Search results for: slow onset hypoxia

Authors: Vivek Garg, Brajendra S. Sengar, Gaurav Siddharth, Nisheka Anadkat, Amitesh Kumar, Shailendra Kumar, Shaibal Mukherjee

Abstract:

CuInGaSe (CIGSe) is the dominant thin film solar cell technology. The band alignment of Buffer/CIGSe interface is one of the most crucial parameters for solar cell performance. In this article, the valence band offset (VBOff) and conduction band offset (CBOff) values of Cu(In0.70Ga0.30)Se/ 1 at.% Ga: Mg0.25Zn0.75O (GMZO) heterojunction, grown by dual ion beam sputtering system (DIBS), are calculated to understand the carrier transport mechanism at the heterojunction for the realization of all sputtered buffer-less solar cells. To determine the valence band offset (VBOff), ∆E_V at GMZO/CIGSe heterojunction interface, the standard method based on core-level photoemission is utilized. The value of ∆E_V can be evaluated by considering common core-level peaks. In our study, the values of (Valence band onset)VBOn, obtained by linear extrapolation method for GMZO and CIGSe films are calculated to be 2.86 and 0.76 eV. In the UPS spectra peak positions of Se 3d is observed in UPS spectra at 54.82 and 54.7 eV for CIGSe film and GMZO/CIGSe interface respectively, while the peak position of Mg 2p is observed at 50.09 and 50.12 eV for GMZO and GMZO/CIGSe interface respectively. The optical band gap of CIGSe and GMZO are obtained from absorption spectra procured from spectroscopic ellipsometry are 1.26 and 3.84 eV respectively. The calculated average values of ∆E_v and ∆E_C are estimated to be 2.37 and 0.21 eV, respectively, at room temperature. The calculated positive conduction band offset termed as a spike at the absorber junction is the required criterion for the high-efficiency solar cells for the efficient charge extraction from the junction. So we can conclude that the above study confirms GMZO thin films grown by the dual ion beam sputtering system are the suitable candidate for the CIGSe thin films based ultra-thin buffer-less solar cells. We investigated the band-offset properties at the GMZO/CIGSe heterojunction to verify the suitability of the GMZO for the realization of the buffer-less solar cells. The calculated average values of ∆E_V and ∆E_C are estimated to be 2.37 and 0.21 eV, respectively, at room temperature. The calculated positive conduction band offset termed as a spike at the absorber junction is the required criterion for the high-efficiency solar cells for the efficient charge extraction from the junction. So we can conclude that the above study confirms GMZO thin films grown by the dual ion beam sputtering system are the suitable candidate for the CIGSe thin films based ultra-thin buffer-less solar cells. Acknowledgment: We are thankful to DIBS, EDX, and XRD facility equipped at Sophisticated Instrument Centre (SIC) at IIT Indore. The authors B.S.S and A.K acknowledge CSIR and V.G acknowledge UGC, India for their fellowships. B.S.S is thankful to DST and IUSSTF for BASE Internship Award. Prof. Shaibal Mukherjee is thankful to DST and IUSSTF for BASE Fellowship and MEITY YFRF award. This work is partially supported by DAE BRNS, DST CERI, and DST-RFBR Project under India-Russia Programme of Cooperation in Science and Technology. We are thankful to Mukul Gupta for SIMS facility equipped at UGC-DAE Indore.

Keywords: CIGSe, DIBS, GMZO, solar cells, UPS

Procedia PDF Downloads 269

Authors: Marta Malo, Carlota Soto, Carmen García-Rosales, Teresa Hernández

Abstract:

SiC based composites are candidates for possible use as structural and functional materials in the future fusion reactors, the main role is intended for the blanket modules. In the blanket, the neutrons produced in the fusion reaction slow down and their energy is transformed into heat in order to finally generate electrical power. In the blanket design named Dual Coolant Lead Lithium (DCLL), a PbLi alloy for power conversion and tritium breeding circulates inside hollow channels called Flow Channel Inserts (FCIs). These FCI must protect the steel structures against the highly corrosive PbLi liquid and the high temperatures, but also provide electrical insulation in order to minimize magnetohydrodynamic interactions of the flowing liquid metal with the high magnetic field present in a magnetically confined fusion environment. Due to their nominally high temperature and radiation stability as well as corrosion resistance, SiC is the main choice for the flow channel inserts. The significantly lower manufacturing cost presents porous SiC (dense coating is required in order to assure protection against corrosion and as a tritium barrier) as a firm alternative to SiC/SiC composites for this purpose. This application requires the materials to be exposed to high radiation levels and extreme temperatures, conditions for which previous studies have shown noticeable changes in both the microstructure and the electrical properties of different types of silicon carbide. Both initial properties and radiation/temperature induced damage strongly depend on the crystal structure, polytype, impurities/additives that are determined by the fabrication process, so the development of a suitable material requires full control of these variables. For this work, several SiC samples with different percentage of porosity and sintering additives have been manufactured by the so-called sacrificial template method at the Ceit-IK4 Technology Center (San Sebastián, Spain), and characterized at Ciemat (Madrid, Spain). Electrical conductivity was measured as a function of temperature before and after irradiation with 1.8 MeV electrons in the Ciemat HVEC Van de Graaff accelerator up to 140 MGy (~ 2·10 -5 dpa). Radiation-induced conductivity (RIC) was also examined during irradiation at 550 ºC for different dose rates (from 0.5 to 5 kGy/s). Although no significant RIC was found in general for any of the samples, electrical conductivity increase with irradiation dose was observed to occur for some compositions with a linear tendency. However, first results indicate enhanced radiation resistance for coated samples. Preliminary thermogravimetric tests of selected samples, together with posterior XRD analysis allowed interpret radiation-induced modification of the electrical conductivity in terms of changes in the SiC crystalline structure. Further analysis is needed in order to confirm this.

Keywords: DCLL blanket, electrical conductivity, flow channel insert, porous SiC, radiation damage, thermal stability

Procedia PDF Downloads 196

Authors: Ruth Goldschmidt, Vyacheslav Kalchenko, Lilah Agemy, Rachel Elmoalem, Avigdor Scherz

Abstract:

Vascular Targeted Photodynamic therapy (VTP) is a new modality for selective cancer treatment that leads to the complete tumor ablation. A photosensitizer, a bacteriochlorophyll derivative in our case, is first administered to the patient and followed by the illumination of the tumor area, by a near-IR laser for its photoactivation. The photoactivated drug releases reactive oxygen species (ROS) in the circulation, which reacts with blood cells and the endothelium leading to the occlusion of the blood vasculature. If the blood vessels are only partially closed, the tumor may recover, and cancer cells could survive. On the other hand, excessive treatment may lead to toxicity of healthy tissues nearby. Simultaneous VTP monitoring and image processing independent of the photoexcitation laser has not yet been reported, to our knowledge. Here we present a method for blood flow monitoring, using a real-time laser speckle imaging (RTLSI) in the tumor during VTP. We have synthesized over the years a library of bacteriochlorophyll derivatives, among them WST11 and STL-6014. Both are water soluble derivatives that are retained in the blood vasculature through their partial binding to HSA. WST11 has been approved in Mexico for VTP treatment of prostate cancer at a certain drug dose, and time/intensity of illumination. Application to other bacteriochlorophyll derivatives or other cancers may require different treatment parameters (such as light/drug administration). VTP parameters for STL-6014 are still under study. This new derivative mainly differs from WST11 by its lack of the central Palladium, and its conjugation to an Arg-Gly-Asp (RGD) sequence. RGD is a tumor-specific ligand that is used for targeting the necrotic tumor domains through its affinity to αVβ3 integrin receptors. This enables the study of cell-targeted VTP. We developed a special RTLSI module, based on Labview software environment for data processing. The new module enables to acquire raw laser speckle images and calculate the values of the laser temporal statistics of time-integrated speckles in real time, without additional off-line processing. Using RTLSI, we could monitor the tumor’s blood flow following VTP in a CT26 colon carcinoma ear model. VTP with WST11 induced an immediate slow down of the blood flow within the tumor and a complete final flow arrest, after some sporadic reperfusions. If the irradiation continued further, the blood flow stopped also in the blood vessels of the surrounding healthy tissue. This emphasizes the significance of light dose control. Using our RTLSI system, we could prevent any additional healthy tissue damage by controlling the illumination time and restrict blood flow arrest within the tumor only. In addition, we found that VTP with STL-6014 was the most effective when the photoactivation was conducted 4h post-injection, in terms of tumor ablation success in-vivo and blood vessel flow arrest. In conclusion, RTSLI application should allow to optimize VTP efficacy vs. toxicity in both the preclinical and clinical arenas.

Keywords: blood vessel occlusion, cancer treatment, photodynamic therapy, real time imaging

Procedia PDF Downloads 216

Authors: Akeel A. Shah, Tong Zhang

Abstract:

Computational approaches to learning the properties of materials are commonplace, motivated by the need to screen or design materials for a given application, e.g., semiconductors and energy storage. Experimental approaches can be both time consuming and costly. Unfortunately, computational approaches such as ab-initio electronic structure calculations and classical or ab-initio molecular dynamics are themselves can be too slow for the rapid evaluation of materials, often involving thousands to hundreds of thousands of candidates. Machine learning assisted approaches have been developed to overcome the time limitations of purely physics-based approaches. These approaches, on the other hand, require large volumes of data for training (hundreds of thousands on many standard data sets such as QM7b). This means that they are limited by how quickly such a large data set of physics-based simulations can be established. At high fidelity, such as configuration interaction, composite methods such as G4, and coupled cluster theory, gathering such a large data set can become infeasible, which can compromise the accuracy of the predictions - many applications require high accuracy, for example band structures and energy levels in semiconductor materials and the energetics of charge transfer in energy storage materials. In order to circumvent this problem, multi-fidelity approaches can be adopted, for example the Δ-ML method, which learns a high-fidelity output from a low-fidelity result such as Hartree-Fock or density functional theory (DFT). The general strategy is to learn a map between the low and high fidelity outputs, so that the high-fidelity output is obtained a simple sum of the physics-based low-fidelity and correction, Although this requires a low-fidelity calculation, it typically requires far fewer high-fidelity results to learn the correction map, and furthermore, the low-fidelity result, such as Hartree-Fock or semi-empirical ZINDO, is typically quick to obtain, For high-fidelity outputs the result can be an order of magnitude or more in speed up. In this work, a new multi-fidelity approach is developed, based on a graph convolutional network (GCN) combined with semi-supervised learning. The GCN allows for the material or molecule to be represented as a graph, which is known to improve accuracy, for example SchNet and MEGNET. The graph incorporates information regarding the numbers of, types and properties of atoms; the types of bonds; and bond angles. They key to the accuracy in multi-fidelity methods, however, is the incorporation of low-fidelity output to learn the high-fidelity equivalent, in this case by learning their difference. Semi-supervised learning is employed to allow for different numbers of low and high-fidelity training points, by using an additional GCN-based low-fidelity map to predict high fidelity outputs. It is shown on 4 different data sets that a significant (at least one order of magnitude) increase in accuracy is obtained, using one to two orders of magnitude fewer low and high fidelity training points. One of the data sets is developed in this work, pertaining to 1000 simulations of quinone molecules (up to 24 atoms) at 5 different levels of fidelity, furnishing the energy, dipole moment and HOMO/LUMO.

Keywords: .materials screening, computational materials, machine learning, multi-fidelity, graph convolutional network, semi-supervised learning

Procedia PDF Downloads 18

Authors: N. Reza Pour, S. Chuah, T. Vo

Abstract:

Background: Vertebral artery dissection (VAD) is a rare complication of pregnancy. It can occur spontaneously or following a traumatic event. The pathogenesis is unclear. Predisposing factors include chronic hypertension, Marfan’s syndrome, fibromuscular dysplasia, vasculitis and cystic medial necrosis. Physiological changes of pregnancy have also been proposed as potential mechanisms of injury to the vessel wall. The clinical presentation varies and it can present as a headache, neck pain, diplopia, transient ischaemic attack, or an ischemic stroke. Isolated cases of VAD in pregnancy and puerperium have been reported in the literature. One case was found to have posterior circulation stroke as a result of bilateral VAD and labour was induced at 37 weeks gestation for preeclampsia. Another patient at 38 weeks with severe neck pain that persisted after induction for elevated blood pressure and arteriography showed right VAD postpartum. A single case of lethal VAD in pregnancy with subsequent massive subarachnoid haemorrhage has been reported which was confirmed by the autopsy. Case Presentation: We report two cases of vertebral artery dissection in pregnancy. The first patient was a 32-year-old primigravida presented at the 38th week of pregnancy with the onset of early labour and blood pressure (BP) of 130/70 on arrival. After 2 hours, the patient developed a severe headache with blurry vision and BP was 238/120. Despite treatment with an intravenous antihypertensive, she had eclamptic fit. Magnesium solfate was started and Emergency Caesarean Section was performed under the general anaesthesia. On the second day after the operation, she developed left-sided neck pain. Magnetic Resonance Imaging (MRI) angiography confirmed a short segment left vertebral artery dissection at the level of C3. The patient was treated with aspirin and remained stable without any neurological deficit. The second patient was a 33-year-old primigavida who was admitted to the hospital at 36 weeks gestation with BP of 155/105, constant headache and visual disturbances. She was medicated with an oral antihypertensive agent. On day 4, she complained of right-sided neck pain. MRI angiogram revealed a short segment dissection of the right vertebral artery at the C2-3 level. Pregnancy was terminated on the same day with emergency Caesarean Section and anticoagulation was started subsequently. Post-operative recovery was complicated by rectus sheath haematoma requiring evacuation. She was discharged home on Aspirin without any neurological sequelae. Conclusion: Because of collateral circulation, unilateral vertebral artery dissections may go unrecognized and may be more common than suspected. The outcome for most patients is benign, reflecting the adequacy of the collateral circulation in young patients. Spontaneous VAD is usually treated with anticoagulation or antiplatelet therapy for a minimum of 3-6 months to prevent future ischaemic events, allowing the dissection to heal on its own. We had two cases of VAD in the context of hypertensive disorders of pregnancy with an acceptable outcome. A high level of vigilance is required particularly with preeclamptic patients presenting with head/neck pain to allow an early diagnosis. This is as we hypothesize, early and aggressive management of vertebral artery dissection may potentially prevent further complications.

Keywords: eclampsia, preeclampsia, pregnancy, Vertebral Artery Dissection

Procedia PDF Downloads 266

Authors: Nervana Elbakary, Sami Ouanes, Sadaf Riaz, Oraib Abdallah, Islam Mahran, Noriya Al-Khuzaei, Yassin Eltorki

Abstract:

Major Depressive Disorder (MDD) requires therapeutic interventions during the initial month after being diagnosed for better disease outcomes. International guidelines recommend a duration of 4–12 weeks for an initial antidepressant (IAD) trial at an optimized dose to get a response. If depressive symptoms persist after this duration, guidelines recommend switching, augmenting, or combining strategies as the next step. Most patients with MDD in the mental health setting have been labeled incorrectly as treatment-resistant where in fact they have not been subjected to an adequate trial of guideline-recommended therapy. Premature discontinuation of IAD due to ineffectiveness can cause unfavorable consequences. Avoiding irrational practices such as subtherapeutic doses of IAD, premature switching between the ADs, and refraining from unjustified polypharmacy can help the disease to go into a remission phase We aimed to determine the prevalence and the patterns of strategies applied after an IAD was changed because of a suboptimal response as a primary outcome. Secondary outcomes included the median survival time on IAD before any change; and the predictors that were associated with IAD change. This was a retrospective cross- sectional study conducted in Mental Health Services in Qatar. A dataset between January 1, 2018, and December 31, 2019, was extracted from the electronic health records. Inclusion and exclusion criteria were defined and applied. The sample size was calculated to be at least 379 patients. Descriptive statistics were reported as frequencies and percentages, in addition, to mean and standard deviation. The median time of IAD to any change strategy was calculated using survival analysis. Associated predictors were examined using two unadjusted and adjusted cox regression models. A total of 487 patients met the inclusion criteria of the study. The average age for participants was 39.1 ± 12.3 years. Patients with first experience MDD episode 255 (52%) constituted a major part of our sample comparing to the relapse group 206(42%). About 431 (88%) of the patients had an occurrence of IAD change to any strategy before end of the study. Almost half of the sample (212 (49%); 95% CI [44–53%]) had their IAD changed less than or equal to 30 days. Switching was consistently more common than combination or augmentation at any timepoint. The median time to IAD change was 43 days with 95% CI [33.2–52.7]. Five independent variables (age, bothersome side effects, un-optimization of the dose before any change, comorbid anxiety, first onset episode) were significantly associated with the likelihood of IAD change in the unadjusted analysis. The factors statistically associated with higher hazard of IAD change in the adjusted analysis were: younger age, un-optimization of the IAD dose before any change, and comorbid anxiety. Because almost half of the patients in this study changed their IAD as early as within the first month, efforts to avoid treatment failure are needed to ensure patient-treatment targets are met. The findings of this study can have direct clinical guidance for health care professionals since an optimized, evidence-based use of AD medication can improve the clinical outcomes of patients with MDD; and also, to identify high-risk factors that could worsen the survival time on IAD such as young age and comorbid anxiety

Keywords: initial antidepressant, dose optimization, major depressive disorder, comorbid anxiety, combination, augmentation, switching, premature discontinuation

Procedia PDF Downloads 140

Authors: Rajashekar Badam, Vedarajan Raman, Noriyoshi Matsumi

Abstract:

Efficiency of energy converting and storage systems like fuel cells and Li-Air battery principally depended on oxygen reduction reaction (ORR) which occurs at cathode. As the kinetics of the ORR is very slow, it becomes the rate determining step. Exploring carbon substrates for enhancing the dispersion and activity of the metal catalyst and commercially viable simple preparation method is a very crucial area of research in the field of energy materials. Hence, many researchers made large number of carbon-based ORR materials today. But, there are hardly few studies on the effect of interaction between Pt-carbon and carbon-electrolyte on activity. In this work, we have prepared functionalized carbon-based Pt catalyst (Pt-FAB) with enhanced interfacial properties that lead to efficient ORR catalysis. The present work deals with a single-pot method to exfoliate and functionalized acetylene black with enhanced interaction with Pt as well as electrolyte. Acetylene black was functionalized and exfoliated using a facile single pot acid treatment method. The resulted FAB was further decorated with Pt-nano particles (Pt-np). The TEM images of Pt-FAB with uniformly decorated Pt-np of ~3 nm. Further, XPS studies of Pt 4f peak revealed that Pt0 peak was shifted by 0.4 eV in Pt-FAB compared to binding energy of typical Pt⁰ found in Pt/C. The shift can be ascribed to the modulation of electronic state and strong electronic interaction of Pt with carbon. Modulated electronic structure of Pt and strong electronic interaction of Pt with FAB enhances the catalytic activity and durability respectively. To understand the electrode electrolyte interface, electrochemical impedance spectroscopy was carried out. These measurements revealed that the charge transfer resistance of electrode to electrolyte for Pt-FAB is 10 times smaller than that of conventional Pt/C. The interaction with electrolyte helps reduce the interface boundaries, which in turn affects the overall catalytic performance of the electrode. Cyclic voltammetric measurements in 0.1M HClO₄ aq. at a potential scan rate of 50 mVs-1 was employed to evaluate electrochemical surface area (ECSA) of Pt. ECSA of Pt-FAB was found to be as high as 67.2 m²g⁻¹. The three-electrode system showed very high ORR catalytic activity. Mass activity at 0.9 V vs. RHE showed 460 A/g which is much higher than the DOE target values for the year 2020. Further, it showed enhanced performance by showing 723 mW/cm² of highest power density and 1006 mA/cm² of current density at 0.6 V in fuel cell single cell type configuration and 1030 mAhg⁻¹ of rechargeable capacity in Li air battery application. The higher catalytic activity can be ascribed to the improved interaction of FAB with Pt and electrolyte. The aforementioned results evince that Pt-FAB will be a promising cathode material for efficient ORR with significant cyclability for its application in fuel cells and Li-Air batteries. In conclusion, a disordered material was prepared from AB and was systematically characterized. The extremely high ORR activity and ease of preparation make it competent for replacing commercially available ORR materials.

Keywords: functionalized acetylene black, oxygen reduction reaction, fuel cells, Functionalized battery

Procedia PDF Downloads 99

Authors: D. Ficai, A. Ficai, D. Gudovan, I. A. Gudovan, I. Ardelean, R. Trusca, E. Andronescu, V. Mitran, A. Cimpean

Abstract:

In the last years, scientists struggled hardly to mimic bone structures to develop implants and biostructures which present higher biocompatibility and reduced rejection rate. One way to obtain this goal is to use similar materials as that of bone, namely collagen/hydroxyapatite composite materials. However, it is very important to tailor both compositions but also the microstructure of the bone that would ensure both the optimal osteointegartion and the mechanical properties required by the application. In this study, new collagen/hydroxyapatites composite materials doped with Cu, Li, Mn, Zn were successfully prepared. The synthesis method is described below: weight the Ca(OH)₂ mass, i.e., 7,3067g, and ZnCl₂ (0.134g), CuSO₄ (0.159g), LiCO₃ (0.133g), MnCl₂.4H₂O (0.1971g), and suspend in 100ml distilled water under magnetic stirring. The solution thus obtained is added a solution of NaH₂PO₄*H2O (8.247g dissolved in 50ml distilled water) under slow dropping of 1 ml/min followed by adjusting the pH to 9.5 with HCl and finally filter and wash until neutral pH. The as-obtained slurry was dried in the oven at 80°C and then calcined at 600°C in order to ensure a proper purification of the final product of organic phases, also inducing a proper sterilization of the mixture before insertion into the collagen matrix. The collagen/hydroxyapatite composite materials are tailored from morphological point of view to optimize their biocompatibility and bio-integration against mechanical properties whereas the addition of the dopants is aimed to improve the biological activity of the samples. The addition of transitional metals can improve the biocompatibility and especially the osteoblasts adhesion (Mn²⁺) or to induce slightly better osteoblast differentiation of the osteoblast, Zn²⁺ being a cofactor for many enzymes including those responsible for cell differentiation. If the amount is too high, the final material can become toxic and lose all of its biocompatibility. In order to achieve a good biocompatibility and not reach the cytotoxic effect, the amount of transitional metals added has to be maintained at low levels (0.5% molar). The amount of transitional metals entering into the elemental cell of HA will be verified using inductively-coupled plasma mass spectrometric system. This highly sensitive technique is necessary, because, at such low levels of transitional metals, the difference between biocompatible and cytotoxic is a very thin line, thus requiring proper and thorough investigation using a precise technique. In order to determine the structure and morphology of the obtained composite materials, IR spectroscopy, X-Ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-Ray Spectrometry (EDS) were used. Acknowledgment: The present work was possible due to the EU-funding grant POSCCE-A2O2.2.1-2013-1, Project No. 638/12.03.2014, code SMIS-CSNR 48652. The financial contribution received from the national project “Biomimetic porous structures obtained by 3D printing developed for bone tissue engineering (BIOGRAFTPRINT), No. 127PED/2017 is also highly acknowledged.

Keywords: collagen, composite materials, hydroxyapatite, bone tissue engineering

Procedia PDF Downloads 196

Authors: Rachana Tank, Donald. M. Lyall, Kristin Flegal, Joey Ward, Jonathan Cavanagh

Abstract:

Alzheimer’s research UK estimates by 2050, 2 million individuals will be living with Late Onset Alzheimer’s disease (LOAD). However, individuals experience considerable cognitive deficits and brain pathology over decades before reaching clinically diagnosable LOAD and studies have utilised gene candidate studies such as genome wide association studies (GWAS) and polygenic risk (PGR) scores to identify high risk individuals and potential pathways. This investigation aims to determine whether high genetic risk of LOAD is associated with worse brain MRI and cognitive performance in healthy older adults within the UK Biobank cohort. Previous studies investigating associations of PGR for LOAD and measures of MRI or cognitive functioning have focused on specific aspects of hippocampal structure, in relatively small sample sizes and with poor ‘controlling’ for confounders such as smoking. Both the sample size of this study and the discovery GWAS sample are bigger than previous studies to our knowledge. Genetic interaction between loci showing largest effects in GWAS have not been extensively studied and it is known that APOE e4 poses the largest genetic risk of LOAD with potential gene-gene and gene-environment interactions of e4, for this reason we  also analyse genetic interactions of PGR with the APOE e4 genotype. High genetic loading based on a polygenic risk score of 21 SNPs for LOAD is associated with worse brain MRI and cognitive outcomes in healthy individuals within the UK Biobank cohort. Summary statistics from Kunkle et al., GWAS meta-analyses (case: n=30,344, control: n=52,427) will be used to create polygenic risk scores based on 21 SNPs and analyses will be carried out in N=37,000 participants in the UK Biobank. This will be the largest study to date investigating PGR of LOAD in relation to MRI. MRI outcome measures include WM tracts, structural volumes. Cognitive function measures include reaction time, pairs matching, trail making, digit symbol substitution and prospective memory. Interaction of the APOE e4 alleles and PGR will be analysed by including APOE status as an interaction term coded as either 0, 1 or 2 e4 alleles. Models will be adjusted partially for adjusted for age, BMI, sex, genotyping chip, smoking, depression and social deprivation. Preliminary results suggest PGR score for LOAD is associated with decreased hippocampal volumes including hippocampal body (standardised beta = -0.04, P = 0.022) and tail (standardised beta = -0.037, P = 0.030), but not with hippocampal head. There were also associations of genetic risk with decreased cognitive performance including fluid intelligence (standardised beta = -0.08, P<0.01) and reaction time (standardised beta = 2.04, P<0.01). No genetic interactions were found between APOE e4 dose and PGR score for MRI or cognitive measures. The generalisability of these results is limited by selection bias within the UK Biobank as participants are less likely to be obese, smoke, be socioeconomically deprived and have fewer self-reported health conditions when compared to the general population. Lack of a unified approach or standardised method for calculating genetic risk scores may also be a limitation of these analyses. Further discussion and results are pending.

Keywords: Alzheimer's dementia, cognition, polygenic risk, MRI

Procedia PDF Downloads 106

Authors: Igor A. Krichtafovitch

Abstract:

The evolutionary processes are not linear. Long periods of quiet and slow development turn to rather rapid emergences of new species and even phyla. During Cambrian explosion, 22 new phyla were added to the previously existed 3 phyla. Contrary to the common credence the natural selection or a survival of the fittest cannot be accounted for the dominant evolution vector which is steady and accelerated advent of more complex and more intelligent living organisms. Neither Darwinism nor alternative concepts including panspermia and intelligent design propose a satisfactory solution for these phenomena. The proposed hypothesis offers a logical and plausible explanation of the evolutionary processes in general. It is based on two postulates: a) the Biosphere is a single living organism, all parts of which are interconnected, and b) the Biosphere acts as a giant biological supercomputer, storing and processing the information in digital and analog forms. Such supercomputer surpasses all human-made computers by many orders of magnitude. Living organisms are the product of intelligent creative action of the biosphere supercomputer. The biological evolution is driven by growing amount of information stored in the living organisms and increasing complexity of the biosphere as a single organism. Main evolutionary vector is not a survival of the fittest but an accelerated growth of the computational complexity of the living organisms. The following postulates may summarize the proposed hypothesis: biological evolution as a natural life origin and development is a reality. Evolution is a coordinated and controlled process. One of evolution’s main development vectors is a growing computational complexity of the living organisms and the biosphere’s intelligence. The intelligent matter which conducts and controls global evolution is a gigantic bio-computer combining all living organisms on Earth. The information is acting like a software stored in and controlled by the biosphere. Random mutations trigger this software, as is stipulated by Darwinian Evolution Theories, and it is further stimulated by the growing demand for the Biosphere’s global memory storage and computational complexity. Greater memory volume requires a greater number and more intellectually advanced organisms for storing and handling it. More intricate organisms require the greater computational complexity of biosphere in order to keep control over the living world. This is an endless recursive endeavor with accelerated evolutionary dynamic. New species emerge when two conditions are met: a) crucial environmental changes occur and/or global memory storage volume comes to its limit and b) biosphere computational complexity reaches critical mass capable of producing more advanced creatures. The hypothesis presented here is a naturalistic concept of life creation and evolution. The hypothesis logically resolves many puzzling problems with the current state evolution theory such as speciation, as a result of GM purposeful design, evolution development vector, as a need for growing global intelligence, punctuated equilibrium, happening when two above conditions a) and b) are met, the Cambrian explosion, mass extinctions, happening when more intelligent species should replace outdated creatures.

Keywords: supercomputer, biological evolution, Darwinism, speciation

Procedia PDF Downloads 154

Authors: Lakshmi Rao Kandukuri, Mamata Deenadayal, Suma Prasad, Bipin Sethi, Srinadh Buragadda, Lalji Singh

Abstract:

Worldwide; at least 7.6 million children are born annually with severe genetic or congenital malformations and among them 90% of these are born in mid and low-income countries. Precise prevalence data are difficult to collect, especially in developing countries, owing to the great diversity of conditions and also because many cases remain undiagnosed. The genetic and congenital disorder is the second most common cause of infant and childhood mortality and occurs with a prevalence of 25-60 per 1000 births. The higher prevalence of genetic diseases in a particular community may, however, be due to some social or cultural factors. Such factors include the tradition of consanguineous marriage, which results in a higher rate of autosomal recessive conditions including congenital malformations, stillbirths, or mental retardation. Genetic diseases can vary in severity, from being fatal before birth to requiring continuous management; their onset covers all life stages from infancy to old age. Those presenting at birth are particularly burdensome and may cause early death or life-long chronic morbidity. Genetic testing for several genetic diseases identifies changes in chromosomes, genes, or proteins. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person's chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use and more are being developed. Chromosomal abnormalities are the major cause of human suffering, which are implicated in mental retardation, congenital malformations, dysmorphic features, primary and secondary amenorrhea, reproductive wastage, infertility neoplastic diseases. Cytogenetic evaluation of patients is helpful in the counselling and management of affected individuals and families. We present here especially chromosomal abnormalities which form a major part of genetic disease burden in India. Different programmes on chromosome research and human reproductive genetics primarily relate to infertility since this is a major public health problem in our country, affecting 10-15 percent of couples. Prenatal diagnosis of chromosomal abnormalities in high-risk pregnancies helps in detecting chromosomally abnormal foetuses. Such couples are counselled regarding the continuation of pregnancy. In addition to the basic research, the team is providing chromosome diagnostic services that include conventional and advanced techniques for identifying various genetic defects. Other than routine chromosome diagnosis for infertility, also include patients with short stature, hypogonadism, undescended testis, microcephaly, delayed developmental milestones, familial, and isolated mental retardation, and cerebral palsy. Thus, chromosome diagnostics has found its applicability not only in disease prevention and management but also in guiding the clinicians in certain aspects of treatment. It would be appropriate to affirm that chromosomes are the images of life and they unequivocally mirror the states of human health. The importance of genetic counseling is increasing with the advancement in the field of genetics. The genetic counseling can help families to cope with emotional, psychological, and medical consequences of genetic diseases.

Keywords: India, chromosome abnormalities, genetic disorders, cytogenetic study

Procedia PDF Downloads 306

Authors: Maria Ledinskaya

Abstract:

This paper is part case study and part literature review. It seeks to introduce Agile, Lean, and Hybrid project management concepts from business, software development, and manufacturing fields to museum conservation by looking at their practical application on a recent conservation project at the Sainsbury Centre for Visual Arts. The author outlines the advantages of leaner and more agile conservation practices in today’s faster, less certain, and more budget-conscious museum climate where traditional project structures are no longer as relevant or effective. The Morris Collection Conservation Project was carried out in 2019-2021 in Norwich, UK, and concerned the remedial conservation of around 150 Abstract Constructivist artworks bequeathed to the Sainsbury Centre by private collectors Michael and Joyce Morris. It was a medium-sized conservation project of moderate complexity, planned and delivered in an environment with multiple known unknowns – unresearched collection, unknown conditions and materials, unconfirmed budget. The project was later impacted by the COVID-19 pandemic, introducing indeterminate lockdowns, budget cuts, staff changes, and the need to accommodate social distancing and remote communications. The author, then a staff conservator at the Sainsbury Centre who acted as project manager on the Morris Project, presents an incremental, iterative, and value-based approach to managing a conservation project in an uncertain environment. The paper examines the project from the point of view of Traditional, Agile, Lean, and Hybrid project management. The author argues that most academic writing on project management in conservation has focussed on a Traditional plan-driven approach – also known as Waterfall project management – which has significant drawbacks in today’s museum environment due to its over-reliance on prediction-based planning and its low tolerance to change. In the last 20 years, alternative Agile, Lean and Hybrid approaches to project management have been widely adopted in software development, manufacturing, and other industries, although their recognition in the museum sector has been slow. Using examples from the Morris Project, the author introduces key principles and tools of Agile, Lean, and Hybrid project management and presents a series of arguments on the effectiveness of these alternative methodologies in museum conservation, including the ethical and practical challenges to their implementation. These project management approaches are discussed in the context of consequentialist, relativist, and utilitarian developments in contemporary conservation ethics. Although not intentionally planned as such, the Morris Project had a number of Agile and Lean features which were instrumental to its successful delivery. These key features are identified as distributed decision-making, a co-located cross-disciplinary team, servant leadership, focus on value-added work, flexible planning done in shorter sprint cycles, light documentation, and emphasis on reducing procedural, financial, and logistical waste. Overall, the author’s findings point in favour of a hybrid model, which combines traditional and alternative project processes and tools to suit the specific needs of the project.

Keywords: agile project management, conservation, hybrid project management, lean project management, waterfall project management

Procedia PDF Downloads 61

Authors: Elmira Aliyeva, Dadash Huseynov, Robert Hoogendoorn, Salomon Kroonenberg

Abstract:

The Kura River is the major water artery in the Southern Caucasus; it is a third river in the Caspian Sea basin in terms of length and size of the catchment area, the second in terms of the water budget, and the first in the volume of sediment load. Understanding of major controls on the Kura fluvial- deltaic system is valuable for efficient management of the highly populated river basin and coastal zone. We have studied grain size of sediments accumulated in the river channels and delta and dated by 210Pb method, astrophotographs, old topographic and geological maps, and archive data. At present time sediments are supplied by the Kura River to the Caspian Sea through three distributary channels oriented north-east, south-east, and south-west. The river is dominated by the suspended load - mud, silt, very fine sand. Coarse sediments are accumulated in the distributaries, levees, point bar, and delta front. The annual suspended sediment budget in the time period 1934-1952 before construction of the Mingechavir water reservoir in 1953 in the Kura River midstream area was 36 mln.t/yr. From 1953 to 1964, the suspended load has dropped to 12 mln.t/yr. After regulation of the Kura River discharge the volume of suspended load transported via north-eastern channel reduced from 35% of the total sediment amount to 4%, and through the main south-eastern channel increased from 65% to 96% with further fall to 56% due to creation of new south-western channel in 1964. Between 1967-1976 the annual sediment budget of the Kura River reached 22,5 mln. t/yr. From 1977 to 1986, the sediment load carried by the Kura River dropped to 17,6 mln.t/yr. The historical data show that between 1860 and 1907, during relatively stable Caspian Sea level two channels - N and SE, appear to have distributed an equal amount of sediments as seen from the bilateral geometry of the delta. In the time period 1907-1929, two new channels - E and NE, appeared. The growth of three delta lobes - N, NE, and SE, and rapid progradation of the delta has occurred on the background of the Caspian Sea level rise as a result of very high sediment supply. Since 1929 the Caspian Sea level decline was followed by the progradation of the delta occurring along the SE channel. The eastern and northern channels have been silted up. The slow rate of progradation at its initial stage was caused by the artificial reduction in the sediment budget. However, the continuous sea-level fall has brought to this river bed gradient increase, high erosional rate, increase in the sediment supply, and more rapid progradation. During the subsequent sea-level rise after 1977 accompanied by the decrease in the sediment budget, the southern part of the delta has turned into a complex of small, shallow channels oriented to the south. The data demonstrate that behaviour of the Kura fluvial – deltaic system and variations in the sediment budget besides anthropogenic regulation are strongly governed by the Caspian Sea level very rapid changes.

Keywords: anthropogenic control on sediment budget, Caspian sea-level variations, Kura river sediment load, morphology of the Kura river delta, sedimentation in the Kura river delta

Procedia PDF Downloads 148

Authors: Hirseland Andreas, Kerschbaumer Lukas

Abstract:

In the case of Germany, there are about one million long-term unemployed – a figure that did not vary much during the past years. These long-term unemployed did not benefit from the prospering labor market while most short-term unemployed did. Instead, they are continuously dependent on welfare and sometimes precarious short-term employment, experiencing work poverty. Long-term unemployment thus turns into a main obstacle to become employed again, especially if it is accompanied by other impediments such as low-level education (school/vocational), poor health (especially chronical illness), advanced age (older than fifty), immigrant status, motherhood or engagement in care for other relatives. As can be shown by this current research project, in these cases the chance to regain employment decreases to near nil. Almost two-thirds of all welfare recipients have multiple impediments which hinder a successful transition from welfare back to sustainable and sufficient employment. Prospective employers are unlikely to hire long-term unemployed with additional impediments because they evaluate potential employees on their negative signaling (e.g. low-level education) and the implicit assumption of unproductiveness (e.g. poor health, age). Some findings of the panel survey “Labor market and social security” (PASS) carried out by the Institute of Employment Research (the research institute of the German Federal Labor Agency) spread a ray of hope, showing that unlikely does not necessarily mean impossible. The presentation reports on current research on these very scarce “success stories” of unlikely transitions from long-term unemployment to work and how these cases were able to perform this switch against all odds. The study is based on a mixed-method design. Within the panel survey (~15,000 respondents in ~10,000 households), only 66 cases of such unlikely transitions were observed. These cases have been explored by qualitative inquiry – in depth-interviews and qualitative network techniques. There is strong evidence that sustainable transitions are influenced by certain biographical resources like habits of network use, a set of informal skills and particularly a resilient way of dealing with obstacles, combined with contextual factors rather than by job-placement procedures promoted by Job-Centers according to activation rules or by following formal paths of application. On the employer’s side small and medium-sized enterprises are often found to give job opportunities to a wider variety of applicants, often based on a slow but steadily increasing relationship leading to employment. According to these results it is possible to show and discuss some limitations of (German) activation policies targeting the labor market and their impact on welfare dependency and long-term unemployment. Based on these findings, indications for more supportive small-scale measures in the field of labor-market policies are suggested to help long-term unemployed with multiple impediments to overcome their situation (e.g. organizing small-scale-structures and low-threshold services to encounter possible employers on a more informal basis like “meet and greet”).

Keywords: against-all-odds, mixed-methods, Welfare State, long-term unemployment

Procedia PDF Downloads 352

Authors: Jonathan Kissi, Baozhen Dai, Wisdom W. K. Pomegbe, Abdul-Basit Kassim

Abstract:

Protecting patient’s digital information is a growing concern for healthcare institutions as people nowadays perpetually live their lives through telemedicine services. These telemedicine services have been confronted with several determinants that hinder their successful implementations, especially in developing countries. Identifying such determinants that influence the acceptance of telemedicine services is also a problem for healthcare professionals. Despite the tremendous increase in telemedicine services, its adoption, and use has been quite slow in some healthcare settings. Generally, it is accepted in today’s globalizing world that the success of telemedicine services relies on users’ satisfaction. Satisfying health professionals and patients are one of the crucial objectives of telemedicine success. This study seeks to investigate the determinants that influence health professionals’ intention to utilize telemedicine services in clinical activities in a sub-Saharan African country in West Africa (Ghana). A hybridized model comprising of health adoption models, including technology acceptance theory, diffusion of innovation theory, and protection of motivation theory, were used to investigate these quandaries. The study was carried out in four government health institutions that apply and regulate telemedicine services in their clinical activities. A structured questionnaire was developed and used for data collection. Purposive and convenience sampling methods were used in the selection of healthcare professionals from different medical fields for the study. The collected data were analyzed based on structural equation modeling (SEM) approach. All selected constructs showed a significant relationship with health professional’s behavioral intention in the direction expected from prior literature including perceived usefulness, perceived ease of use, management strategies, financial sustainability, communication channels, patients security threat, patients privacy risk, self efficacy, actual service use, user satisfaction, and telemedicine services systems securities threat. Surprisingly, user characteristics and response efficacy of health professionals were not significant in the hybridized model. The findings and insights from this research show that health professionals are pragmatic when making choices for technology applications and also their willingness to use telemedicine services. They are, however, anxious about its threats and coping appraisals. The identified significant constructs in the study may help to increase efficiency, quality of services, quality patient care delivery, and satisfactory user satisfaction among healthcare professionals. The implantation and effective utilization of telemedicine services in the selected hospitals will aid as a strategy to eradicate hardships in healthcare services delivery. The service will help attain universal health access coverage to all populace. This study contributes to empirical knowledge by identifying the vital factors influencing health professionals’ behavioral intentions to adopt telemedicine services. The study will also help stakeholders of healthcare to formulate better policies towards telemedicine service usage.

Keywords: telemedicine service, perceived usefulness, perceived ease of use, management strategies, security threats

Procedia PDF Downloads 131

Authors: Deepak Loura

Abstract:

Production and productivity of several crops in the country continue to be adversely affected by biotic (e.g., Insect-pests and diseases) and abiotic (e.g., water temperature and salinity) stresses. Over-dependence on pesticides and other chemicals is economically non-viable for the resource-poor farmers of our country. Further, pesticides can potentially affect human and environmental safety. While traditional breeding techniques and proper- management strategies continue to play a vital role in crop improvement, we need to judiciously use biotechnology approaches for the development of genetically modified crops addressing critical problems in the improvement of crop plants for sustainable agriculture. Modern biotechnology can help to increase crop production, reduce farming costs, and improve food quality and the safety of the environment. Genetic engineering is a new technology which allows plant breeders to produce plants with new gene combinations by genetic transformation of crop plants for improvement of agronomic traits. Advances in recombinant DNA technology have made it possible to have genes between widely divergent species to develop genetically modified or genetically engineered plants. Plant genetic engineering provides the strength to harness useful genes and alleles from indigenous microorganisms to enrich the gene pool for developing genetically modified (GM) crops that will have inbuilt (inherent) resistance to insect pests, diseases, and abiotic stresses. Plant biotechnology has made significant contributions in the past 20 years in the development of genetically engineered or genetically modified crops with multiple benefits. A variety of traits have been introduced in genetically engineered crops which include (i) herbicide resistance. (ii) pest resistance, (iii) viral resistance, (iv) slow ripening of fruits and vegetables, (v) fungal and bacterial resistance, (vi) abiotic stress tolerance (drought, salinity, temperature, flooding, etc.). (vii) quality improvement (starch, protein, and oil), (viii) value addition (vitamins, micro, and macro elements), (ix) pharmaceutical and therapeutic proteins, and (x) edible vaccines, etc. Multiple genes in transgenic crops can be useful in developing durable disease resistance and a broad insect-control spectrum and could lead to potential cost-saving advantages for farmers. The development of transgenic to produce high-value pharmaceuticals and the edible vaccine is also under progress, which requires much more research and development work before commercially viable products will be available. In addition, molecular-aided selection (MAS) is now routinely used to enhance the speed and precision of plant breeding. Newer technologies need to be developed and deployed for enhancing and sustaining agricultural productivity. There is a need to optimize the use of biotechnology in conjunction with conventional technologies to achieve higher productivity with fewer resources. Therefore, genetic modification/ engineering of crop plants assumes greater importance, which demands the development and adoption of newer technology for the genetic improvement of crops for increasing crop productivity.

Keywords: biotechnology, plant genetic engineering, genetically modified, biotic, abiotic, disease resistance

Procedia PDF Downloads 66

Authors: Álvaro Ramírez Vidal, Martín Muñoz Morales, Francisco Jesús Fernández Morales, Luis Rodríguez Romero, José Villaseñor Camacho, Javier Llanos López

Abstract:

In recent times, environmental problems have led to the extensive use of biological systems to solve them. Among the different types of biological systems, the use of plants such as aquatic macrophytes in constructed wetlands and terrestrial plant species for treating polluted soils and sludge has gained importance. Though the use of constructed wetlands for wastewater treatment is a well-researched domain, the slowness of pollutant degradation and high biomass production pose some challenges. Plants used in CW participate in different mechanisms for the capture and degradation of pollutants that also can retain some pharmaceutical and personal care products (PPCPs) that are very persistent in the environment. Thus, these systems present advantages in line with the guidelines published for the transition towards friendly and ecological procedures as they are environmentally friendly systems, consume low energy, or capture atmospheric CO₂. However, the use of CW presents some drawbacks, as the slowness of pollutant degradation or the production of important amounts of plant biomass, which need to be harvested and managed periodically. Taking this opportunity in mind, it is important to highlight that this residual biomass (of lignocellulosic nature) could be used as the feedstock for the generation of carbonaceous materials using thermochemical transformations such as slow pyrolysis or hydrothermal carbonization to produce high-value biomass-derived carbons through sustainable processes as adsorbents, catalysts…, thereby improving the circular carbon economy. Thus, this work carried out the analysis of some PPCPs commonly found in urban wastewater, as salicylic acid or ibuprofen, to evaluate the remediation carried out for the Phragmites Australis. Then, after the harvesting, this biomass can be used to synthesize electrodes through hydrothermal carbonization (HTC) and produce high-value biomass-derived carbons with electrocatalytic activity to remove heavy metals and persistent pollutants, promoting circular economy concepts. To do this, it was chosen biomass derived from the natural environment in high environmental risk as the Daimiel Wetlands National Park in the center of Spain, and the rest of the biomass developed in a CW specifically designed to remove pollutants. The research emphasizes the impact of the composition of the biomass waste and the synthetic parameters applied during HTC on the electrocatalytic activity. Additionally, this parameter can be related to the physicochemical properties, as porosity, surface functionalization, conductivity, and mass transfer of the electrodes lytic inks. Data revealed that carbon materials synthesized have good surface properties (good conductivities and high specific surface area) that enhance the electro-oxidants generated and promote the removal of PPCPs and the chemical oxygen demand of polluted waters.

Keywords: constructed wetlands, carbon materials, heavy metals, pharmaceutical and personal care products, hydrothermal carbonization

Procedia PDF Downloads 81

Authors: A. Boonpratatong, J. Pantong, S. Kiattisaksophon, W. Senavongse

Abstract:

In this study, an integrated sensing and modeling system for manual wheelchair propulsion measurement and propulsion efficiency calculation was used to indicate the level of overuse. Seven subjects participated in the measurement. On the level surface, the propulsion efficiencies were not different significantly as the riding speed increased. By contrast, the propulsion efficiencies on the 15-degree incline were restricted to around 0.5. The results are supported by previously reported wheeling resistance and propulsion torque relationships implying margin of the overuse. Upper limb musculoskeletal injuries and syndromes in manual wheelchair riders are common, chronic, and may be caused at different levels by the overuse i.e. repetitive riding on steep incline. The qualitative analysis such as the mechanical effectiveness on manual wheeling to establish the relationship between the riding difficulties, mechanical efforts and propulsion outputs is scarce, possibly due to the challenge of simultaneous measurement of those factors in conventional manual wheelchairs and everyday environments. In this study, the integrated sensing and modeling system were used to measure manual wheelchair propulsion efficiency in conventional manual wheelchairs and everyday environments. The sensing unit is comprised of the contact pressure and inertia sensors which are portable and universal. Four healthy male and three healthy female subjects participated in the measurement on level and 15-degree incline surface. Subjects were asked to perform manual wheelchair ridings with three different self-selected speeds on level surface and only preferred speed on the 15-degree incline. Five trials were performed in each condition. The kinematic data of the subject’s dominant hand and a spoke and the trunk of the wheelchair were collected through the inertia sensors. The compression force applied from the thumb of the dominant hand to the push rim was collected through the contact pressure sensors. The signals from all sensors were recorded synchronously. The subject-selected speeds for slow, preferred and fast riding on level surface and subject-preferred speed on 15-degree incline were recorded. The propulsion efficiency as a ratio between the pushing force in tangential direction to the push rim and the net force as a result of the three-dimensional riding motion were derived by inverse dynamic problem solving in the modeling unit. The intra-subject variability of the riding speed was not different significantly as the self-selected speed increased on the level surface. Since the riding speed on the 15-degree incline was difficult to regulate, the intra-subject variability was not applied. On the level surface, the propulsion efficiencies were not different significantly as the riding speed increased. However, the propulsion efficiencies on the 15-degree incline were restricted to around 0.5 for all subjects on their preferred speed. The results are supported by the previously reported relationship between the wheeling resistance and propulsion torque in which the wheelchair axle torque increased but the muscle activities were not increased when the resistance is high. This implies the margin of dynamic efforts on the relatively high resistance being similar to the margin of the overuse indicated by the restricted propulsion efficiency on the 15-degree incline.

Keywords: contact pressure sensor, inertia sensor, integrating sensing and modeling system, manual wheelchair propulsion efficiency, manual wheelchair propulsion measurement, tangential force, resultant force, three-dimensional riding motion

Procedia PDF Downloads 285

Authors: Huan Peng, Chenye Zeng, Zhao Wang

Abstract:

Alzheimer’s disease (AD) is an age-related neurodegenerative disease that is a leading cause of dementia syndromes and has become a huge burden on society and families. The main pathological features of AD involve excessive deposition of β-amyloid (Aβ) and Tau proteins in the brain, resulting in loss of neurons, expansion of neuroinflammation, and cognitive dysfunction in patients. Researchers have found effective drugs to clear the brain of error-accumulating proteins or to slow the loss of neurons, but their direct administration has key bottlenecks such as single-drug limitation, rapid blood clearance rate, impenetrable blood-brain barrier (BBB), and poor ability to target tissues and cells. Therefore, we are committed to seeking a suitable and efficient delivery system. Inspired by the possibility that exosomes may be involved in the secretion and transport mechanism of many signaling molecules or proteins in the brain, exosomes have attracted extensive attention as natural nanoscale drug carriers. We selected exosomes derived from bone marrow mesenchymal stem cells (MSC-EXO) with low immunogenicity and exosomes derived from hippocampal neurons (HT22-EXO) that may have excellent homing ability to overcome the deficiencies of oral or injectable pathways and bypass the BBB through nasal administration and evaluated their delivery ability and effect on AD. First, MSC-EXO and HT22 cells were isolated and cultured, and MSCs were identified by microimaging and flow cytometry. Then MSC-EXO and HT22-EXO were obtained by gradient centrifugation and qEV SEC separation column, and a series of physicochemical characterization were performed by transmission electron microscope, western blot, nanoparticle tracking analysis and dynamic light scattering. Next, exosomes labeled with lipophilic fluorescent dye were administered to WT mice and APP/PS1 mice to obtain fluorescence images of various organs at different times. Finally, APP/PS1 mice were administered intranasally with two exosomes 20 times over 40 days and 20 μL each time. Behavioral analysis and pathological section analysis of the hippocampus were performed after the experiment. The results showed that MSC-EXO and HT22-EXO were successfully isolated and characterized, and they had good biocompatibility. MSC-EXO showed excellent brain enrichment in APP/PS1 mice after intranasal administration, could improve the neuronal damage and reduce inflammation levels in the hippocampus of APP/PS1 mice, and the improvement effect was significantly better than HT22-EXO. However, intranasal administration of the two exosomes did not cause depression and anxious-like phenotypes in APP/PS1 mice, nor significantly improved the short-term or spatial learning and memory ability of APP/PS1 mice, and had no significant effect on the content of Aβ plaques in the hippocampus, which also meant that MSC-EXO could use their own advantages in combination with other drugs to clear Aβ plaques. The possibility of realizing highly effective non-invasive synergistic treatment for AD provides new strategies and ideas for clinical research.

Keywords: Alzheimer’s disease, exosomes derived from mesenchymal stem cell, intranasal administration, therapy-carrier dual roles

Procedia PDF Downloads 46

Authors: Daniela Stephanie Kuenstle

Abstract:

Complex industries such as banking or insurance experience slow growth in mobile sales. While today’s mobile applications are sophisticated and enable location based and personalized services, consumers prefer online or even face-to-face services to complete complex transactions. A possible reason for this reluctance is that the provided service within transactional mobile applications (apps) does not adequately correspond to users’ needs. Therefore, this paper examines the impact of the user context on mobile service (m-service) in m-commerce. Motivated by the potential which context-sensitive m-services hold for the future, the impact of temporal variations as a dimension of user context, on m-service design is examined. In particular, the research question asks: Does consumer urgency function as a determinant of m-service composition in transactional apps by moderating the relation between m-service type and m-service success? Thus, the aim is to explore the moderating influence of urgency on m-service types, which includes Technology Mediated Service and Technology Generated Service. While mobile applications generally comprise features of both service types, this thesis discusses whether unexpected urgency changes customer preferences for m-service types and how this consequently impacts the overall m-service success, represented by purchase intention, loyalty intention and service quality. An online experiment with a random sample of N=1311 participants was conducted. Participants were divided into four treatment groups varying in m-service types and urgency level. They were exposed to two different urgency scenarios (high/ low) and two different app versions conveying either technology mediated or technology generated service. Subsequently, participants completed a questionnaire to measure the effectiveness of the manipulation as well as the dependent variables. The research model was tested for direct and moderating effects of m-service type and urgency on m-service success. Three two-way analyses of variance confirmed the significance of main effects, but demonstrated no significant moderation of urgency on m-service types. The analysis of the gathered data did not confirm a moderating effect of urgency between m-service type and service success. Yet, the findings propose an additive effects model with the highest purchase and loyalty intention for Technology Generated Service and high urgency, while Technology Mediated Service and low urgency demonstrate the strongest effect for service quality. The results also indicate an antagonistic relation between service quality and purchase intention depending on the level of urgency. Although a confirmation of the significance of this finding is required, it suggests that only service convenience, as one dimension of mobile service quality, delivers conditional value under high urgency. This suggests a curvilinear pattern of service quality in e-commerce. Overall, the paper illustrates the complex interplay of technology, user variables, and service design. With this, it contributes to a finer-grained understanding of the relation between m-service design and situation dependency. Moreover, the importance of delivering situational value with apps depending on user context is emphasized. Finally, the present study raises the demand to continue researching the impact of situational variables on m-service design in order to develop more sophisticated m-services.

Keywords: mobile consumer behavior, mobile service design, mobile service success, self-service technology, situation dependency, user-context sensitivity

Procedia PDF Downloads 262

Authors: Nicki Mohammadi, Emma Reford, Natalia Romano Spica, Laura Tabacof, Jenna Tosto-Mancuso, David Putrino, Christopher P. Kellner

Abstract:

Introductory Statement: The onset of the COVID-19 pandemic demanded an unprecedented need for the rapid development, dispersal, and application of infection testing. However, despite the impressive mobilization of resources, individuals were incredibly limited in their access to tests, particularly during the initial months of the pandemic (March-April 2020) in New York City (NYC). Access to COVID-19 testing is crucial in understanding patients’ illness experiences and integral to the development of COVID-19 standard-of-care protocols, especially in the context of overall access to healthcare resources. Succinct Description of basic methodologies: 18 Patients in a COVID-19 Remote Patient Monitoring Program (Precision Recovery within the Mount Sinai Health System) were interviewed regarding their experience with COVID-19 during the first wave (March-May 2020) of the COVID-19 pandemic in New York City. Patients were asked about their experiences navigating COVID-19 diagnoses, the health care system, and their recovery process. Transcribed interviews were analyzed for thematic codes, using grounded theory to guide the identification of emergent themes and codebook development through an iterative process. Data coding was performed using NVivo12. References for the domain “testing” were then extracted and analyzed for themes and statistical patterns. Clear Indication of Major Findings of the study: 100% of participants (18/18) referenced COVID-19 testing in their interviews, with a total of 79 references across the 18 transcripts (average: 4.4 references/interview; 2.7% interview coverage). 89% of participants (16/18) discussed the difficulty of access to testing, including denial of testing without high severity of symptoms, geographical distance to the testing site, and lack of testing resources at healthcare centers. Participants shared varying perspectives on how the lack of certainty regarding their COVID-19 status affected their course of recovery. One participant shared that because she never tested positive she was shielded from her anxiety and fear, given the death toll in NYC. Another group of participants shared that not having a concrete status to share with family, friends and professionals affected how seriously onlookers took their symptoms. Furthermore, the absence of a positive test barred some individuals from access to treatment programs and employment support. Concluding Statement: Lack of access to COVID-19 testing in the first wave of the pandemic in NYC was a prominent element of patients’ illness experience, particularly during their recovery phase. While for some the lack of concrete results was protective, most emphasized the invalidating effect this had on the perception of illness for both self and others. COVID-19 testing is now widely accessible; however, those who are unable to demonstrate a positive test result but who are still presumed to have had COVID-19 in the first wave must continue to adapt to and live with the effects of this gap in knowledge and care on their recovery. Future efforts are required to ensure that patients do not face barriers to care due to the lack of testing and are reassured regarding their access to healthcare. Affiliations- 1Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 2Abilities Research Center, Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY

Keywords: accessibility, COVID-19, recovery, testing

Procedia PDF Downloads 187

Authors: Utpal Das, Sona Das

Abstract:

InAs/GaSb type-II superlattice (T2SL) Mid-wave infrared (MWIR) focal plane arrays (FPAs) have recently seen rapid development. However, in small pixel size large format FPAs, the occurrence of high mesa sidewall surface leakage current is a major constraint necessitating proper surface passivation. A simple pixel isolation technique in InAs/GaSb T2SL detector arrays without the conventional mesa etching has been proposed to isolate the pixels by forming a more resistive higher band gap material from the SL, in the inter-pixel region. Here, a single step femtosecond (fs) laser anneal of the T2SL structure of the inter-pixel T2SL regions, have been used to increase the band gap between the pixels by QW-intermixing and hence increase isolation between the pixels. The p-i-n photodiode structure used here consists of a 506nm, (10 monolayer {ML}) InAs:Si (1x10¹⁸cm⁻³)/(10ML) GaSb SL as the bottom n-contact layer grown on an n-type GaSb substrate. The undoped absorber layer consists of 1.3µm, (10ML)InAs/(10ML)GaSb SL. The top p-contact layer is a 63nm, (10ML)InAs:Be(1x10¹⁸cm⁻³)/(10ML)GaSb T2SL. In order to improve the carrier transport, a 126nm of graded doped (10ML)InAs/(10ML)GaSb SL layer was added between the absorber and each contact layers. A 775nm 150fs-laser at a fluence of ~6mJ/cm² is used to expose the array where the pixel regions are masked by a Ti(200nm)-Au(300nm) cap. Here, in the inter-pixel regions, the p+ layer have been reactive ion etched (RIE) using CH₄+H₂ chemistry and removed before fs-laser exposure. The fs-laser anneal isolation improvement in 200-400μm pixels due to spatially selective quantum well intermixing for a blue shift of ~70meV in the inter-pixel regions is confirmed by FTIR measurements. Dark currents are measured between two adjacent pixels with the Ti(200nm)-Au(300nm) caps used as contacts. The T2SL quality in the active photodiode regions masked by the Ti-Au cap is hardly affected and retains the original quality of the detector. Although, fs-laser anneal of p+ only etched p-i-n T2SL diodes show a reduction in the reverse dark current, no significant improvement in the full RIE-etched mesa structures is noticeable. Hence for a 128x128 array fabrication of 8μm square pixels and 10µm pitch, SU8 polymer isolation after RIE pixel delineation has been used. X-n+ row contacts and Y-p+ column contacts have been used to measure the optical response of the individual pixels. The photo-response of these 8μm and other 200μm pixels under a 2ns optical pulse excitation from an Optical-Parametric-Oscillator (OPO), shows a peak responsivity of ~0.03A/W and 0.2mA/W, respectively, at λ~3.7μm. Temporal response of this detector array is seen to have a fast response ~10ns followed typical slow decay with ringing, attributed to impedance mismatch of the connecting co-axial cables. In conclusion, response times of a few ns have been measured in 8µm pixels of a 128x128 array. Although fs-laser anneal has been found to be useful in increasing the inter-pixel isolation in InAs/GaSb T2SL arrays by QW inter-mixing, it has not been found to be suitable for passivation of full RIE etched mesa structures with vertical walls on InAs/GaSb T2SL.

Keywords: band-gap blue-shift, fs-laser-anneal, InAs/GaSb T2SL, Inter-pixel isolation, ns-Response, photodiode array

Procedia PDF Downloads 143

Authors: Frances Turner

Abstract:

Gloves are significant physical objects, being one of the oldest forms of dress. Glove culture is part of every facet of life; its extraordinary history encompasses practicality, and symbolism reflecting a wide range of social practices. The survival of not only the gloves but associated articles enables the possibility to analyse real lives, however so far this area has been largely neglected. Limited information is available to students, researchers, or those involved with the design and making of gloves. There are several museums and independent collectors in England that hold collections of gloves (some from as early as 16th century), machinery, tools, designs and patterns, marketing materials and significant archives which demonstrate the rich heritage of English glove design and manufacturing, being of national significance and worthy of international interest. Through a research glove network which now exists thanks to research grant funding, there is potential for the holders of glove collections to make connections and explore links between these resources to promote a stronger understanding of the significance, breadth and heritage of the English glove industry. The network takes an interdisciplinary approach to bring together interested parties from academia, museums and manufacturing, with expert knowledge of the production, collections, conservation and display of English leather gloves. Academics from diverse arts and humanities disciplines benefit from the opportunities to share research and discuss ideas with network members from non-academic contexts including museums and heritage organisations, industry, and contemporary designers. The fragmented collections when considered in entirety provide an overview of English glove making since earliest times and those who wore them. This paper makes connections and explores links between these resources to promote a stronger understanding of the significance, breadth and heritage of the English Glove industry. The following areas are explored: current content and status of the individual museum collections, potential links, sharing of information histories, social and cultural and relationship to history of fashion design, manufacturing and materials, approaches to maintenance and conservation, access to the collections and strategies for future understanding of their national significance. The facilitation of knowledge exchange and exploration of the collections through the network informs organisations’ future strategies for the maintenance, access and conservation of their collections. By involving industry in the network, it is possible to ensure a contemporary perspective on glove-making in addition to the input from heritage partners. The slow fashion movement and awareness of artisan craft and how these can be preserved and adopted for glove and accessory design is addressed. Artisan leather glove making was a skilled and significant industry in England that has now declined to the point where there is little production remaining utilising the specialist skills that have hardly changed since earliest times. This heritage will be identified and preserved for future generations of the rich cultural history of gloves may be lost.

Keywords: artisan glove-making skills, English leather gloves, glove culture, the glove network

Procedia PDF Downloads 119

Authors: Kakali Roy, Sahana P. Raju, Subhra Dhar, Sandipan Dhar

Abstract:

Introduction: Xeroderma pigmentosa (XP) is a rare inherited (autosomal recessive) disease resulting from impairment in DNA repair that involves recognition and repair of ultraviolet radiation (UVR) induced DNA damage in the nucleotide excision repair pathway. Which results in increased photosensitivity, UVR induced damage to skin and eye, increased susceptibility of skin and ocular cancer, and progressive neurodegeneration in some patients. XP is present worldwide, with higher incidence in areas having frequent consanguinity. Being extremely rare, there is limited literature on XP and associated complications. Here, the clinico-pathological experience (spectrum of clinical presentation, histopathological findings of malignant skin lesions, and progression) of managing 8 cases of XP is presented. Methodology: A retrospective study was conducted in a pediatric tertiary care hospital in eastern India during a ten-year period from 2013 to 2022. A clinical diagnosis was made based on severe sun burn or premature photo-aging and/or onset of cutaneous malignancies at early age (1st decade) in background of consanguinity and autosomal recessive inheritance pattern in family. Results: The mean age of presentation was 1.2 years (range of 7month-3years), while three children presented during their infancy. Male to female ratio was 5:3, and all were born of consanguineous marriage. They presented with dermatological manifestations (100%) followed by ophthalmic (75%) and/or neurological symptoms (25%). Patients had normal skin at birth but soon developed extreme sensitivity to UVR in the form of exaggerated sun tanning, burning, and blistering on minimal sun exposure, followed by abnormal skin pigmentation like freckles and lentiginosis. Subsequently, over time there was progressive xerosis, atrophy, wrinkling, and poikiloderma. Six patients had varied degree of ocular involvement, while three of them had severe manifestation, including madarosis, tylosis, ectropion, Lagopthalmos, Pthysis bulbi, clouding and scarring of the cornea with complete or partial loss of vision, and ophthalmic malignancies. 50% (n=4) cases had skin and ocular pre-malignant (actinic keratosis) and malignant lesions, including melanoma and non melanoma skin cancer (NMSC) like squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in their early childhood. One patient had simultaneous occurrence of multiple malignancies together (SCC, BCC, and melanoma). Subnormal intelligence was noticed as neurological feature, and none had sensory neural hearing loss, microcephaly, neuroregression, or neurdeficit. All the patients had been being managed by a multidisciplinary team of pediatricians, dermatologists, ophthalmologists, neurologists and psychiatrists. Conclusion: Although till date there is no complete cure for XP and the disease is ultimately fatal. But increased awareness, early diagnosis followed by persistent vigorous protection from UVR, and regular screening for early detection of malignancies along with psychological support can drastically improve patients’ quality of life and life expectancy. Further research is required on formulating optimal management of XP, specifically the role and possibilities of gene therapy in XP.

Keywords: childhood malignancies, dermato-pathological findings, eastern India, Xeroderma pigmentosa

Procedia PDF Downloads 69

Authors: Lise Paesen, Marielle Leijten

Abstract:

People diagnosed with probable Alzheimer disease suffer from an impairment of their language capacities; a gradual impairment which affects both their spoken and written communication. Our study aims at characterising the language decline in DAT patients with the use of congeneric elicited writing tasks. Within these tasks, a descriptive text has to be written based upon images with which the participants are confronted. A randomised set of images allows us to present the participants with a different task on every encounter, thus allowing us to avoid a recognition effect in this iterative study. This method is a revision from previous studies, in which participants were presented with a larger picture depicting an entire scene. In order to create the randomised set of images, existing pictures were adapted following strict criteria (e.g. frequency, AoA, colour, ...). The resulting data set contained 50 images, belonging to several categories (vehicles, animals, humans, and objects). A pre-test was constructed to validate the created picture set; most images had been used before in spoken picture naming tasks. Hence the same reaction times ought to be triggered in the typed picture naming task. Once validated, the effectiveness of the descriptive tasks was assessed. First, the participants (n=60 students, n=40 healthy elderly) performed a typing task, which provided information about the typing speed of each individual. Secondly, two descriptive writing tasks were carried out, one simple and one complex. The simple task contains 4 images (1 animal, 2 objects, 1 vehicle) and only contains elements with high frequency, a young AoA (<6 years), and fast reaction times. Slow reaction times, a later AoA (≥ 6 years) and low frequency were criteria for the complex task. This task uses 6 images (2 animals, 1 human, 2 objects and 1 vehicle). The data were collected with the keystroke logging programme Inputlog. Keystroke logging tools log and time stamp keystroke activity to reconstruct and describe text production processes. The data were analysed using a selection of writing process and product variables, such as general writing process measures, detailed pause analysis, linguistic analysis, and text length. As a covariate, the intrapersonal interkey transition times from the typing task were taken into account. The pre-test indicated that the new images lead to similar or even faster reaction times compared to the original images. All the images were therefore used in the main study. The produced texts of the description tasks were significantly longer compared to previous studies, providing sufficient text and process data for analyses. Preliminary analysis shows that the amount of words produced differed significantly between the healthy elderly and the students, as did the mean length of production bursts, even though both groups needed the same time to produce their texts. However, the elderly took significantly more time to produce the complex task than the simple task. Nevertheless, the amount of words per minute remained comparable between simple and complex. The pauses within and before words varied, even when taking personal typing abilities (obtained by the typing task) into account.

Keywords: Alzheimer's disease, experimental design, language decline, writing process

Procedia PDF Downloads 267

Authors: Beverly Redman

Abstract:

With the Theatre Season of 2020-2021 cancelled due to COVID-19 at Purdue University, Fort Wayne, IN, USA, faculty directors found themselves scrambling to create theatre production opportunities for their students in the Department of Theatre. Redman, Chair of the Department, found her community to be suffering from anxieties brought on by a confluence of issues: the global-scale Covid-19 Pandemic, the United States’ Black Lives Matter protests erupting in cities all across the country and the coming Presidential election, arguably the most important and most contentious in the country’s history. Redman wanted to give her students the opportunity to speak not only on these issues but also to be able to record who they were at this time in their personal lives, as well as in this broad socio-political context. She also wanted to invite them into an experience of feeling empathy, too, at a time when empathy in this world seems to be sorely lacking. Returning to a mode of Devising Theatre she had used with community groups in the past, in which storytelling and re-enactment of participants’ life events combined with oral history documentation practices, Redman planned The Shared Breath Project. The process involved three months of workshops, in which participants alternated between theatre exercises and oral history collection and documentation activities as a way of generating original material for a theatre production. The goal of the first half of the project was for each participant to produce a solo piece in the form of a monologue after many generations of potential material born out of gammes, improvisations, interviews and the like. Along the way, many film and audio clips recorded the process of each person’s written documentation—documentation prepared by the subject him or herself but also by others in the group assigned to listen, watch and record. Then, in the second half of the project—and only once each participant had taken their own contributions from raw improvisatory self-presentations and through the stages of composition and performative polish, participants then exchanged their pieces. The second half of the project involved taking on each other’s words, mannerisms, gestures, melodic and rhythmic speech patterns and inhabiting them through the rehearsal process as their own, thus the title, The Shared Breath Project. Here, in stage two the acting challenges evolved to be those of capturing the other and becoming the other through accurate mimicry that embraces Denis Diderot’s concept of the Paradox of Acting, in that the actor is both seeming and being simultaneous. This paper shares the carefully documented process of making the live-streamed theatre production that resulted from these workshops, writing processes and rehearsals, and forming, The Shared Breath Project, which ultimately took the students’ Realist, life-based pieces and edited them into a single unified theatre production. The paper also utilizes research on the Paradox of Acting, putting a Post-Structuralist spin on Diderot’s theory. Here, the paper suggests the limitations of inhabiting the other by allowing that the other is always already a thing impenetrable but nevertheless worthy of unceasing empathetic, striving and delving in an epoch in which slow, careful attention to our fellows is in short supply.

Keywords: otherness, paradox of acting, oral history theatre, devised theatre, political theatre, community-based theatre, peoples’ theatre

Procedia PDF Downloads 178

Authors: Mikaela Kutrolli, Noah S. Pereira, Vanessa Scanlon, Mohamadmahdi Samandari, Ali Tamayol

Abstract:

Bone tissue engineering has drawn significant attention and various biomaterials have been tested. Polymers such as polycaprolactone (PCL) offer excellent biocompatibility, reasonable mechanical properties, and biodegradability. However, PCL scaffolds suffer a critical drawback: a lack of micro/mesoporosity, affecting cell attachment, tissue integration, and mineralization. It also results in a slow degradation rate. While 3D-printing has addressed the issue of macroporosity through CAD-guided fabrication, PCL scaffolds still exhibit poor smaller-scale porosity. To overcome this, we generated composites of PCL, hydroxyapatite (HA), and powdered sucrose (PS). The latter serves as a sacrificial material to generate porous particles after sucrose dissolution. Additionally, we have incorporated dexamethasone (DEX) to boost the PCL osteogenic properties. The resulting scaffolds maintain controlled macroporosity from the lattice print structure but also develop micro/mesoporosity within PCL fibers when exposed to aqueous environments. The study involved mixing PS into solvent-dissolved PCL in different weight ratios of PS to PCL (70:30, 50:50, and 30:70 wt%). The resulting composite was used for 3D printing of scaffolds at room temperature. Printability was optimized by adjusting pressure, speed, and layer height through filament collapse and fusion test. Enzymatic degradation, porogen leaching, and DEX release profiles were characterized. Physical properties were assessed using wettability, SEM, and micro-CT to quantify the porosity (percentage, pore size, and interconnectivity). Raman spectroscopy was used to verify the absence of sugar after leaching. Mechanical characteristics were evaluated via compression testing before and after porogen leaching. Bone marrow stromal cells (BMSCs) behavior in the printed scaffolds was studied by assessing viability, metabolic activity, osteo-differentiation, and mineralization. The scaffolds with a 70% sugar concentration exhibited superior printability and reached the highest porosity of 80%, but performed poorly during mechanical testing. A 50% PS concentration demonstrated a 70% porosity, with an average pore size of 25 µm, favoring cell attachment. No trace of sucrose was found in Raman after leaching the sugar for 8 hours. Water contact angle results show improved hydrophilicity as the sugar concentration increased, making the scaffolds more conductive to cell adhesion. The behavior of bone marrow stromal cells (BMSCs) showed positive viability and proliferation results with an increasing trend of mineralization and osteo-differentiation as the sucrose concentration increased. The addition of HA and DEX also promoted mineralization and osteo-differentiation in the cultures. The integration of PS as porogen at a concentration of 50%wt within PCL scaffolds presents a promising approach to address the poor cell attachment and tissue integration issues of PCL in bone tissue engineering. The method allows for the fabrication of scaffolds with tunable porosity and mechanical properties, suitable for various applications. The addition of HA and DEX further enhanced the scaffolds. Future studies will apply the scaffolds in an in-vivo model to thoroughly investigate their performance.

Keywords: bone, PCL, 3D printing, tissue engineering

Procedia PDF Downloads 43

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

Abstract:

Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

Procedia PDF Downloads 344

Authors: Ankita Baidya, Vanishri Ganakumar, Ranveer S. Jadon, Piyush Ranjan, Rita Sood

Abstract:

Septic embolism can have varied presentations and clinical considerations. Infected central venous catheters are commonly associated with septic emboli but peripheral vascular catheters are rarely implicated. We describe a rare case of septic pulmonary emboli related to infected peripheral venous cannulation caused by an unusual etiological agent. A young male presented with complaints of fever, productive cough, sudden onset shortness of breath and cellulitis in both the upper limbs. He was recently hospitalised for dengue fever and administered intravenous fluids through peripheral venous line. The patient was febrile, tachypneic and in respiratory distress, there were multiple pus filled bullae in left hand alongwith swelling and erythema involving right forearm that started at the site of cannulation. Chest examination showed active accessory muscles of respiration, stony dull percussion at the base of right lung and decreased breath sounds at right infrascapular, infraaxillary and mammary area. Other system examination was within normal limits. Chest X-ray revealed bilateral multiple patchy heterogenous peripheral opacities and infiltrates with right-sided pleural effusion. Contrast-enhanced computed tomography (CECT) chest showed feeding vessel sign confirming the diagnosis as septic emboli. Venous Doppler and 2D-echocardiogarm were normal. Laboratory findings showed marked leucocytosis (22000/mm3). Pus aspirate, blood sample, and sputum sample were sent for microbiological testing. The patient was started empirically on ceftriaxone, vancomycin, and clindamycin. The Pus culture and sputum culture showed Klebsiella pneumoniae sensitive to cefoperazone-sulbactum, piperacillin-tazobactum, meropenem and amikacin. The antibiotics were modified accordingly to antimicrobial sensitivity profile to Cefoperazone-sulbactum. Bronchoalveolar lavage (BAL) was done and sent for microbiological investigations. BAL culture showed Klebsiella pneumoniae with same antimicrobial resistance profile. On day 6 of starting cefoperazone-sulbactum, he became afebrile. The skin lesions improved significantly. He was administered 2 weeks of cefoperazone–sulbactum and discharged on oral faropenem for 4 weeks. At the time of discharge, TLC was 11200/mm3 with marked radiological resolution of infection and healed skin lesions. He was kept in regular follow up. Chest X-ray and skin lesions showed complete resolution after 8 weeks. Till date, only couple of case reports of septic emboli through peripheral intravenous line have been reported in English literature. This case highlights that a simple procedure of peripheral intravenous cannulation can lead to catastrophic complication of septic pulmonary emboli and widespread cellulitis if not done with proper care and precautions. Also, the usual pathogens in such clinical settings are gram positive bacteria, but with the history of recent hospitalization, empirical therapy should also cover drug resistant gram negative microorganisms. It also emphasise the importance of appropriate healthcare practices to be taken care during all procedures.

Keywords: antibiotics, cannula, Klebsiella pneumoniae, septic emboli

Procedia PDF Downloads 152

Authors: Siyamak Ziyaei, Siti Khalijah Mazlan, Petros Lappas

Abstract:

Compressed Natural Gas (CNG) mainly consists of Methane CH₄ and has a low carbon to hydrogen ratio relative to other hydrocarbons. As a result, it has the potential to reduce CO₂ emissions by more than 20% relative to conventional fuels like diesel or gasoline Although Natural Gas (NG) has environmental advantages compared to other hydrocarbon fuels whether they are gaseous or liquid, its main component, CH₄, burns at a slower rate than conventional fuels A higher pressure and a leaner cylinder environment will overemphasize slow burn characteristic of CH₄. Lean combustion and high compression ratios are well-known methods for increasing the efficiency of internal combustion engines. In order to achieve successful CNG lean combustion in Spark Ignition (SI) engines, a strong ignition system is essential to avoid engine misfires, especially in ultra-lean conditions. Turbulent Jet Ignition (TJI) is an ignition system that employs a pre-combustion chamber to ignite the lean fuel mixture in the main combustion chamber using a fraction of the total fuel per cycle. TJI enables ultra-lean combustion by providing distributed ignition sites through orifices. The fast burn rate provided by TJI enables the ordinary SI engine to be comparable to other combustion systems such as Homogeneous Charge Compression Ignition (HCCI) or Controlled Auto-Ignition (CAI) in terms of thermal efficiency, through the increased levels of dilution without the need of sophisticated control systems. Due to the physical geometry of TJIs, which contain small orifices that connect the prechamber to the main chamber, scavenging is one of the main factors that reduce TJI performance. Specifically, providing the right mixture of fuel and air has been identified as a key challenge. The reason for this is the insufficient amount of air that is pushed into the pre-chamber during each compression stroke. There is also the problem that combustion residual gases such as CO₂, CO and NOx from the previous combustion cycle dilute the pre- chamber fuel-air mixture preventing rapid combustion in the pre-chamber. An air-controlled active TJI is presented in this paper in order to address these issues. By applying air to the pre-chamber at a sufficient pressure, residual gases are exhausted, and the air-fuel ratio is controlled within the pre-chamber, thereby improving the quality of combustion. This paper investigates the 3D-simulated combustion characteristics of a Direct Injected (DI-CNG) fuelled SI en- gine with a pre-chamber equipped with an air channel by using AVL FIRE software. Experiments and simulations were performed at the Worldwide Mapping Point (WWMP) at 1500 Revolutions Per Minute (RPM), 3.3 bar Indicated Mean Effective Pressure (IMEP), using only conventional spark plugs as the baseline. After validating simulation data, baseline engine conditions were set for all simulation scenarios at λ=1. Following that, the pre-chambers with and without an auxiliary fuel supply were simulated. In the simulated (DI-CNG) SI engine, active TJI was observed to perform better than passive TJI and spark plug. In conclusion, the active pre-chamber with an air channel demon-strated an improved thermal efficiency (ηth) over other counterparts and conventional spark ignition systems.

Keywords: turbulent jet ignition, active air control turbulent jet ignition, pre-chamber ignition system, active and passive pre-chamber, thermal efficiency, methane combustion, internal combustion engine combustion emissions

Procedia PDF Downloads 79