies

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