Search results for: disease modeling

Authors: E. Omanya, E. Mueni, G. Makau, M. Kariuki

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HIV infection is the strongest risk factor for a person to develop TB. Isoniazid preventive therapy (IPT) for People Living with HIV (PLWHIV) not only reduces the individual patients’ risk of developing active TB but mitigates cross infection. In Kenya, IPT for six months was recommended through the National TB, Leprosy and Lung Disease Program to treat latent TB. In spite of this recommendation by the national government, uptake of IPT among PLHIV remained low in Kenya by the end of 2015. The USAID/Kenya and East Africa Afya Jijini project, which supports 42 TBHIV health facilities in Nairobi County, began addressing low uptake of IPT through Quality Improvement (QI) teams set up at the facility level. Quality is characterized by WHO as one of the four main connectors between health systems building blocks and health systems outputs. Afya Jijini implements the Kenya Quality Model for Health, which involves QI teams being formed at the county, sub-county and facility levels. The teams review facility performance to identify gaps in service delivery and use QI tools to monitor and improve performance. Afya Jijini supported the formation of these teams in 42 facilities and built the teams’ capacity to review data and use QI principles to identify and address performance gaps. When the QI teams began working on improving IPT uptake among PLHIV, uptake was at 31.8%. The teams first conducted a root cause analysis using cause and effect diagrams, which help the teams to brainstorm on and to identify barriers to IPT uptake among PLHIV at the facility level. This is a participatory process where program staff provides technical support to the QI teams in problem identification and problem-solving. The gaps identified were inadequate knowledge and skills on the use of IPT among health care workers, lack of awareness of IPT by patients, inadequate monitoring and evaluation tools, and poor quantification and forecasting of IPT commodities. In response, Afya Jijini trained over 300 health care workers on the administration of IPT, supported patient education, supported quantification and forecasting of IPT commodities, and provided IPT data collection tools to help facilities monitor their performance. The facility QI teams conducted monthly meetings to monitor progress on implementation of IPT and took corrective action when necessary. IPT uptake improved from 31.8% to 61.2% during the second year of the Afya Jijini project and improved to 80.1% during the third year of the project’s support. Use of QI teams and root cause analysis to identify and address service delivery gaps, in addition to targeted program interventions and continual performance reviews, can be successful in increasing TB related service delivery uptake at health facilities.

Keywords: isoniazid, quality, health care workers, people leaving with HIV

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Authors: Wedad Albalawi

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The mathematical inequalities have been the core of mathematical study and used in almost all branches of mathematics as well in various areas of science and engineering. The inequalities by Hardy, Littlewood and Polya were the first significant composition of several science. This work presents fundamental ideas, results and techniques, and it has had much influence on research in various branches of analysis. Since 1934, various inequalities have been produced and studied in the literature. Furthermore, some inequalities have been formulated by some operators; in 1989, weighted Hardy inequalities have been obtained for integration operators. Then, they obtained weighted estimates for Steklov operators that were used in the solution of the Cauchy problem for the wave equation. They were improved upon in 2011 to include the boundedness of integral operators from the weighted Sobolev space to the weighted Lebesgue space. Some inequalities have been demonstrated and improved using the Hardy–Steklov operator. Recently, a lot of integral inequalities have been improved by differential operators. Hardy inequality has been one of the tools that is used to consider integrity solutions of differential equations. Then, dynamic inequalities of Hardy and Coposon have been extended and improved by various integral operators. These inequalities would be interesting to apply in different fields of mathematics (functional spaces, partial differential equations, mathematical modeling). Some inequalities have been appeared involving Copson and Hardy inequalities on time scales to obtain new special version of them. A time scale is an arbitrary nonempty closed subset of the real numbers. Then, the dynamic inequalities on time scales have received a lot of attention in the literature and has become a major field in pure and applied mathematics. There are many applications of dynamic equations on time scales to quantum mechanics, electrical engineering, neural networks, heat transfer, combinatorics, and population dynamics. This study focuses on Hardy and Coposon inequalities, using Steklov operator on time scale in double integrals to obtain special cases of time-scale inequalities of Hardy and Copson on high dimensions. The advantage of this study is that it uses the one-dimensional classical Hardy inequality to obtain higher dimensional on time scale versions that will be applied in the solution of the Cauchy problem for the wave equation. In addition, the obtained inequalities have various applications involving discontinuous domains such as bug populations, phytoremediation of metals, wound healing, maximization problems. The proof can be done by introducing restriction on the operator in several cases. The concepts in time scale version such as time scales calculus will be used that allows to unify and extend many problems from the theories of differential and of difference equations. In addition, using chain rule, and some properties of multiple integrals on time scales, some theorems of Fubini and the inequality of H¨older.

Keywords: time scales, inequality of hardy, inequality of coposon, steklov operator

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Authors: Hui-Ling Yang, Kuei-Ru Chou

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Background: Studies show that cognitive training can effectively delay cognitive failure. However, there are several gaps in the previous studies of cognitive training in mild cognitive impairment: 1) previous studies enrolled mostly healthy older adults, with few recruiting older adults with cognitive impairment; 2) they also had limited generalizability and lacked long-term follow-up data and measurements of the activities of daily living functional impact. Moreover, only 37% were randomized controlled trials (RCT). 3) Limited cognitive training has been specifically developed for mild cognitive impairment. Objective: This study sought to investigate the changes in cognitive function, activities of daily living and degree of depressive symptoms in older adults with mild cognitive impairment after cognitive training. Methods: This double-blind randomized controlled study has a 2-arm parallel group design. Study subjects are older adults diagnosed with mild cognitive impairment in residential care facilities. 124 subjects will be randomized by the permuted block randomization, into intervention group (Cognitive training, CT), or active control group (Passive information activities, PIA). Therapeutic adherence, sample attrition rate, medication compliance and adverse events will be monitored during the study period, and missing data analyzed using intent-to-treat analysis (ITT). Results: Training sessions of the CT group are 45 minutes/day, 3 days/week, for 12 weeks (36 sessions each). The training of active control group is the same as CT group (45min/day, 3days/week, for 12 weeks, for a total of 36 sessions). The primary outcome is cognitive function, using the Mini-Mental Status Examination (MMSE); the secondary outcome indicators are: 1) activities of daily living, using the Lawton’s Instrumental Activities of Daily Living (IADLs) and 2) degree of depressive symptoms, using the Geriatric Depression Scale-Short form (GDS-SF). Latent growth curve modeling will be used in the repeated measures statistical analysis to estimate the trajectory of improvement by examining the rate and pattern of change in cognitive functions, activities of daily living and degree of depressive symptoms for intervention efficacy over time, and the effects will be evaluated immediate post-test, 3 months, 6 months and one year after the last session. Conclusions: We constructed a rigorous CT program adhering to the Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines. We expect to determine the improvement in cognitive function, activities of daily living and degree of depressive symptoms of older adults with mild cognitive impairment after using the CT.

Keywords: mild cognitive impairment, cognitive training, randomized controlled study

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Authors: Benjamin Castillo, Luis Pastenes, Fernando Cerdova

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The contamination of food by microbial agents is a common problem in the industry, especially regarding the elaboration of animal source products. Incorrect manipulation of the machinery or on the raw materials can cause a decrease in production or an epidemiological outbreak due to intoxication. In order to improve food product quality, different methods have been used to reduce or, at least, to slow down the growth of the pathogens, especially deteriorated, infectious or toxigenic bacteria. These methods are usually carried out under low temperatures and short processing time (abiotic agents), along with the application of antibacterial substances, such as bacteriocins (biotic agents). This, in a controlled and efficient way that fulfills the purpose of bacterial control without damaging the final product. Therefore, the objective of the present study is to design a secondary mathematical model that allows the prediction of both the biotic and abiotic factor impact associated with animal source food processing. In order to accomplish this objective, the authors propose a three-dimensional differential equation model, whose components are: bacterial growth, release, production and artificial incorporation of bacteriocins and changes in pH levels of the medium. These three dimensions are constantly being influenced by the temperature of the medium. Secondly, this model adapts to an idealized situation of cross-contamination animal source food processing, with the study agents being both the animal product and the contact surface. Thirdly, the stochastic simulations and the parametric sensibility analysis are compared with referential data. The main results obtained from the analysis and simulations of the mathematical model were to discover that, although bacterial growth can be stopped in lower temperatures, even lower ones are needed to eradicate it. However, this can be not only expensive, but counterproductive as well in terms of the quality of the raw materials and, on the other hand, higher temperatures accelerate bacterial growth. In other aspects, the use and efficiency of bacteriocins are an effective alternative in the short and medium terms. Moreover, an indicator of bacterial growth is a low-level pH, since lots of deteriorating bacteria are lactic acids. Lastly, the processing times are a secondary agent of concern when the rest of the aforementioned agents are under control. Our main conclusion is that when acclimating a mathematical model within the context of the industrial process, it can generate new tools that predict bacterial contamination, the impact of bacterial inhibition, and processing method times. In addition, the mathematical modeling proposed logistic input of broad application, which can be replicated on non-meat food products, other pathogens or even on contamination by crossed contact of allergen foods.

Keywords: bacteriocins, cross-contamination, mathematical model, temperature

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Authors: Mohammad Bagher Anvari, Arman Shojaei

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Incremental launching, a widely adopted bridge erection technique, offers numerous advantages for bridge designers. However, accurately simulating and modeling the dynamic behavior of the bridge during each step of the launching process proves to be tedious and time-consuming. The perpetual variation of internal forces within the deck during construction stages adds complexity, exacerbated further by considerations of other load cases, such as support settlements and temperature effects. As a result, there is an urgent need for a reliable, simple, economical, and fast algorithmic solution to model bridge construction stages effectively. This paper presents a novel Finite Element (FE) model that focuses on studying the static behavior of bridges during the launching process. Additionally, a simple method is introduced to normalize all quantities in the problem. The new FE model overcomes the limitations of previous models, enabling the simulation of all stages of launching, which conventional models fail to achieve due to underlying assumptions. By leveraging the results obtained from the new FE model, this study proposes solutions to improve the accuracy of conventional models, particularly for the initial stages of bridge construction that have been neglected in previous research. The research highlights the critical role played by the first span of the bridge during the initial stages, a factor often overlooked in existing studies. Furthermore, a new and simplified model termed the "semi-infinite beam" model, is developed to address this oversight. By utilizing this model alongside a simple optimization approach, optimal values for launching nose specifications are derived. The practical applications of this study extend to optimizing the nose-deck system of incrementally launched bridges, providing valuable insights for practical usage. In conclusion, this paper introduces a comprehensive Finite Element model for studying the static behavior of bridges during incremental launching. The proposed model addresses limitations found in previous approaches and offers practical solutions to enhance accuracy. The study emphasizes the importance of considering the initial stages and introduces the "semi-infinite beam" model. Through the developed model and optimization approach, optimal specifications for launching nose configurations are determined. This research holds significant practical implications and contributes to the optimization of incrementally launched bridges, benefiting both the construction industry and bridge designers.

Keywords: incremental launching, bridge construction, finite element model, optimization

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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Authors: Antonio Pratelli, Lorenzo Brocchini, Reginald Roy Souleyrette

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A rotary is a traffic circle intersection where vehicles entering from branches give priority to circulating flow. Vehicles entering the intersection from converging roads move around the central island and weave out of the circle into their desired exiting branch. This creates merging and diverging conflicts among any entry and its successive exit, i.e., a section. Therefore, rotary capacity models are usually based on the weaving of the different movements in any section of the circle, and the maximum rate of flow value is then related to each weaving section of the rotary. Nevertheless, the single-section capacity value does not lead to the typical performance characteristics of the intersection, such as the entry average delay which is directly linked to its level of service. From another point of view, modern roundabout capacity models are based on the limitation of the flow entering from the single entrance due to the amount of flow circulating in front of the entrance itself. Modern roundabouts capacity models generally lead also to a performance evaluation. This paper aims to incorporate a modern roundabout capacity model into an old rotary capacity method to obtain from the latter the single input capacity and ultimately achieve the related performance indicators. Put simply; the main objective is to calculate the average delay of each single roundabout entrance to apply the most common Highway Capacity Manual, or HCM, criteria. The paper is organized as follows: firstly, the rotary and roundabout capacity models are sketched, and it has made a brief introduction to the model combination technique with some practical instances. The successive section is deserved to summarize the TRRL old rotary capacity model and the most recent HCM-7th modern roundabout capacity model. Then, the two models are combined through an iteration-based algorithm, especially set-up and linked to the concept of roundabout total capacity, i.e., the value reached due to a traffic flow pattern leading to the simultaneous congestion of all roundabout entrances. The solution is the average delay for each entrance of the rotary, by which is estimated its respective level of service. In view of further experimental applications, at this research stage, a collection of existing rotary intersections operating with the priority-to-circle rule has already started, both in the US and in Italy. The rotaries have been selected by direct inspection of aerial photos through a map viewer, namely Google Earth. Each instance has been recorded by location, general urban or rural, and its main geometrical patterns. Finally, conclusion remarks are drawn, and a discussion on some further research developments has opened.

Keywords: mixed methods, old rotary and modern roundabout capacity models, total capacity algorithm, level of service estimation

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Authors: Despina Giannadaki, Jos Lelieveld, Andrea Pozzer, John Evans

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Outdoor air pollution by fine particles ranks among the top ten global health risk factors that can lead to premature mortality. Epidemiological cohort studies, mainly conducted in United States and Europe, have shown that the long-term exposure to PM2.5 (particles with an aerodynamic diameter less than 2.5μm) is associated with increased mortality from cardiovascular, respiratory diseases and lung cancer. Fine particulates can cause health impacts even at very low concentrations. Previously, no concentration level has been defined below which health damage can be fully prevented. The World Health Organization ambient air quality guidelines suggest an annual mean PM2.5 concentration limit of 10μg/m3. Populations in large parts of the world, especially in East and Southeast Asia, and in the Middle East, are exposed to high levels of fine particulate pollution that by far exceeds the World Health Organization guidelines. The aim of this work is to evaluate the implementation of recent air quality standards for PM2.5 in the EU, the US and other countries worldwide and estimate what measures will be needed to substantially reduce premature mortality. We investigated premature mortality attributed to fine particulate matter (PM2.5) under adults ≥ 30yrs and children < 5yrs, applying a high-resolution global atmospheric chemistry model combined with epidemiological concentration-response functions. The latter are based on the methodology of the Global Burden of Disease for 2010, assuming a ‘safe’ annual mean PM2.5 threshold of 7.3μg/m3. We estimate the global premature mortality by PM2.5 at 3.15 million/year in 2010. China is the leading country with about 1.33 million, followed by India with 575 thousand and Pakistan with 105 thousand. For the European Union (EU) we estimate 173 thousand and the United States (US) 52 thousand in 2010. Based on sensitivity calculations we tested the gains from PM2.5 control by applying the air quality guidelines (AQG) and standards of the World Health Organization (WHO), the EU, the US and other countries. To estimate potential reductions in mortality rates we take into consideration the deaths that cannot be avoided after the implementation of PM2.5 upper limits, due to the contribution of natural sources to total PM2.5 and therefore to mortality (mainly airborne desert dust). The annual mean EU limit of 25μg/m3 would reduce global premature mortality by 18%, while within the EU the effect is negligible, indicating that the standard is largely met and that stricter limits are needed. The new US standard of 12μg/m3 would reduce premature mortality by 46% worldwide, 4% in the US and 20% in the EU. Implementing the AQG by the WHO of 10μg/m3 would reduce global premature mortality by 54%, 76% in China and 59% in India. In the EU and US, the mortality would be reduced by 36% and 14%, respectively. Hence, following the WHO guideline will prevent 1.7 million premature deaths per year. Sensitivity calculations indicate that even small changes at the lower PM2.5 standards can have major impacts on global mortality rates.

Keywords: air quality guidelines, outdoor air pollution, particulate matter, premature mortality

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Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab

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Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.

Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM

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Authors: Dino Carpentras, Paul J. Maher, Caoimhe O'Reilly, Michael Quayle

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Opinion dynamics is a sub-field of agent-based modeling that focuses on people’s opinions and their evolutions over time. Despite the rapid increase in the number of publications in this field, it is still not clear how to apply these models to real-world scenarios. Indeed, there is no agreement on how people update their opinion while interacting. Furthermore, it is not clear if different topics will show the same dynamics (e.g., more polarized topics may behave differently). These problems are mostly due to the lack of experimental validation of the models. Some previous studies started bridging this gap in the literature by directly measuring people’s opinions before and after the interaction. However, these experiments force people to express their opinion as a number instead of using natural language (and then, eventually, encoding it as numbers). This is not the way people normally interact, and it may strongly alter the measured dynamics. Another limitation of these studies is that they usually average all the topics together, without checking if different topics may show different dynamics. In our work, we collected data from 200 participants on 5 unpolarized topics. Participants expressed their opinions in natural language (“agree” or “disagree”). We also measured the certainty of their answer, expressed as a number between 1 and 10. However, this value was not shown to other participants to keep the interaction based on natural language. We then showed the opinion (and not the certainty) of another participant and, after a distraction task, we repeated the measurement. To make the data compatible with opinion dynamics models, we multiplied opinion and certainty to obtain a new parameter (here called “continuous opinion”) ranging from -10 to +10 (using agree=1 and disagree=-1). We firstly checked the 5 topics individually, finding that all of them behaved in a similar way despite having different initial opinions distributions. This suggested that the same model could be applied for different unpolarized topics. We also observed that people tend to maintain similar levels of certainty, even when they changed their opinion. This is a strong violation of what is suggested from common models, where people starting at, for example, +8, will first move towards 0 instead of directly jumping to -8. We also observed social influence, meaning that people exposed with “agree” were more likely to move to higher levels of continuous opinion, while people exposed with “disagree” were more likely to move to lower levels. However, we also observed that the effect of influence was smaller than the effect of random fluctuations. Also, this configuration is different from standard models, where noise, when present, is usually much smaller than the effect of social influence. Starting from this, we built an opinion dynamics model that explains more than 80% of data variance. This model was also able to show the natural conversion of polarization from unpolarized states. This experimental approach offers a new way to build models grounded on experimental data. Furthermore, the model offers new insight into the fundamental terms of opinion dynamics models.

Keywords: experimental validation, micro-dynamics rule, opinion dynamics, update rule

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Authors: Elizabeth O. Odewale, Sachithra T. Wanasinghe, Aaron S. Rury

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Cavity polaritons form when molecular excitons strongly couple to photons in carefully constructed optical cavities. These polaritons, which are hybrid light-matter states possessing a unique combination of photonic and excitonic properties, present the opportunity to manipulate the properties of various semiconductor materials. The systematic manipulation of materials through polariton formation could potentially improve the functionalities of many optoelectronic devices such as lasers, light-emitting diodes, photon-based quantum computers, and solar cells. However, the prospects of leveraging polariton formation for novel devices and device operation depend on more complete connections between the properties of molecular chromophores, and the hybrid light-matter states they form, which remains an outstanding scientific goal. Specifically, for most optoelectronic applications, it is paramount to understand how polariton formation affects the spectra of light absorbed by molecules coupled strongly to cavity photons. An essential feature of a polariton state is its dispersive energy, which occurs due to the enhanced spatial delocalization of the polaritons relative to bare molecules. To leverage the spatial delocalization of cavity polaritons, angle-resolved photoluminescence excitation spectroscopy was employed in characterizing light emission from the polaritonic states. Using lasers of appropriate energies, the polariton branches were resonantly excited to understand how molecular light absorption changes under different strong light-matter coupling conditions. Since an excited state has a finite lifetime, the photon absorbed by the polariton decays non-radiatively into lower-lying molecular states, from which radiative relaxation to the ground state occurs. The resulting fluorescence is collected across several angles of excitation incidence. By modeling the behavior of the light emission observed from the lower-lying molecular state and combining this result with the output of angle-resolved transmission measurements, inferences are drawn about how the behavior of molecules changes when they form polaritons. These results show how the intrinsic properties of molecules, such as the excitonic lifetime, affect the rate at which the polaritonic states relax. While it is true that the lifetime of the photon mediates the rate of relaxation in a cavity, the results from this study provide evidence that the lifetime of the molecular exciton also limits the rate of polariton relaxation.

Keywords: flourescece, molecules in cavityies, optical cavity, photoluminescence excitation, spectroscopy, strong coupling

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Authors: S. R. Dehghani, Y. S. Muzychka, G. F. Naterer

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The ice accretion of salt water on cold substrates creates brine-spongy ice. This type of ice is a mixture of pure ice and liquid brine. A real case of creation of this type of ice is superstructure icing which occurs on marine vessels and offshore structures in cold and harsh conditions. Transient heat transfer through this medium causes phase changes between brine pockets and pure ice. Salt rejection during the process of transient heat conduction increases the salinity of brine pockets to reach a local equilibrium state. In this process the only effect of passing heat through the medium is not changing the sensible heat of the ice and brine pockets; latent heat plays an important role and affects the mechanism of heat transfer. In this study, a new analytical model for evaluating heat transfer through brine-spongy ice is suggested. This model considers heat transfer and partial solidification and melting together. Properties of brine-spongy ice are obtained using properties of liquid brine and pure ice. A numerical solution using Method of Lines discretizes the medium to reach a set of ordinary differential equations. Boundary conditions are chosen using one of the applicable cases of this type of ice; one side is considered as a thermally isolated surface, and the other side is assumed to be suddenly affected by a constant temperature boundary. All cases are evaluated in temperatures between -20 C and the freezing point of brine-spongy ice. Solutions are conducted using different salinities from 5 to 60 ppt. Time steps and space intervals are chosen properly to maintain the most stable and fast solution. Variation of temperature, volume fraction of brine and brine salinity versus time are the most important outputs of this study. Results show that transient heat conduction through brine-spongy ice can create a various range of salinity of brine pockets from the initial salinity to that of 180 ppt. The rate of variation of temperature is found to be slower for high salinity cases. The maximum rate of heat transfer occurs at the start of the simulation. This rate decreases as time passes. Brine pockets are smaller at portions closer to the colder side than that of the warmer side. A the start of the solution, the numerical solution tends to increase instabilities. This is because of sharp variation of temperature at the start of the process. Changing the intervals improves the unstable situation. The analytical model using a numerical scheme is capable of predicting thermal behavior of brine spongy ice. This model and numerical solutions are important for modeling the process of freezing of salt water and ice accretion on cold structures.

Keywords: method of lines, brine-spongy ice, heat conduction, salt water

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Authors: Deisy Becerra, Edwar Perez, Nicolas Rios, Miguel Asuaje

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Progressing Cavity Pump (PCP) is a type of positive displacement pump that is being awarded greater importance as capable artificial lift equipment in the heavy oil field. The most commonly PCP used is driven single lobe pump that consists of a single external helical rotor turning eccentrically inside a double internal helical stator. This type of pump was analyzed by the experimental and Computational Fluid Dynamic (CFD) approach from the DCAB031 model located in a closed-loop arrangement. Experimental measurements were taken to determine the pressure rise and flow rate with a flow control valve installed at the outlet of the pump. The flowrate handled was measured by a FLOMEC-OM025 oval gear flowmeter. For each flowrate considered, the pump’s rotational speed and power input were controlled using an Invertek Optidrive E3 frequency driver. Once a steady-state operation was attained, pressure rise measurements were taken with a Sper Scientific wide range digital pressure meter. In this study, water and three Newtonian oils of different viscosities were tested at different rotational speeds. The CFD model implementation was developed on Star- CCM+ using an Overset Mesh that includes the relative motion between rotor and stator, which is one of the main contributions of the present work. The simulations are capable of providing detailed information about the pressure and velocity fields inside the device in laminar and unsteady regimens. The simulations have a good agreement with the experimental data due to Mean Squared Error (MSE) in under 21%, and the Grid Convergence Index (GCI) was calculated for the validation of the mesh, obtaining a value of 2.5%. In this case, three different rotational speeds were evaluated (200, 300, 400 rpm), and it is possible to show a directly proportional relationship between the rotational speed of the rotor and the flow rate calculated. The maximum production rates for the different speeds for water were 3.8 GPM, 4.3 GPM, and 6.1 GPM; also, for the oil tested were 1.8 GPM, 2.5 GPM, 3.8 GPM, respectively. Likewise, an inversely proportional relationship between the viscosity of the fluid and pump performance was observed, since the viscous oils showed the lowest pressure increase and the lowest volumetric flow pumped, with a degradation around of 30% of the pressure rise, between performance curves. Finally, the Productivity Index (PI) remained approximately constant for the different speeds evaluated; however, between fluids exist a diminution due to the viscosity.

Keywords: computational fluid dynamic, CFD, Newtonian fluids, overset mesh, PCP pressure rise

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Authors: Samuele Ghignoli, Valentina de Lorenzi, Gianmarco Ferri, Stefano Luin, Francesco Cardarelli

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Insulin and glucagon are the two essential hormones for maintaining proper blood glucose homeostasis, which is disrupted in Diabetes. A constantly growing research interest has been focused on the study of the subcellular structures involved in hormone secretion, namely insulin- and glucagon-containing granules, and on the mechanisms regulating their behaviour. Yet, while several successful attempts were reported describing the dynamic properties of insulin granules, little is known about their counterparts in α cells, the glucagon-containing granules. To fill this gap, we used αTC1 clone 9 cells as a model of α cells and ZIGIR as a fluorescent Zinc chelator for granule labelling. We started by using spatiotemporal fluorescence correlation spectroscopy in the form of imaging-derived mean square displacement (iMSD) analysis. This afforded quantitative information on the average dynamical and structural properties of glucagon granules having insulin granules as a benchmark. Interestingly, the iMSD sensitivity to average granule size allowed us to confirm that glucagon granules are smaller than insulin ones (~1.4 folds, further validated by STORM imaging). To investigate possible heterogeneities in granule dynamic properties, we moved from correlation spectroscopy to single particle tracking (SPT). We developed a MATLAB script to localize and track single granules with high spatial resolution. This enabled us to classify the glucagon granules, based on their dynamic properties, as ‘blocked’ (i.e., trajectories corresponding to immobile granules), ‘confined/diffusive’ (i.e., trajectories corresponding to slowly moving granules in a defined region of the cell), or ‘drifted’ (i.e., trajectories corresponding to fast-moving granules). In cell-culturing control conditions, results show this average distribution: 32.9 ± 9.3% blocked, 59.6 ± 9.3% conf/diff, and 7.4 ± 3.2% drifted. This benchmarking provided us with a foundation for investigating selected experimental conditions of interest, such as the glucagon-granule relationship with the cytoskeleton. For instance, if Nocodazole (10 μM) is used for microtubule depolymerization, the percentage of drifted motion collapses to 3.5 ± 1.7% while immobile granules increase to 56.0 ± 10.7% (remaining 40.4 ± 10.2% of conf/diff). This result confirms the clear link between glucagon-granule motion and cytoskeleton structures, a first step towards understanding the intracellular behaviour of this subcellular compartment. The information collected might now serve to support future investigations on glucagon granules in physiology and disease. Acknowledgment: This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 866127, project CAPTUR3D).

Keywords: glucagon granules, single particle tracking, correlation spectroscopy, ZIGIR

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Authors: Caroline Lavratti, Pedro Dal Lago, Gustavo Reinaldo, Gilson Dorneles, Andreia Bard, Laira Fuhr, Daniela Pochmann, Alessandra Peres, Luciane Wagner, Viviane Elsner

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Approximately 1% of the world's population is affected by schizophrenia (SZ), a chronic and debilitating neurodevelopmental disorder. Among possible factors, reduced levels of Brain-derived neurotrophic factor (BDNF) has been recognized in physiopathogenesis and course of SZ. In this context, peripheral BDNF levels have been used as a biomarker in several clinical studies, since this neurotrophin is able to cross the blood-brain barrier in a bi-directional manner and seems to present a strong correlation with the central nervous system fluid levels. The patients with SZ usually adopts a sedentary lifestyle, which has been partly associated with the increase in obesity incidence rates, metabolic syndrome, type 2 diabetes and coronary heart disease. On the other hand, exercise, a non-invasive and low cost intervention, has been considered an important additional therapeutic option for this population, promoting benefits to physical and mental health. To our knowledge, few studies have been pointed out that the positive effects of exercise in SZ patients are mediated, at least in part, to enhanced levels of BDNF after training. However, these studies are focused on evaluating the effect of single bouts of exercise of chronic interventions, data concerning the short- and long-term exercise outcomes on BDNF are scarce. Therefore, this study aimed to evaluate the effect of a concurrent exercise protocol (CEP) on plasma BDNF levels of SZ patients in different time-points. Material and Methods: This study was approved by the Research Ethics Committee of the Centro Universitário Metodista do IPA (no 1.243.680/2015). The participants (n=15) were subbmited to the CEP during 90 days, 3 times a week for 60 minutes each session. In order to evaluate the short and long-term effects of exercise, blood samples were collected pre, 30, 60 and 90 days after the intervention began. Plasma BDNF levels were determined with the ELISA method, from Sigma-Aldrich commercial kit (catalog number RAB0026) according to manufacturer's instructions. Results: A remarkable increase on plasma BDNF levels at 90 days after training compared to baseline (p=0.006) and 30 days (p=0.007) values were observed. Conclusion: Our data are in agreement with several studies that show significant enhancement on BDNF levels in response to different exercise protocols in SZ individuals. We might suggest that BDNF upregulation after training in SZ patients acts in a dose-dependent manner, being more pronounced in response to chronic exposure. Acknowledgments: This work was supported by Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)/Brazil.

Keywords: exercise, BDNF, schizophrenia, time-points

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Authors: Geum Yeon Sim, Jasal Patel, Anand Kumthekar, Stanley Wainapel

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A 65-year-old right-hand dominant African-American man, formerly employed as a security guard, was referred to Rehabilitation Medicine with bilateral hand stiffness and weakness. His past medical history was only significant for myelofibrosis, diagnosed 4 years earlier, for which he was receiving scheduled blood transfusions. Approximately 2 years ago, he began to notice stiffness and swelling in his non-dominant hand that progressed to pain and decreased strength, limiting his hand function. Similar but milder symptoms developed in his right hand several months later. There was no history of prior injury or exposure to cold. Physical examination showed enlargement of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints with finger flexion contractures, Swan-neck and Boutonniere deformities, and associated joint tenderness. Changes were more prominent in the left hand. X-rays showed mild osteoarthritis of several bilateral PIP joints. Anti-nuclear antibodies, rheumatoid factor, and cyclic citrullinated peptide antibodies were negative. MRI of the hand showed no erosions or synovitis. A rheumatology consultation was obtained, and the cause of his symptoms was attributed to myelofibrosis-related arthropathy with secondary osteoarthritis. The patient was tried on diclofenac cream and received a few courses of Occupational Therapy with limited functional improvement. Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by clonal proliferation of myeloid cells with variable morphologic maturity and hematopoietic efficiency. Rheumatic manifestations of malignancies include direct invasion, paraneoplastic presentations, secondary gout, or hypertrophic osteoarthropathy. PMF causes gradual bone marrow fibrosis with extramedullary metaplastic hematopoiesis in the liver, spleen, or lymph nodes. Musculoskeletal symptoms are not common and are not well described in the literature. The first reported case of myelofibrosis related arthritis was seronegative arthritis due to synovial invasion of myeloproliferative elements. Myelofibrosis has been associated with autoimmune diseases such as systemic lupus erythematosus, progressive systemic sclerosis, and rheumatoid arthritis. Gout has been reported in patients with myelofibrosis, and the underlying mechanism is thought to be related to the high turnover of nucleic acids that is greatly augmented in this disease. X-ray findings in these patients usually include erosive arthritis with synovitis. Treatment of underlying PMF is the treatment of choice, along with anti-inflammatory medications. Physicians should be cognizant of recognizing this rare entity in patients with PMF while maintaining clinical suspicion for more common causes of joint deformities, such as rheumatic diseases.

Keywords: myelofibrosis, arthritis, arthralgia, malignancy

Procedia PDF Downloads 101

Authors: Lee Boudreau, Ash Kumar Khaitu, Laura A. S. MacDonald

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In April 2015, a magnitude 7.8 earthquake struck Nepal, killing, injuring, and displacing thousands of people. The earthquake also damaged water and sanitation service networks, leading to a high risk of diarrheal disease and the associated negative health impacts. In response to the disaster, the Environment and Public Health Organization (ENPHO), a Kathmandu-based non-governmental organization, worked with the Centre for Affordable Water and Sanitation Technology (CAWST), a Canadian education, training and consulting organization, to develop two training programs to educate volunteers on water, sanitation, and hygiene (WASH) needs. The first training program was intended for acute response, with the second focusing on longer term recovery. A key focus was to equip the volunteers with the knowledge and skills to formulate useful WASH advice in the unanticipated circumstances they would encounter when working in affected areas. Within the first two weeks of the disaster, a two-day acute response training was developed, which focused on enabling volunteers to educate those affected by the disaster about local WASH issues, their link to health, and their increased importance immediately following emergency situations. Between March and October 2015, a total of 19 training events took place, with over 470 volunteers trained. The trained volunteers distributed hygiene kits and liquid chlorine for household water treatment. They also facilitated health messaging and WASH awareness activities in affected communities. A three-day recovery phase training was also developed and has been delivered to volunteers in Nepal since October 2015. This training focused on WASH issues during the recovery and reconstruction phases. The interventions and recommendations in the recovery phase training focus on long-term WASH solutions, and so form a link between emergency relief strategies and long-term development goals. ENPHO has trained 226 volunteers during the recovery phase, with training ongoing as of April 2016. In the aftermath of the earthquake, ENPHO found that its existing pool of volunteers were more than willing to help those in their communities who were more in need. By training these and new volunteers, ENPHO was able to reach many more communities in the immediate aftermath of the disaster; together they reached 11 of the 14 earthquake-affected districts. The collaboration between ENPHO and CAWST in developing the training materials was a highly collaborative and iterative process, which enabled the training materials to be developed within a short response time. By training volunteers on basic WASH topics during both the immediate response and the recovery phase, ENPHO and CAWST have been able to link immediate emergency relief to long-term developmental goals. While the recovery phase training continues in Nepal, CAWST is planning to decontextualize the training used in both phases so that it can be applied to other emergency situations in the future. The training materials will become part of the open content materials available on CAWST’s WASH Resources website.

Keywords: water and sanitation, emergency response, education and training, building resilience

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Authors: Massimiliano Panella, Sara Bortoluzzi, Sophia Russotto, Daniele Nicolini, Carmela Rinaldi

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Osteoporosis affects more than 200 million people worldwide. About 75% of osteoporosis cases are undiagnosed or diagnosed only when a bone fracture occurs. Since osteoporosis related fractures are significant determinants of the burden of disease and health and social costs of aging populations, we believe that this is the early identification and treatment of high-risk patients should be a priority in actual healthcare systems. Screening for osteoporosis by dual energy x-ray absorptiometry (DEXA) is not cost-effective for general population. An alternative is pulse-echo ultrasound (PEUS) because of the minor costs. To this end, we developed an early detection program for osteoporosis with PEUS, and we evaluated is possible impact and sustainability. We conducted a cross-sectional study including 1,050 people in Italy. Subjects with >1 major or >2 minor risk factors for osteoporosis were invited to PEUS bone mass density (BMD) measurement at the proximal tibia. Based on BMD values, subjects were classified as healthy subjects (BMD>0.783 g/cm²) and pathological including subjects with suspected osteopenia (0.783≤BMD>0.719 g/cm²) or osteoporosis (BMD ≤ 0.719 g/cm²). The responder rate was 60.4% (634/1050). According to the risk, PEUS scan was recommended to 436 people, of whom 300 (mean age 45.2, 81% women) accepted to participate. We identified 240 (80%) healthy and 60 (20%) pathological subjects (47 osteopenic and 13 osteoporotic). We observed a significant association between high risk people and reduced bone density (p=0.043) with increased risks for female gender, older ages, and menopause (p<0.01). The yearly cost of the screening program was 8,242 euros. With actual Italian fracture incidence rates in osteoporotic patients, we can reasonably expect in 20 years that at least 6 fractures will occur in our sample. If we consider that the mean costs per fracture in Italy is today 16,785 euros, we can estimate a theoretical cost of 100,710 euros. According to literature, we can assume that the early treatment of osteoporosis could avoid 24,170 euros of such costs. If we add the actual yearly cost of the treatments to the cost of our program and we compare this final amount of 11,682 euros to the avoidable costs of fractures (24,170 euros) we can measure a possible positive benefits/costs ratio of 2.07. As a major outcome, our study let us to early identify 60 people with a significant bone loss that were not aware of their condition. This diagnostic anticipation constitutes an important element of value for the project, both for the patients, for the preventable negative outcomes caused by the fractures, and for the society in general, because of the related avoidable costs. Therefore, based on our finding, we believe that the PEUS based screening performed could be a cost-effective approach to early identify osteoporosis. However, our study has some major limitations. In fact, in our study the economic analysis is based on theoretical scenarios, thus specific studies are needed for a better estimation of the possible benefits and costs of our program.

Keywords: osteoporosis, prevention, public health, screening

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Authors: Guanyu Jiang, Donghai Xu, Huanteng Liu

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After the Fukushima-Daiichi accident, the development of accident tolerant fuel cladding materials to improve reactor safety has become a hot topic in the field of nuclear industry. ZrO₂ has a satisfactory neutron economy and can guarantee the fission chain reaction process, which enables it to be a promising coating for zirconium alloy cladding. Maintaining a good corrosion resistance in primary coolant loop during normal operations of Pressurized Water Reactors is a prerequisite for ZrO₂ as a protective coating on zirconium alloy cladding. Research on the corrosion performance of ZrO₂ coating in nuclear water chemistry is relatively scarce, and existing reports failed to provide an in-depth explanation for the failure causes of ZrO₂ coating. Herein, a detailed corrosion process of ZrO₂ coating in lithiated water at 360 °C and 18.5 MPa was proposed based on experimental research and molecular dynamics simulation. Lithiated water with different LiOH solutions in the present work was deaerated and had a dissolved oxygen concentration of < 10 ppb. The concentration of Li (as LiOH) was determined to be 2.3 ppm, 70 ppm, and 500 ppm, respectively. Corrosion tests were conducted in a static autoclave. Modeling and corresponding calculations were operated on Materials Studio software. The calculation of adsorption energy and dynamics parameters were undertaken by the Energy task and Dynamics task of the Forcite module, respectively. The protective effect and failure mechanism of ZrO₂ coating on Zry-4 under varied LiOH concentrations was further revealed by comparison with the coating corrosion performance in pure water (namely 0 ppm Li). ZrO₂ coating provided a favorable corrosion protection with the occurrence of localized corrosion at low LiOH concentrations. Factors influencing corrosion resistance mainly include pitting corrosion extension, enhanced Li+ permeation, short-circuit diffusion of O²⁻ and ZrO₂ phase transformation. In highly-concentrated LiOH solutions, intergranular corrosion, internal oxidation, and perforation resulted in coating failure. Zr ions were released to coating surface to form flocculent ZrO₂ and ZrO₂ clusters due to the strong diffusion and dissolution tendency of α-Zr in the Zry-4 substrate. Considering that primary water of Pressurized Water Reactors usually includes 2.3 ppm Li, the stability of ZrO₂ make itself a candidate fuel cladding coating material. Under unfavorable conditions with high Li concentrations, more boric acid should be added to alleviate caustic corrosion of ZrO₂ coating once it is used. This work can provide some references to understand the service behavior of nuclear coatings under variable water chemistry conditions and promote the in-pile application of ZrO₂ coating.

Keywords: ZrO₂ coating, Zry-4, corrosion behavior, failure mechanism, LiOH concentration

Procedia PDF Downloads 86

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

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Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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Authors: Henda Gnakate Biba, Ndassa Mouafon Issa

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Dictionaries modeled on the Western model [tonic accent languages] are not suitable and do not account for tonal languages phonologically, which is why the [prosodic and phonological] ethnographic dictionary was designed. It is a glossary that expresses the tones and the rhythm of words. It recreates exactly the speaking or singing of a tonal language, and allows the non-speaker of this language to pronounce the words as if they were a native. It is a dictionary adapted to tonal languages. It was built from ethnomusicological theorems and phonological processes, according to Jean. J. Rousseau 1776 hypothesis /To say and to sing were once the same thing/. Each word in the French dictionary finds its corresponding language, ekaη. And each word ekaη is written on a musical staff. This ethnographic dictionary is also an inventive, original and innovative research thesis, but it is also an inventive, original and innovative research thesis. A contribution to the theoretical, musicological, ethno musicological and linguistic conceptualization of languages, giving rise to the practice of interlocution between the social and cognitive sciences, the activities of artistic creation and the question of modeling in the human sciences: mathematics, computer science, translation automation and artificial intelligence. When you apply this theory to any text of a folksong of a world-tone language, you do not only piece together the exact melody, rhythm, and harmonies of that song as if you knew it in advance but also the exact speaking of this language. The author believes that the issue of the disappearance of tonal languages and their preservation has been structurally resolved, as well as one of the greatest cultural equations related to the composition and creation of tonal, polytonal and random music. The experimentation confirming the theorization designed a semi-digital, semi-analog application which translates the tonal languages of Africa (about 2,100 languages) into blues, jazz, world music, polyphonic music, tonal and anatonal music and deterministic and random music). To test this application, I use a music reading and writing software that allows me to collect the data extracted from my mother tongue, which is already modeled in the musical staves saved in the ethnographic (semiotic) dictionary for automatic translation ( volume 2 of the book). Translation is done (from writing to writing, from writing to speech and from writing to music). Mode of operation: you type a text on your computer, a structured song (chorus-verse), and you command the machine a melody of blues, jazz and, world music or, variety etc. The software runs, giving you the option to choose harmonies, and then you select your melody.

Keywords: music, language, entenglement, science, research

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Authors: Robert Pellerin, Michel Gamache, Remi Trudeau, Nathalie Perrier

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The context of large engineering projects is particularly favorable to the appearance of engineering changes and contractual modifications. These elements are potential causes for claims. In this paper, we investigate one of the critical components of the claim management process: the calculation of the impacts of changes in terms of losses of productivity due to the need to accelerate some project activities. When project changes are initiated, delays can arise. Indeed, project activities are often executed in fast-tracking in an attempt to respect the completion date. But the acceleration of project execution and the resulting rework can entail important costs as well as induce productivity losses. In the past, numerous methods have been proposed to quantify the duration of delays, the gains achieved by project acceleration, and the loss of productivity. The calculation related to those changes can be divided into two categories: direct cost and indirect cost. The direct cost is easily quantifiable as opposed to indirect costs which are rarely taken into account during the calculation of the cost of an engineering change or contract modification despite several research projects have been made on this subject. However, proposed models have not been accepted by companies yet, nor they have been accepted in court. Those models require extensive data and are often seen as too specific to be used for all projects. These techniques are also ignoring the resource constraints and the interdependencies between the causes of delays and the delays themselves. To resolve this issue, this research proposes a simulation model that mimics how major engineering changes or contract modifications are handled in large construction projects. The model replicates the use of overtime in a reactive scheduling mode in order to simulate the loss of productivity present when a project change occurs. Multiple tests were conducted to compare the results of the proposed simulation model with statistical analysis conducted by other researchers. Different scenarios were also conducted in order to determine the impact the number of activities, the time of occurrence of the change, the availability of resources, and the type of project changes on productivity loss. Our results demonstrate that the number of activities in the project is a critical variable influencing the productivity of a project. When changes occur, the presence of a large number of activities leads to a much lower productivity loss than a small number of activities. The speed of reducing productivity for 30-job projects is about 25 percent faster than the reduction speed for 120-job projects. The moment of occurrence of a change also shows a significant impact on productivity. Indeed, the sooner the change occurs, the lower the productivity of the labor force. The availability of resources also impacts the productivity of a project when a change is implemented. There is a higher loss of productivity when the amount of resources is restricted.

Keywords: engineering changes, indirect costs overtime, productivity, scheduling, simulation

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Authors: Antonina A. Shumakova, Sergey A. Khotimchenko

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The relevance of research is associated, on the one hand, with an ever-increasing volume of production and the expansion of the scope of application of engineered nanomaterials (ENMs), and on the other hand, with the lack of sufficient scientific information on the nature of the interactions of nanoparticles (NPs) with components of biogenic and abiogenic origin. In particular, studying the effect of ENMs (TiO2 NPs, SiO2 NPs, Al2O3 NPs, fullerenol) on the toxicometric characteristics of common contaminants such as lead and cadmium is an important hygienic task, given the high probability of their joint presence in food products. Data were obtained characterizing a multidirectional change in the toxicity of model toxicants when they are co-administered with various types of ENMs. One explanation for this fact is the difference in the adsorption capacity of ENMs, which was further studied in in vitro studies. For this, a method was proposed based on in vitro modeling of conditions simulating the environment of the small intestine. It should be noted that the obtained data are in good agreement with the results of in vivo experiments: - with the combined administration of lead and TiO2 NPs, there were no significant changes in the accumulation of lead in rat liver; in other organs (kidneys, spleen, testes and brain), the lead content was lower than in animals of the control group; - studying the combined effect of lead and Al2O3 NPs, a multiple and significant increase in the accumulation of lead in rat liver was observed with an increase in the dose of Al2O3 NPs. For other organs, the introduction of various doses of Al2O3 NPs did not significantly affect the bioaccumulation of lead; - with the combined administration of lead and SiO2 NPs in different doses, there was no increase in lead accumulation in all studied organs. Based on the data obtained, it can be assumed that at least three scenarios of the combined effects of ENMs and chemical contaminants on the body: - ENMs quite firmly bind contaminants in the gastrointestinal tract and such a complex becomes inaccessible (or inaccessible) for absorption; in this case, it can be expected that the toxicity of both ENMs and contaminants will decrease; - the complex formed in the gastrointestinal tract has partial solubility and can penetrate biological membranes and / or physiological barriers of the body; in this case, ENMs can play the role of a kind of conductor for contaminants and, thus, their penetration into the internal environment of the body increases, thereby increasing the toxicity of contaminants; - ENMs and contaminants do not interact with each other in any way, therefore the toxicity of each of them is determined only by its quantity and does not depend on the quantity of another component. Authors hypothesized that the degree of adsorption of various elements on the surface of ENMs may be a unique characteristic of their action, allowing a more accurate understanding of the processes occurring in a living organism.

Keywords: absorption, cadmium, engineered nanomaterials, lead

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Authors: Yazmin Pineda Zapata

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Leading a complete school and culture transformation can be a daunting task for any administrator. This is especially true when change agents are advocating for inclusive reform in their schools. As leaders embark on this journey, they must ascertain that an inclusive environment is not a place, a classroom, or a resource setting; it is a place of acceptance nurtured by supportive and meaningful learning opportunities where all students can thrive. A qualitative approach, phenomenology, was used to investigate principals’ actions and behaviors that supported inclusive schooling for students with disabilities. Specifically, this study sought to answer the following research question: How do leaders develop and maintain inclusive education? Fourteen K-12 principals purposefully selected from various sources (e.g., School Wide Integrated Framework for Transformation (SWIFT), The Maryland Coalition for Inclusive Education (MCIE), The Arc of Texas Inclusion Works organization, The Association for Persons with Severe Handicaps (TASH), the CAL State Summer Institute in San Marcos, and the PEAK Parent Center and/or other recognitions were interviewed individually using a semi-structured protocol. Upon completion of data collection, all interviews were transcribed and marked using A priori coding to analyze the responses and establish a correlation among Villa and Thousand’s five organizational supports to achieve inclusive educational reform: Vision, Skills, Incentives, Resources, and Action Plan. The findings of this study reveal the insights of principals who met specific criteria and whose schools had been highlighted as exemplary inclusive schools. Results show that by implementing the five organizational supports, principals were able to develop and sustain successful inclusive environments where both teachers and students were motivated, made capable, and supported through the redefinition and restructuring of systems within the school. Various key details of the five variables for change depict essential components within these systems, which include quality professional development, coaching and modeling of co-teaching strategies, collaborative co-planning, teacher leadership, and continuous stakeholder (e.g., teachers, students, support staff, and parents) involvement. The administrators in this study proved the valuable benefits of inclusive education for students with disabilities and their typically developing peers. Together, along with their teaching and school community, school leaders became capable stakeholders that promoted the vision of inclusion, planned a structured approach, and took action to make it a reality.

Keywords: Inclusive education, leaders, principals, shared-decision making, shared leadership, special education, sustainable change

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Authors: Yesim Tumsek, Erkan Celebi

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In order to simulate the infinite soil medium for soil-foundation interaction problem, the essential geotechnical parameter on which the foundation stiffness depends, is the value of soil shear modulus. This parameter directly affects the site and structural response of the considered model under earthquake ground motions. Strain-dependent shear modulus under cycling loads makes difficult to estimate the accurate value in computation of foundation stiffness for the successful dynamic soil-structure interaction analysis. The aim of this study is to discuss in detail how to use the appropriate value of soil shear modulus in the computational analyses and to evaluate the effect of the variation in shear modulus with strain on the impedance functions used in the sub-structure method for idealizing the soil-foundation interaction problem. Herein, the impedance functions compose of springs and dashpots to represent the frequency-dependent stiffness and damping characteristics at the soil-foundation interface. Earthquake-induced vibration energy is dissipated into soil by both radiation and hysteretic damping. Therefore, flexible-base system damping, as well as the variability in shear strengths, should be considered in the calculation of impedance functions for achievement a more realistic dynamic soil-foundation interaction model. In this study, it has been written a Matlab code for addressing these purposes. The case-study example chosen for the analysis is considered as a 4-story reinforced concrete building structure located in Istanbul consisting of shear walls and moment resisting frames with a total height of 12m from the basement level. The foundation system composes of two different sized strip footings on clayey soil with different plasticity (Herein, PI=13 and 16). In the first stage of this study, the shear modulus reduction factor was not considered in the MATLAB algorithm. The static stiffness, dynamic stiffness modifiers and embedment correction factors of two rigid rectangular foundations measuring 2m wide by 17m long below the moment frames and 7m wide by 17m long below the shear walls are obtained for translation and rocking vibrational modes. Afterwards, the dynamic impedance functions of those have been calculated for reduced shear modulus through the developed Matlab code. The embedment effect of the foundation is also considered in these analyses. It can easy to see from the analysis results that the strain induced in soil will depend on the extent of the earthquake demand. It is clearly observed that when the strain range increases, the dynamic stiffness of the foundation medium decreases dramatically. The overall response of the structure can be affected considerably because of the degradation in soil stiffness even for a moderate earthquake. Therefore, it is very important to arrive at the corrected dynamic shear modulus for earthquake analysis including soil-structure interaction.

Keywords: clay soil, impedance functions, soil-foundation interaction, sub-structure approach, reduced shear modulus

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Authors: Vlad Andrei Raducanu, Mariana Lucia Angelescu, Ion Cinca, Vasile Danut Cojocaru, Doina Raducanu

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By using smart digital tools, such as generative design (GD) and digital fabrication (DF), problems of high actuality concerning resources optimization (materials, energy, time) can be solved and applications or products of free-form type can be created. In the new digital technology materials are active, designed in response to a set of performance requirements, which impose a total rethinking of old material practices. The article presents the design procedure key steps of a free-form architectural object - a column type one with connections to get an adaptive 3D surface, by using the parametric design methodology and by exploiting the properties of conventional metallic materials. In parametric design the form of the created object or space is shaped by varying the parameters values and relationships between the forms are described by mathematical equations. Digital parametric design is based on specific procedures, as shape grammars, Lindenmayer - systems, cellular automata, genetic algorithms or swarm intelligence, each of these procedures having limitations which make them applicable only in certain cases. In the paper the design process stages and the shape grammar type algorithm are presented. The generative design process relies on two basic principles: the modeling principle and the generative principle. The generative method is based on a form finding process, by creating many 3D spatial forms, using an algorithm conceived in order to apply its generating logic onto different input geometry. Once the algorithm is realized, it can be applied repeatedly to generate the geometry for a number of different input surfaces. The generated configurations are then analyzed through a technical or aesthetic selection criterion and finally the optimal solution is selected. Endless range of generative capacity of codes and algorithms used in digital design offers various conceptual possibilities and optimal solutions for both technical and environmental increasing demands of building industry and architecture. Constructions or spaces generated by parametric design can be specifically tuned, in order to meet certain technical or aesthetical requirements. The proposed approach has direct applicability in sustainable architecture, offering important potential economic advantages, a flexible design (which can be changed until the end of the design process) and unique geometric models of high performance.

Keywords: parametric design, algorithmic procedures, free-form architectural object, sustainable architecture

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Authors: Karolina Ordon, Sandrine Coste, Malgorzata Makowska-Janusik, Abdelhadi Kassiba

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Photocatalytic processes play key role in the production of a new source of energy (as hydrogen), design of self-cleaning surfaces or for the environment preservation. The most challenging task deals with the purification of water distinguished by high efficiency. In the mentioned process, organic pollutants in solutions are decomposed to the simple, non-toxic compounds as H2O and CO2. The most known photocatalytic materials are ZnO, CdS and TiO2 semiconductors with a particular involvement of TiO2 as an efficient photocatalysts even with a high band gap equal to 3.2 eV which exploit only UV radiation from solar emitted spectrum. However, promising material with visible light induced photoactivity was searched through the monoclinic polytype of BiVO4 which has energy gap about 2.4 eV. As required in heterogeneous photocatalysis, the high contact surface is required. Also, BiVO4 as photocatalyst can be optimized by increasing its surface area by achieving the mesoporous structure synthesize. The main goal of the present work consists in the synthesis and characterization of BiVO4 mesoporous thin film. The synthesis method based on sol-gel was carried out using a standard surfactants such as P123 and F127. The thin film was deposited by spin and dip coating method. Then, the structural analysis of the obtained material was performed thanks to X-ray diffraction (XRD) and Raman spectroscopy. The surface of resulting structure was investigated using a scanning electron microscopy (SEM). The computer simulations based on modeling the optical and electronic properties of bulk BiVO4 by using DFT (density functional theory) methodology were carried out. The semiempirical parameterized method PM6 was used to compute the physical properties of BiVO4 nanostructures. The Raman and IR absorption spectra were also measured for synthesized mesoporous material, and the results were compared with the theoretical predictions. The simulations of nanostructured BiVO4 have pointed out the occurrence of quantum confinement for nanosized clusters leading to widening of the band gap. This result overcame the relevance of nanosized objects to harvest wide part of the solar spectrum. Also, a balance was searched experimentally through the mesoporous nature of the films devoted to enhancing the contact surface as required for heterogeneous catalysis without to lower the nanocrystallite size under some critical sizes inducing an increased band gap. The present contribution will discuss the relevant features of the mesoporous films with respect to their photocatalytic responses.

Keywords: bismuth vanadate, photocatalysis, thin film, quantum-chemical calculations

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Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Zinc is a vital element required for growth and development. This fact makes zinc important, particularly for children. It maintains normal cellular structure and functions. This essential element appears to have protective effects against coronary artery disease and cardiomyopathy. Higher serum zinc levels are associated with lower risk of cardiovascular diseases (CVDs). There is a significant association between low serum zinc levels and heart failure. Zinc may be a potential biomarker of cardiovascular health. High sensitive cardiac troponin T (hs-cTnT) and cardiac myosin binding protein C (cMyBP-C) are new generation markers used for prediagnosis, diagnosis, and prognosis of CVDs. The aim of this study is to determine zinc as well as new generation cardiac markers profiles in children with normal body mass index (N-BMI), obese (OB), morbid obese (MO) children, and children with metabolic syndrome (MetS) findings. The association among them will also be investigated. Four study groups were constituted. The study protocol was approved by the institutional Ethics Committee of Tekirdag Namik Kemal University. Parents of the participants filled informed consent forms to participate in the study. Group 1 is composed of 44 children with N-BMI. Group 2 and Group 3 comprised 43 OB and 45 MO children, respectively. Forty-five MO children with MetS findings were included in Group 4. World Health Organization age- and sex-adjusted BMI percentile tables were used to constitute groups. These values were 15-85, 95-99, and above 99 for N-BMI, OB, and MO, respectively. Criteria for MetS findings were determined. Routine biochemical analyses, including zinc, were performed. High sensitive-cTnT and cMyBP-C concentrations were measured by kits based on enzyme-linked immunosorbent assay principle. Appropriate statistical tests within the scope of SPSS were used for the evaluation of the study data. p<0.05 was accepted as statistically significant. Four groups were matched for age and gender. Decreased zinc concentrations were measured in Groups 2, 3, and 4 compared to Group 1. Groups did not differ from one another in terms of hs-cTnT. There were statistically significant differences between cMyBP-C levels of MetS group and N-BMI as well as OB groups. There was an increasing trend going from N-BMI group to MetS group. There were statistically significant negative correlations between zinc and hs-cTnT as well as cMyBP-C concentrations in MetS group. In conclusion, inverse correlations detected between zinc and new generation cardiac markers (hs-TnT and cMyBP-C) have pointed out that decreased levels of this physiologically essential trace element accompany increased levels of hs-cTnT as well as cMyBP-C in children with MetS. This finding emphasizes that both zinc and these new generation cardiac markers may be evaluated as biomarkers of cardiovascular health during severe childhood obesity precipitated with MetS findings and also suggested as the messengers of the future risk in the adulthood periods of children with MetS.

Keywords: cardiac myosin binding protein-C, cardiovascular diseases, children, high sensitive cardiac troponin T, obesity

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Authors: Gianluca Castelnuovo, Giada Pietrabissa, Gian Mauro Manzoni, Margherita Novelli, Emanuele Maria Giusti, Roberto Cattivelli, Enrico Molinari

Abstract:

Diabesity could be defined as a new global epidemic of obesity and being overweight with many complications and chronic conditions. Such conditions include not only type 2 diabetes, but also cardiovascular diseases, hypertension, dyslipidemia, hypercholesterolemia, cancer, and various psychosocial and psychopathological disorders. The financial direct and indirect burden (considering also the clinical resources involved and the loss of productivity) is a real challenge in many Western health-care systems. Recently the Lancet journal defined diabetes as a 21st-century challenge. In order to promote patient compliance in diabesity treatment reducing costs, evidence-based interventions to improve weight-loss, maintain a healthy weight, and reduce related comorbidities combine different treatment approaches: dietetic, nutritional, physical, behavioral, psychological, and, in some situations, pharmacological and surgical. Moreover, new technologies can provide useful solutions in this multidisciplinary approach, above all in maintaining long-term compliance and adherence in order to ensure clinical efficacy. Psychological therapies with diet and exercise plans could better help patients in achieving weight loss outcomes, both inside hospitals and clinical centers and during out-patient follow-up sessions. In the management of chronic diseases clinical psychology play a key role due to the need of working on psychological conditions of patients, their families and their caregivers. mHealth approach could overcome limitations linked with the traditional, restricted and highly expensive in-patient treatment of many chronic pathologies: one of the best up-to-date application is the management of obesity with type 2 diabetes, where mHealth solutions can provide remote opportunities for enhancing weight reduction and reducing complications from clinical, organizational and economic perspectives. A stepped care mHealth-based approach is an interesting perspective in chronic care management of obesity with type 2 diabetes. One promising future direction could be treating obesity, considered as a chronic multifactorial disease, using a stepped-care approach: -mhealth or traditional based lifestyle psychoeducational and nutritional approach. -health professionals-driven multidisciplinary protocols tailored for each patient. -inpatient approach with the inclusion of drug therapies and other multidisciplinary treatments. -bariatric surgery with psychological and medical follow-up In the chronic care management of globesity mhealth solutions cannot substitute traditional approaches, but they can supplement some steps in clinical psychology and medicine both for obesity prevention and for weight loss management.

Keywords: clinical health psychology, mhealth, obesity, type 2 diabetes, stepped care, chronic care management

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Authors: Lei Zhou, Dan Li, Ruiqi Ren, Chao Li, Yali Wang, Daxin Ni, Zijian Feng, Timothy M. Uyeki, Qun Li

Abstract:

Since the first human infections with avian influenza A(H7N9) virus were identified in early 2013, 1533 cases of laboratory-confirmed A(H7N9) virus infections were reported and confirmed as of September 13, 2017. The fifth epidemic was defined as starting from September 1, 2016, and the number of A(H7N9) cases has surged since the end of December in 2016. On February 18, 2017, the A(H7N9) cases who were infected with highly pathogenic avian influenza (HPAI) virus was reported from Southern China. The HPAI A(H7N9) cases were identified and then an investigation and analyses were conducted to assess whether disease severity in humans has changed with HPAI A(H7N9) compared with low pathogenic avian influenza (LPAI) A(H7N9) virus infection. Methods: All confirmed cases with A(H7N9) virus infections reported throughout mainland China from September 1, 2016, to September 13, 2017, were included. Cases' information was extracted from field investigation reports and the notifiable infectious surveillance system to describe the demographic, clinical, and epidemiologic characteristics. Descriptive statistics were used to compare HPAI A(H7N9) cases with all LPAI A(H7N9) cases reported during the fifth epidemic. Results: A total of 27 cases of HPAI A(H7N9) virus were identified infection from five provinces, including Guangxi (44%), Guangdong (33%), Hunan (15%), Hebei (4%) and Shangxi (4%). The median age of cases of HPAI A(H7N9) virus infection was 60 years (range, 15 to 80) and most of them were male (59%) and lived in rural areas (78%). All 27 cases had live poultry related exposures within 10 days before their illness onset. In comparison with LPAI A(H7N9) case-patients, HPAI A(H7N9) case-patients were significantly more likely to live in rural areas (78% vs. 51%; p = 0.006), have exposure to the sick or dead poultry (56% vs. 19%; p = 0.000), and be hospitalized earlier (median 3 vs. 4 days; p = 0.007). No significant differences were observed in median age, sex, prevalence of underlying chronic medical conditions, median time from illness onset to first medical service seeking, starting antiviral treatment, and diagnosis. Although the median time from illness onset to death (9 vs. 13 days) was shorter and the overall case-fatality proportion (48% vs. 38%) was higher for HPAI A(H7N9) case-patients than for LPAI A(H7N9) case-patients, these differences were not statistically significant. Conclusions: Our findings indicate that HPAI A(H7N9) virus infection was associated with exposure to sick and dead poultry in rural areas when visited live poultry market or in the backyard. In the fifth epidemic in mainland China, HPAI A (H7N9) case-patients were hospitalized earlier than LPAI A(H7N9) case-patients. Although the difference was not statistically significant, the mortality of HPAI A (H7N9) case-patients was obviously higher than that of LPAI A(H7N9) case-patients, indicating a potential severity change of HPAI A(H7N9) virus infection.

Keywords: Avian influenza A (H7N9) virus, highly pathogenic avian influenza (HPAI), case-patients, poultry

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