Search results for: head and neck

Authors: Safa Gharbi, Hayfa Zgaya, Nesrine Zoghlami, Slim Hammadi, Cyril De Barbarin, Laurent Vinatier, Christiane Coupier

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Increasing productivity and quality of service, improving the working comfort and ensuring the efficiency of all processes are important challenges for every warehouse. The order picking is recognized to be the most important and costly activity of all the process in warehouses. This paper presents a new approach using Augmented Reality (AR) in the field of logistics. It aims to create a Head-Up Display (HUD) interface with a Warehouse Management System (WMS), using AR glasses. Integrating AR technology allows the optimization of order picking by reducing time of picking process, increasing the efficiency and delivering quickly. The picker will be able to access immediately to all the information needed for his tasks. All the information is displayed when needed in the field of vision (FOV) of the operator, without any action requested from him. These research works are part of the industrial project RASL (Réalité Augmentée au Service de la Logistique) which gathers two major partners: the LAGIS (Laboratory of Automatics, Computer Engineering and Signal Processing in Lille-France) and Genrix Group, European leader in warehouses logistics, who provided his software for implementation, and his logistics expertise.

Keywords: Augmented Reality (AR), logistics and optimization, Warehouse Management System (WMS), Head-Up Display (HUD)

Procedia PDF Downloads 456

Authors: J. E. Cobbinah

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One of the most challenging issues confronting schools is good leadership succession planning. Experts argue that, although the idea of leadership succession planning is one of the strategies or practices that can help sustain improvement and promote continuity of good leadership, seem to have been neglected in many schools over the years. Appointment of head teachers in senior high schools is based on long service or one’s ability to demonstrate his/her competence in a leadership selection interview. There is no clear and well-structured leadership succession plan, before leadership position is filled, while school leadership succession planning seem to be an issue that nobody talks about. In faith-based schools the issue is even worse, because religious groups impose whoever they consider strong in the faith on schools as leaders, irrespective of the individual competence, ability to take up challenges associated with individuals’ preparedness to take up leadership position. Therefore, the present study examined the nature (including type) of leadership succession plans in faith-based senior high schools and its associated challenges. Convergent mixed method design was employed to effectively achieve the objectives of the study. The data collection strategies involved the use of interviews, questionnaires, and reviews of secondary data. The data was gathered from students, school leaders (head teachers, deputy heads, and head of departments), selected parents teachers associated members, school management committee members and members from school governors. The results show that governors of faith-based schools are making efforts to enhance education quality, by making school leadership accountable, the absence and the neglect of clear, and well-structured leadership succession plan has some negative outcomes. Unsustainable students’ academic performance, lack of support from existing staffs and senior leaders and lack of support in the implementation of school improvement plan. It would be concluded that, faith-based schools should focus on leadership competence and abilities in the selection process of potential school leaders to achieve a good succession plan rather than appointing leaders who are affiliates of one’s faith.

Keywords: school leadership, succession planning, faith-based schools, school governors

Procedia PDF Downloads 407

Authors: Chih-Yang Liao

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Baseball is usually played outdoors in the warmest months of the year. Therefore, baseball players are susceptible to the influence of the hot environment. It has been shown that hitting performance is increased in games played in warm weather, compared to in cold weather, in Major League Baseball. Intermittent cooling during sporting events can prevent the risk of hyperthermia and increase endurance performance. However, the effects of cooling during baseball games played in a hot environment are unclear. This study adopted a cross-over design. Ten Division I collegiate male baseball players in Taiwan volunteered to participate in this study. Each player played two simulated baseball games, with one day in between. Five of the players received intermittent cooling during the first simulated game, while the other five players received intermittent cooling during the second simulated game. The participants were covered in neck and forehand regions for 6 min with towels that were soaked in icy salt water 3 to 4 times during the games. The participants received the cooling treatment in the dugout when they were not on the field for defense or hitting. During the 2 simulated games, the temperature was 31.1-34.1°C and humidity was 58.2-61.8%, with no difference between the two games. Ratings of perceived exertion, thermal sensation, tympanic and forehead skin temperature immediately after each defensive half-inning and after cooling treatments were recorded. Ratings of perceived exertion were measured using the Borg 10-point scale. The thermal sensation was measured with a 6-point scale. The tympanic and skin temperature was measured with infrared thermometers. The data were analyzed with a two-way analysis of variance with repeated measurement. The results showed that intermitted cooling significantly reduced ratings of perceived exertion and thermal sensation. Forehead skin temperature was also significantly decreased after cooling treatments. However, the tympanic temperature was not significantly different between the two trials. In conclusion, intermittent cooling in the neck and forehead regions was effective in alleviating the perceived exertion and heat sensation. However, this cooling intervention did not affect the core temperature. Whether intermittent cooling has any impact on hitting or pitching performance in baseball players warrants further investigation.

Keywords: baseball, cooling, ratings of perceived exertion, thermal sensation

Procedia PDF Downloads 125

Authors: Adhara Puspa Noorita, Azkiyatin Nailil M., Rita Aryanti, Sushanti Nuraini, Pujiati Abbas, Suparmi

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T-Dabuto is a tea made from leaves and fruits of parijoto (Madinella speciosa L.), which flavonoid, saponin and tanin contained in that tea are reported have diarrhea-caused antibacterial activity. However, the in vivo antidiarrhea effect have not clear yet. This study was conducted to determine the effect of T-DABUTO to faecal characteristics in male Balb/C-mice induced oleum ricini. Experimental research with post-test only control group design was conducted using 35 young male mice strain Balb-C which was divided into 5 groups. All groups were induced by 0.7 ml/ head of oleum ricini and 3 hours later followed by aquadest for first group, while the 2nd, 3rd, 4th and 5th group were treated by T-DABUTO solution with 75 mg/kgBW, 150 mg/kgBW, 300 mg/kgBW, and 600 mg/kgBW respectively as 0.7 ml/ head/ 0.5 hous for 8 hours. Feces collected were used to identify the frequency, absorbtion diameter and fecal weight. T-DABUTO on dose 75 mg/kg BW has the highest antidiarrhea activity which the mean of frequency defecation, water feacal absorbsion and feacal weight were 1.71±0.95 times, 0.38±0.49 mm, 0.43±0.28 mg, respectively. The T-DABUTO treatment did not influence the body weight of diarrheal mice. The T-DABUTO is potential as one of natural diarrhea tratment, especially in children.

Keywords: diarrhea, flavonid, tannin, saponin

Procedia PDF Downloads 501

Authors: Ashwini Shripatwar, Mayur Biyani, Nikhil Rao, Rajendra Bodake, Sachin Sane

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This paper documents the correlation of valve cover sealing, cracking, and warpage Finite Element Modelling with observations on engine test development. The valve cover is a component mounted on engine head with a gasket which provides sealing against oil which flows around camshaft, valves, rockers, and other overhead components. Material nonlinearity and contact nonlinearity characteristics are taken into consideration because the valve cover is made of a composite material having temperature dependent elastic-plastic properties and because the gasket load-deformation curve is also nonlinear. The leakage is observed between the valve cover and the engine head due to the insufficient contact pressure. The crack is observed on the valve cover due to force application at a region with insufficient stiffness and with elevated temperature. The valve cover shrinkage is observed during the disassembly process on hot exhaust side bolt holes after the engine has been running. In this paper, an analytical approach is developed to correlate a Finite Element Model with the observed failures and to address the design issues associated with the failure modes in question by making design changes in the model.

Keywords: cracking issue, gasket sealing analysis, nonlinearity of contact and material, valve cover

Procedia PDF Downloads 113

Authors: Omar Nouri, Wafa Mnejja, Nejla Fourati, Fatma Dhouib, Wicem Siala, Ilhem Charfeddine, Afef Khanfir, Jamel Daoud

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Background and objective: Induction chemotherapy (IC) followed by concomitant chemo radiotherapy with intensity modulated radiation (IMRT) technique is actually the recommended treatment modality for locally advanced nasopharyngeal carcinomas (NPC). The aim of this study was to evaluate the prognostic factors predicting loco regional relapse with this new treatment protocol. Patients and methods: A retrospective study of 52 patients with NPC treated between June 2016 and July 2019. All patients received IC according to the protocol of the Head and Neck Radiotherapy Oncology Group (Gortec) NPC 2006 (3 TPF courses) followed by concomitant chemo radiotherapy with weekly cisplatin (40 mg / m2). Patients received IMRT with integrated simultaneous boost (SIB) of 33 daily fractions at a dose of 69.96 Gy for high-risk volume, 60 Gy for intermediate risk volume and 54 Gy for low-risk volume. Median age was 49 years (19-69) with a sex ratio of 3.3. Forty five tumors (86.5%) were classified as stages III - IV according to the 2017 UICC TNM classification. Loco regional relapse (LRR) was defined as a local and/or regional progression that occurs at least 6 months after the end of treatment. Survival analysis was performed according to Kaplan-Meier method and Log-rank test was used to compare anatomy clinical and therapeutic factors that may influence loco regional free survival (LRFS). Results: After a median follow up of 42 months, 6 patients (11.5%) experienced LRR. A metastatic relapse was also noted for 3 of these patients (50%). Target volumes coverage was optimal for all patient with LRR. Four relapses (66.6%) were in high-risk target volume and two (33.3%) were borderline. Three years LRFS was 85,9%. Four factors predicted loco regional relapses: histologic type other than undifferentiated (UCNT) (p=0.027), a macroscopic pre chemotherapy tumor volume exceeding 100 cm³ (p=0.005), a reduction in IC doses exceeding 20% (p=0.016) and a total cumulative cisplatin dose less than 380 mg/m² (p=0.0.34). TNM classification and response to IC did not impact loco regional relapses. Conclusion: For nasopharyngeal carcinoma, tumors with initial high volume and/or histologic type other than UCNT, have a higher risk of loco regional relapse. Therefore, they require a more aggressive therapeutic approaches and a suitable monitoring protocol.

Keywords: loco regional relapse, modulation intensity radiotherapy, nasopharyngeal carcinoma, prognostic factors

Procedia PDF Downloads 103

Authors: C. G. Sawant, C. S. Patil

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The investigation was conducted during January 2016 on Farmer’s field at Nandur Madhyameshwar, Tq. Niphad, Dist. Nashik (Maharashtra: India) on bio-efficacy of newer insecticides against Plutella xylostella L. infesting cabbage. The cabbage crop (var. Saint) was raised according to package of practices except for plant protection measures. Six newer insecticides along with two conventional insecticides and one synthetic pyrethroid were applied twice at 30 and 55 days after transplanting. Insecticidal solutions were diluted in water (375-500 L ha-1) and applied using knapsack sprayer (16L) with hollow cone nozzle. Treatments included indoxacarb @ 40 g a.i.ha-1, spinosad @ 17.5 g a.i.ha-1, flubendiamide @18.24 g a.i. ha-1, diafenthiuron @ 300 g a. i. ha-1, emamectin benzoate @ 10 g a. i. ha-1, chlorantraniliprole @ 10 g a. i. ha-1, quinalphos @ 250 g a. i. ha-1, triazophos @ 500 g a. i. ha-1, bifenthrin @ 50 g a.i. ha-1 and untreated control. The larvae were counted on head and outside the head. Observations were recorded one day before spray (Precount) and 1,3,7,14 days after spray. Results revealed that all the insecticidal treatments were significantly superior over untreated control by recording lower larval count. Among the insecticidal treatments, significantly lowest number of larvae of diamondback moth was recorded in chlorantraniliprole @ 10 g a.i.ha-1 (1.00 larvae plant-1) followed by spinosad @ 17.5 g a.i. ha-1 (1.45 larvae plant-1 and flubendiamide 18.24 g a.i. ha-1(1.53 larvae plant-1). The efficacy of insecticides reflected on yield of marketable cabbage heads by recording 242.27 qt ha-1 (1:33.38) in the treatment of chlorantraniliprole @ 10 g a.i.ha-1. It was followed by spinosad @ 17.5 g a.i. ha-1 with 236.91 qt ha-1 (1:24.92) and flubendiamide 18.24 g a.i. ha-1 with 228.49 qt ha-1 (1:30.43).

Keywords: bio-efficacy, cabbage, chlorantraniliprole, Plutella xylostella L.

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Authors: Eitedal Daoud, Reda M.Daoud, Khaled Abdel-Wahhab, Maha M.Saber, Lobna Saber

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Background: Cis-platin is a widely used chemotherapeutic drug to treat many malignant disorders including head and neck malignancies. Oto-nephrotxicity is an important and dose - limiting side effect of cis - platin therapy. Nowadays, more attention had been paid to oto-toxicity caused with cis-platin. Aim of the Work: This study was designed to investigate the potential protective effect of Whey protein (WP) against cis-platin induced ototoxicity compared to the effect of N-acetylcysteine (NAC) in rats. Methodology: Male albino rats were randomly divided into 6 groups: untreated rats (control), rats orally treated with whey protein (1g/kg b.w/day) for seven executive days, rats treated orally with N-acetylcysteine (500 mg/kgb.w /day) for seven executive days, rates intoxicated intraperitoneal (ip) with cis- platin (10 mg/kgb.w. once), rats treated with whey protein (1g/kgb.w./day) for seven executive days) followed by one injection (ip) of cis-platin(10 mg/kg b.w.) one hour after the last oral administration of whey protein, rats treated with N- acetylcysteine (for seven executive days followed by one injection (ip) of cis-platin (10 mg/kgb.w) one hour after the last oral administration of N-acetylcysteine. The organ of Corti, the stria vascularis and spiral ganglia were visualized by light microscopy at different magnifications. Results: Cis-platin intoxicated animals showed a significant decrease in serum level of total antioxidant capacity (TAC),with inhibition in the activity of serum glutathione-s transferase(GST) and paraoxonnase-1 (PON-1) in comparison with control. Group treated with either NAC or WP with cis-platin showed significant elevation in the activity of both GST & PON-1 with increased serum level of TAC when compared with cis-platin intoxicated rats. Animals treated with NAC or WP with cis-platin compared to those treated with cis-platin alone showed marked degree of improvement towards control rats as there was significant drop in the serum level of cortecosterone, nitric oxide (NO), and melandialdehyde (MDA).Histopathologic, in NAC pretreated group there was no changes in stria vascularis or spiral ganglia. In group pretreated with WP, there was no histopathologic alteration detected in the organ of Corti and Reissers membrane but oedema and haemorrhage were founded in the stria vascularis in small focal manner. Conclusion: Our finding showed that Whey protein is a natural dietary supplement product proved its ability of protection of anti-oxidant system and the cochlea against cis-platin induced ototoxicity.

Keywords: anti-oxidant, cis-platin, N-acetylcysteine, ototoxicity, whey protein

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Authors: Kalpana Rajouriya, Ajay Taneja

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The objective of the present study is to investigate the regional and lobar deposition of size-segregated PM in respiratory tract of human body. PM in different fractions is monitored using the Grimm portable environmental dust monitor during winter season in Firozabad; a Glass city of India. PM10 concentration (200.817g/m³) was 4.46 and 2.0 times higher than the limits prescribed by WHO (45g/m⁻³) and NAAQS (100g/m⁻³) government agencies. PM2.5 concentration (83.538 g/m3) was 5.56 and 1.39 times higher from WHO (15g/m-3) and NAAQS (60g/m⁻³) limits. Results inferred that PM10 and PM2.5 was highest deposited in head region (0.3477-0.5622 & 0.366-0.4704) followed by pulmonary region, especially in the 9-21year old persons. The variation in deposition percentage in our study is mainly due to the airway geometry, PM size, and its deposition mechanisms. The coarse fraction, due to its large size, cannot follow the airway path and mostly gets deposited by inertial impaction in the head region and its bifurcations. The present study results inferred that Coarse and fine PM deposition was highly visualized in 9 (8.45610⁻⁴ g, 2.91110⁻⁴g) year and 3 (1.49610⁻⁴ g, 8.59310⁻⁵g) month age category. So, the 9year children and 3month infants category have high level of health risk.

Keywords: particulate matter, MPPD model, regional deposition, lobar deposition, health risk

Procedia PDF Downloads 31

Authors: C. Nathanailides, S. Anastasiou, P. Logothetis, G. Kanlis

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Production parameters of gilt head sea bream fish farm such as feeding regimes, mortalities, fish densities were used to calculate the economic efficiency of six different aquaculture sites from West Greece. Samples of farmed sea bream were collected and lipid content, microbial load and filleting yield of the samples were used as quality criteria. The results indicate that Lipid content, filleting yield and microbial load of fish originating from different fish farms varied significantly with improved quality exhibited in fish farms which exhibited improved Feed conversion rates and lower mortalities. Changes in feeding management practices such as feed quality and feeding regimes have a significant impact on the financial performance of sea bass farms. Fish farms which exhibited improved feeding conversion rates also exhibited increased profitability. Improvements in the FCR explained about 13.4 % of the difference in profitability of the different aquaculture sites. Lower mortality and higher growth rates were also exhibited by the fish farms which exhibited improved FCR. It is concluded that best feeding management practices resulted in improved product quality and profitability.

Keywords: aquaculture economics, gilt head sea, production fish, feeding management

Procedia PDF Downloads 480

Authors: YingWei Tan, XueFeng Ding

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Attention-based voice activity detection models have gained significant attention in recent years due to their fast training speed and ability to capture a wide contextual range. The inclusion of multi-head style and position embedding in the attention architecture are crucial. Having multiple attention heads allows for differential focus on different parts of the sequence, while position embedding provides guidance for modeling dependencies between elements at various positions in the input sequence. In this work, we propose an approach by considering each head as a node, enabling the application of graph neural networks (GNN) to identify correlations among the different nodes. In addition, we adopt an implementation named rotary position embedding (RoPE), which encodes absolute positional information into the input sequence by a rotation matrix, and naturally incorporates explicit relative position information into a self-attention module. We evaluate the effectiveness of our method on a synthetic dataset, and the results demonstrate its superiority over the baseline CRNN in scenarios with low signal-to-noise ratio and noise, while also exhibiting robustness across different noise types. In summary, our proposed framework effectively combines the strengths of CNN and RNN (LSTM), and further enhances detection performance through the integration of graph neural networks and rotary position embedding.

Keywords: voice activity detection, CRNN, graph neural networks, rotary position embedding

Procedia PDF Downloads 36

Authors: Mustafa Metin Donma

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Metabolic syndrome (MetS) components are noteworthy among children with obesity and morbid obesity because they point out the cases with MetS, which have the great tendency to severe health problems such as cardiovascular diseases both in childhood and adulthood. In clinical practice, considerable efforts are being observed to bring into the open the striking differences between morbid obese cases and those with MetS findings. The most privileged aspect is concerning cardiometabolic features. The aim of this study was to derive an index which behaves different in children with and without MetS from the cardiac point of view. For the purpose, aspartate transaminase (AST), a cardiac enzyme still being used independently to predict cardiac-related problems, was used. One hundred and twenty four children were recruited from the outpatient clinic of Department of Pediatrics in Tekirdag Namik Kemal University, Faculty of Medicine. Forty-three children with normal body mass index, forty-one and forty morbid obese (MO) children with MetS and without the characteristic features of MetS, respectively, were included in the study. Weight, height, waist circumference (WC), hip C (HC), head C (HdC), neck C (NC), systolic and diastolic blood pressure values were measured and recorded. Body mass index and anthropometric ratios were calculated. Fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein cholesterol (HDL-C) analyses were performed. The values for AST, alanin transaminase (ALT) and AST/ALT were obtained. Advanced Donma cardiac index (ADCI) values were calculated. The formula for the index was [(TRG/HDL-C) * (INS/FBG)] * [(WC+HC)/Height] * [(HdC+NC)/Height]. Statistical evaluations including correlation analysis were done by a statistical package program. The statistical significance degree was accepted as p<0.05. The index, ADCI, was developed from both anthropometric and biochemical parameters. All anthropometric measurements except weight were included in the equation. Besides all biochemical parameters concerning MetS components were also added. This index was tested in each of three groups. Its performance was compared with the performance of cardiometabolic index (CMI). It was also checked whether it was compatible with AST activity. The performance of ADCI was better than that of CMI. Instead of double increase, the increase of three times was observed in children with MetS compared to MO children. The index was correlated with AST in MO group and with AST/ALT in MetS group. In conclusion, this index was superior in discovering cardiac problems in MO and in diagnosing MetS in MetS groups. It was also arbiter to point out cardiovascular and MetS aspects among the groups.

Keywords: aspartate transaminase, cardiac, children, index, obesity

Procedia PDF Downloads 36

Authors: Çağla Aras, Kübra Bi̇nay, Aysberg Şamil önlü, Mine Baydan Aran, Dicle Aras

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The purpose of the present research was to investigate the acute effects of 30-min hatha yoga and 30-min resistance-based aerobic exercise (RBAE) on computerized dynamic posturography (CDP) and functional head impulse test (fHIT) scores in adult female yoga practitioners. To reach this aim, ten participants executed CDP and fHIT three times in total: at rest, after yoga, and after RBAE. The yoga practice lasted a total of 30 minutes, including 25 min of asanas and 5 minutes of savasana. RBAE lasted a total of 30 minutes with an intensity of 70-75% of the heart rate reserve method. When the results were examined, no change was observed in any parameters of the fHIT scores due to resting or exercise implementation. On the contrary, some changes were observed in CDP test results depending on the type of exercise. The post-RBAE somatosensory and visual systems values were higher than resting (p<0.05). The composite balance score derived after RBAE was found to be improved when compared to post-yoga and resting values (p<0.01). Lastly, the post-RBAE vestibular system score was found to be statistically significantly higher than the post-Yoga values. In addition, it was observed that body composition parameters, especially decreasing BW, LBM, PBF, MBF and TBW, were associated with improved postural stability values. According to the results, it can be stated that neither hatha yoga nor resistance-based aerobic exercise has an acute effect on functional vestibulo-ocular reflex. In addition, although there was no change in balance level after yoga, it was observed that RBAE performed at 70-75% of the heart rate reserve and for 30 minutes had positive acute effects on postural stability and balance.

Keywords: hatha yoga, resistance training, aerobic training, high intensity training, computerized dynamic posturography, functional head impulse test

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Authors: Ione Loots, Marco van Dijk, Jay Bhagwan

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Historically, South Africa had various small-scale hydropower installations in remote areas that were not incorporated in the national electricity grid. Unfortunately, in the 1960s most of these plants were decommissioned when Eskom, the national power utility, rapidly expanded its grid and capability to produce cheap, reliable, coal-fired electricity. This situation persisted until 2008, when rolling power cuts started to affect all citizens. This, together with the rising monetary and environmental cost of coal-based power generation, has sparked new interest in small-scale hydropower development, especially in remote areas or at locations (like wastewater treatment works) that could not afford to be without electricity for long periods at a time. Even though South Africa does not have the same, large-scale, hydropower potential as some other African countries, significant potential for micro- and small-scale hydropower is hidden in various places. As an example, large quantities of raw and potable water are conveyed daily under either pressurized or gravity conditions over large distances and elevations. Due to the relative water scarcity in the country, South Africa also has more than 4900 registered dams of varying capacities. However, institutional capacity and skills have not been maintained in recent years and therefore the identification of hydropower potential, as well as the development of micro- and small-scale hydropower plants has not gained significant momentum. An assessment model and decision support system for low head hydropower development has been developed to assist designers and decision makers with first-order potential analysis. As a result, various potential sites were identified and many of these sites were situated at existing infrastructure like weirs, barrages or pipelines. One reason for the specific interest in existing infrastructure is the fact that capital expenditure could be minimized and another is the reduced negative environmental impact compared to greenfield sites. This paper will explore the case study of retrofitting an unconventional and innovative hydropower plant to the outlet of a wastewater treatment works in South Africa.

Keywords: low head hydropower, retrofitting, small-scale hydropower, wastewater treatment works

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Authors: Zehra Aytac, Nurdilek Gulmezoglu

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Safflower has been grown for centuries for many purposes worldwide. Especially it is important for the orange-red dye from its petal and for its high-quality oil obtained from the seeds. The crop is high adaptable to areas with insufficient rainfall and poor soil conditions. The plant has a deep taproot that can draw moisture and plant nutrients from deep to the subsoil. The research was carried out to study the nitrogen (N) uptake of different safflower cultivars and lines at different stages of growth and different plant parts in the experimental field of Faculty of Agriculture, Eskişehir Osmangazi University under semi-arid conditions. Different safflower cultivars and lines of varied origins were used as the material. The cultivars and lines were planted in a Randomized Complete Block Design with three replications. Two different growth stages (flowering and harvest) and three different plant parts (head, stem+leaf and seed) were determined. The nitrogen concentration of different plant parts was determined by the Kjeldahl method. Statistical analysis were performed by analysis of variance for each growth stage and plant parts taking a level of p < 0.05 and p < 0.01 as significant according to the LSD test. As a result, N concentration showed significant differences among different plant parts and different growth stages for different safflower genotypes of varied origins.

Keywords: Carthamus tinctorius L., growth stages, head N, leaf N, N uptake, seed N, Safflower

Procedia PDF Downloads 196

Authors: Aleksandra Zysk, Pawel Badura

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Recognizing and controlling vocal registers during singing is a difficult task for beginner vocalist. It requires among others identifying which part of natural resonators is being used when a sound propagates through the body. Thus, an application has been designed allowing for sound recording, automatic vocal register recognition (VRR), and a graphical user interface providing real-time visualization of the signal and recognition results. Six spectral features are determined for each time frame and passed to the support vector machine classifier yielding a binary decision on the head or chest register assignment of the segment. The classification training and testing data have been recorded by ten professional female singers (soprano, aged 19-29) performing sounds for both chest and head register. The classification accuracy exceeded 93% in each of various validation schemes. Apart from a hard two-class clustering, the support vector classifier returns also information on the distance between particular feature vector and the discrimination hyperplane in a feature space. Such an information reflects the level of certainty of the vocal register classification in a fuzzy way. Thus, the designed recognition and training application is able to assess and visualize the continuous trend in singing in a user-friendly graphical mode providing an easy way to control the vocal emission.

Keywords: classification, singing, spectral analysis, vocal emission, vocal register

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Authors: Naum Simanovsky MD, Michael Zaidman MD, Vladimir Goldman MD.

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105 plain AP radiographs of normal adult pelvises (210 hips) were evaluated. Different measurements of normal and dysplastic hip joints in 45 patients were analyzed. Attempt was made to establish reproducible, easy applicable in practice approach for evaluation and follow up of patients with hip dysplasia. The youngest of our patients was 11 years and the oldest was 47 years. Only one of our patients needed conversion to total hip replacement (THR) during ten years of follow-up. It was emphasized that selected set of measurements was built for purpose to serve, especially those who’s scheduled or undergone PAO. This approach was based on concept of acetabulum-femoral head complex and importance of reliable reference points of measurements. Comparative analysis of measured parameters between normal and dysplastic hips was performed. Among 10 selected parameters, we use already well established such as lateral center edge angle and head extrusion index, but to serve specific group of patients with PAO, new parameters were considered such as complex lateralization and complex proximal migration. By our opinion proposed approach is easy applicable in busy clinical practice, satisfactorily delineate hip pathology and give to surgeon who’s going to perform PAO guidelines in condensed form. It is also useful tools for postoperative follow up after PAO.

Keywords: periacetabular osteotomy, plain radiograph’s measurements, adolescents, adult

Procedia PDF Downloads 42

Authors: Gabriella Jorge, Carlos A. Pérez, Hanna Friberg, Sara Söderlund, Jan Lagerlöf

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Fusarium Head Blight (FHB) is one of the most important Fusarium-caused diseases, which affects cereals with serious detrimental effects on yield and grain quality worldwide. Earthworms have been suggested as an alternative to control this disease, which requires a combination of preventive methods to reduce level of damage, although it has been proven that their effect is species dependent. Our objective was to evaluate the effect of the earthworms Aporrectodea longa and Lumbricus rubellus, on the inoculum of Fusarium graminearum on wheat straw. To test this we kept earthworms in vessels with soil, and F. graminearum-inoculated straw covering the surface, under controlled conditions for 6 weeks. Two factors were evaluated with a complete factorial design: earthworms (three levels: without earthworms, A. longa, and L. rubellus), and straw (two levels: inoculated with the pathogen, and sterile). The presence of L. rubellus significantly (P<0.05) reduced the amount of inoculated straw at the soil surface 31% after 6 weeks, while the presence of A. longa, most found in quiescence, did not have any significant effect on the amount of straw when compared to the control. After incubation, F. graminearum was detected by qPCR, only in the surface straw in those treatments inoculated with the pathogen but without earthworms. None of the treatments showed presence of Fusarium in the buried straw, soil or earthworm casts. Both earthworm species decreased in body weight during incubation, most likely due to the decrease in soil water content during the experiment, from 25% to 20%, and/or inadequate food supply, since no other source of food was added. However, this reduction in weight occurred indistinctly of the presence or not of Fusarium (P<0.05). This indicates that both species, of different ecological groups, anecic and epigeic, can reduce F. graminearum inoculum present in wheat straw, while their growth is not negatively affected by this pathogen. These promising results place A. longa, and L. rubellus as potential biocontrol agents of this fungal plant pathogen responsible for Fusarium Head Blight disease in wheat, although further ongoing experiments are needed to confirm the repeatability of these results.

Keywords: Aporrectodea longa, biological control, fungal plant pathogen, Lumbricus rubellus, qPCR, wheat straw

Procedia PDF Downloads 249

Authors: Niyti, Aman Deep, Rajesh Kharab, Sahila Chopra, Raj. K. Gupta

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Relatively long-lived transactinide elements (i.e., elements with atomic number Z≥104) up to Z = 108 have been produced in nuclear reactions between low Z projectiles (C to Al) and actinide targets. Cross sections have been observed to decrease steeply with increasing Z. Recently, production cross sections of several picobarns have been reported for comparatively neutron-rich nuclides of 112 through 118 produced via hot fusion reactions with 48Ca and actinide targets. Some of those heavy nuclides are reported to have lifetimes on the order of seconds or longer. The relatively high cross sections in these hot fusion reactions are not fully understood and this has renewed interest in systematic studies of heavy-ion reactions with actinide targets. The main aim of this work is to understand the dynamics hot fusion reactions 18O+ 248Cm and 22Ne+244Pu (carried out at RIKEN and TASCA respectively) using the collective clusterization technique, carried out by undertaking the decay of the compound nucleus 266Rf∗ into 4n, 5n and 6n neutron evaporation channels. Here we extend our earlier study of the excitation functions (EFs) of 266Rf∗, formed in fusion reaction 18O+248Cm, based on Dynamical Cluster-decay Model (DCM) using the pocket formula for nuclear proximity potential, to the use of other nuclear interaction potentials derived from Skyrme energy density formalism (SEDF) based on semiclassical extended Thomas Fermi (ETF) approach and also study entrance channel effects by considering the synthesis of 266Rf* in 22Ne+244Pu reaction. The Skyrme forces used are the old force SIII, and new forces GSkI and KDE0(v1). Here, the EFs for the production of 260Rf, 261Rf and 262Rf isotope via 6n, 5n and 4n decay channel from the 266Rf∗ compound nucleus are studied at Elab = 88.2 to 125 MeV, including quadrupole deformations β2i and ‘hot-optimum’ orientations θi. The calculations are made within the DCM where the neck-length ∆R is the only parameter representing the relative separation distance between two fragments and/or clusters Ai which assimilates the neck formation effects.

Keywords: entrance channel effects, fusion reactions, skyrme force, superheavy nucleus

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Authors: Mir Afzal Tajik

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The 'Strengthening Teacher Education in Pakistan' (STEP) is an innovative programme jointly funded by the Government of Canada and the Aga Khan Foundation Canada and implemented by the Aga Khan University - Institute for Educational Development (AKU-IED) in partnership with the local governments, education departments and communities in the provinces of Balochistan, Sindh and Gilgit-Baltistan in Pakistan. One of the key components of the programme is professional development of teachers, head teachers and teacher educators through a variety of teacher education programmes including a two-year Masters of Education (MEd) Programme offered by AKU-IED. A number of teachers, head teachers and teacher educators from these provinces have been developed through the MEd Programme. This paper discusses a qualitative research study conducted to explore the nature, relevance, rigor and richness of the experiences of the MEd graduates, and how these experiences have fostered their own professional development and their ability to bring about positive changes in their schools. The findings of the study provide useful insights into the graduates’ self-actualization, transformation of their professional beliefs and practices, the difference they have made in their schools, and the challenges they face. The study also provides evidences of how the implementation of this multi-stakeholders and multi-partners STEP programme has led to the development of ‘communities of practice’ in schools. The study then makes a number of recommendations for policy and practice related to teacher education programmes as well as for partnerships in education.

Keywords: STEP, change agents, Pakistan, Canada, teacher education, MEd

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Authors: Taku Numao, Kazu Amimoto, Tomoko Shimada, Kyohei Ichikawa

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Background: Unilateral spatial neglect (USN) is a common syndrome following damage to one hemisphere of the brain (usually the right side), in which a patient fails to report or respond to stimulation from the contralesional side. These symptoms are not due to primary sensory or motor deficits, but instead, reflect an inability to process input from that side of their environment. Prism adaptation (PA) is a therapeutic treatment for USN, wherein a patient’s visual field is artificially shifted laterally, resulting in a sensory-motor adaptation. However, patients with USN also tend to perceive a left-leaning subjective vertical in the frontal plane. The traditional PA cannot be used to correct a tilt in the subjective vertical, because a prism can only polarize, not twist, the surroundings. However, this can be accomplished using a head mounted display (HMD) and a web-camera. Therefore, this study investigated whether an HMD system could be used to correct the spatial perception of USN patients in the frontal as well as the horizontal plane. We recruited healthy subjects in order to collect data for the refinement of USN patient therapy. Methods: Eight healthy subjects sat on a chair wearing a HMD (Oculus rift DK2), with a web-camera (Ovrvision) displaying a 10 degree leftward rotation and a 10 degree counter-clockwise rotation along the frontal plane. Subjects attempted to point a finger at one of four targets, assigned randomly, a total of 48 times. Before and after the intervention, each subject’s body-centre judgment (BCJ) was tested by asking them to point a finger at a touch panel straight in front of their xiphisternum, 10 times sight unseen. Results: Intervention caused the location pointed to during the BCJ to shift 35 ± 17 mm (Ave ± SD) leftward in the horizontal plane, and 46 ± 29 mm downward in the frontal plane. The results in both planes were significant by paired-t-test (p<.01). Conclusions: The results in the horizontal plane are consistent with those observed following PA. Furthermore, the HMD and web-camera were able to elicit 3D effects, including in both the horizontal and frontal planes. Future work will focus on applying this method to patients with and without USN, and investigating whether subject posture is also affected by the HMD system.

Keywords: head mounted display, posture, prism adaptation, unilateral spatial neglect

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Authors: Anindita Patra, Prasad K. Bhaskaran

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The atmosphere-ocean is a dynamically linked system that influences the exchange of energy, mass, and gas at the air-sea interface. The exchange of energy takes place in the form of sensible heat, latent heat, and momentum commonly referred to as fluxes along the atmosphere-ocean boundary. The large scale features such as El Nino and Southern Oscillation (ENSO) is a classic example on the interaction mechanism that occurs along the air-sea interface that deals with the inter-annual variability of the Earth’s Climate System. Most importantly the ocean and atmosphere as a coupled system acts in tandem thereby maintaining the energy balance of the climate system, a manifestation of the coupled air-sea interaction process. The present work is an attempt to understand the long-term variability in atmospheric parameters (from surface to upper levels) and investigate their role in influencing the surface ocean variables. More specifically the influence of atmospheric circulation and its variability influencing the mean Sea Level Pressure (SLP) has been explored. The study reports on a critical examination of both ocean-atmosphere parameters during a monsoon season over the head Bay of Bengal region. A trend analysis has been carried out for several atmospheric parameters such as the air temperature, geo-potential height, and omega (vertical velocity) for different vertical levels in the atmosphere (from surface to the troposphere) covering a period from 1992 to 2012. The Reanalysis 2 dataset from the National Centers for Environmental Prediction-Department of Energy (NCEP-DOE) was used in this study. The study signifies that the variability in air temperature and omega corroborates with the variation noticed in geo-potential height. Further, the study advocates that for the lower atmosphere the geo-potential heights depict a typical east-west contrast exhibiting a zonal dipole behavior over the study domain. In addition, the study clearly brings to light that the variations over different levels in the atmosphere plays a pivotal role in supporting the observed dipole pattern as clearly evidenced from the trends in SLP, associated surface wind speed and significant wave height over the study domain.

Keywords: air temperature, geopotential height, head Bay of Bengal, long-term variability, NCEP reanalysis 2, omega, wind-waves

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Authors: A. Haddick, A. Soltan

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Background: During the period of recovery from an operative obstetric procedure, a woman is not only at risk of the life-threatening complications accompanying labour but also those associated with surgery and anaesthesia. It is speculated that women in the recovery area may receive a lower standard of care over a night shift. Thus obstetric recovery room care should be evaluated regularly to ensure all women receive an equally high standard of care 24/7. Aim: The aim of this audit was to undertake an audit in the Liverpool Women’s Hospital on the care in recovery, and to ascertain the extent to which the standards were met. This audit included the full audit cycle. Method: Standards were taken from the AAGBI, RCOA, NICE and CNST guidelines. There were 12 standards including appropriate documentation of vital signs and appropriate length of stay after surgery. Notes from 100 patients were analysed from March 2011-March 2012. There were 52 day notes and 48 night notes; these were accessed to gain the relevant data. In the re audit 35 notes were accessed from March 14-September 14. Results: The Liverpool Women’s Hospital met in total 10 of these standards. 10 were met during the day shift (83%) and 0 met during the night shift. In the re audit, there was a significant improvement in the standards met at night. 9 of the standards were met during the day and 7 of the standards were met at night. Clearly there are still improvements to be made. Conclusions: In the original audit, an audit action plan was formulated. This was following discussion of the results of this audit in an MDT meeting and presentation with a consultant Obstetrician, the head of Midwifery, the head of Obstetrics theatres and a recovery nurse. This audit will be further discussed in the Liverpool Woman's Hospital in July 2015 for further implementation for improvement.

Keywords: care, recovery, room, women

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Authors: Suparmi, Sampurna

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Sodium nitrite which is widespread used as a color fixative and preservative in foods can increase oxidative stress and cause hemolytic anemia. Consumption of food supplement containing sufficient antioxidant, e.g. chlorophyll, reported can decrease these negative effects. This study was conducted to determine the effect of chlorophyll from Sauropus androgynus leaves on Malodialdehide (MDA) and ferritin level. Experimental research with post-test only control group design was conducted using 24 female mice strain Balb-c. Sodium nitrite 0.3 ml/head/day given during 18 days, while the chlorophyll or Cu-chlorophyllin as much as 0.7 ml/head/day given the following day for 14 days. The mean of MDA levels of blood plasma in the control group, NaNO2 induction, induction NaNO2 and chlorophyll of S. androgynus leaves, induction of NaNO2 and Cu-chlorophyllin from K-Liquid in sequence is 2.10±0.11mol/L, 3.44±0.38 mol/L, 2.31±0.18 mol/L, 2.31±0.13 mol/L, whilst the ferritin levels mean in each group is 62.71±6.42 ng/ml; 63.22±7.59 ng/ml; 67.45±8.03 ng/ml, and 64.74±7.80 ng/ml, respectively. Results of Mann Whitney test found no significant difference in MDA levels (p>0.05), while the One-Way Anova test result found no significant difference in ferritin levels between the groups of mice that received S. androgynus chlorophyll with a group of mice that received Cu-chlorophyllin after induction NaNO2 (p>0.05). This indicates that chlorophyll from S. androgynus leaves as effective as Cu-chlorophyllin in decrease of MDA levels and increase of ferritin levels. Chlorophyll from S. androgynus are potential as food supplement in anemic conditions caused by sodium nitrite consumptions.

Keywords: ferritin, MDA, chlorophyll, sodium nitrite

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Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher

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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.

Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping

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Authors: D: Gupta, M. Radhakrishnan, Y. Kurhe, D. Thangaraj

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Depression is among the leading causes of death worldwide. The current pharmacotherapy is associated with poor compliance, resistance and relapse, which necessitate the development of novel compounds with better efficacy. The present study designed and synthesized EQC-34 (N-cyclohexyl-3-ethoxyquinoxalin-2-carboxamide) as novel serotonin type-3 (5HT3) antagonist and evaluated its antidepressant-like effects using neurobehavioral mouse model. 5HT3 antagonism (as pA2 value) was determined on the longitudinal smooth muscle of guinea-pig ileum against 2-methyl-5HT (a 5HT3 agonist). The doses were calculated by dose response of basal locomotor activity. Consequently, effects of EQC-34 on neurobehavioral parameters were measured in forced swim (FST) and tail suspension test (TST). The possible mechanism was estimated by interaction study with fluoxetine (a selective serotonin reuptake inhibitor) and mCPBG (1-(m-chlorophenyl)-biguanide, a selective 5HT3 agonist), and confirmed by potentiation of head twitch response by 5hydroxy-L-tryptophan (5HTP). EQC-34 (1-4 mg/kg, i.p.) produced significant decreased behavioral despair effects in FST and TST. It potentiated fluoxetine response, while mCPBG reduced EQC-34 activity in FST. Further, EQC-34 potentiated 5HTP induced head twitch response. EQC-34 revealed potential antidepressant-like effects, which may involve 5HT3 receptor mediated facilitation of 5HT neurotransmission, thereby reversing the pathological deficiency of monoamines (5HT) observed in depression. Thus, it may be further investigated as promising agent to improve therapeutics of depression.

Keywords: depression, forced swim test, 5HT3 receptor antagonist, serotonin

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Authors: Raj Chandran, Saul Datwyler, Jaime Marino, Daniel West, Karla Grasso, Adam Buss, Hina Syed, Zina Al Sahouri, Jennifer Yen, Krista Caudle, Beth McQuiston

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The Alinity i TBI test is Therapeutic Goods Administration (TGA) registered and is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays for the measurement of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) in plasma and serum. The Alinity i TBI performance was evaluated in a multi-center pivotal study to demonstrate the capability to assist in determining the need for a CT scan of the head in adult subjects (age 18+) presenting with suspected mild TBI (traumatic brain injury) with a Glasgow Coma Scale score of 13 to 15. TBI has been recognized as an important cause of death and disability and is a growing public health problem. An estimated 69 million people globally experience a TBI annually1. Blood-based biomarkers such as glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) have shown utility to predict acute traumatic intracranial injury on head CT scans after TBI. A pivotal study using prospectively collected archived (frozen) plasma specimens was conducted to establish the clinical performance of the TBI test on the Alinity i system. The specimens were originally collected in a prospective, multi-center clinical study. Testing of the specimens was performed at three clinical sites in the United States. Performance characteristics such as detection limits, imprecision, linearity, measuring interval, expected values, and interferences were established following Clinical and Laboratory Standards Institute (CLSI) guidance. Of the 1899 mild TBI subjects, 120 had positive head CT scan results; 116 of the 120 specimens had a positive TBI interpretation (Sensitivity 96.7%; 95% CI: 91.7%, 98.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%; 95% CI: 37.8, 42.4). The negative predictive value (NPV) of the test was 99.4% (713/717, 95% CI: 98.6%, 99.8%). The analytical measuring interval (AMI) extends from the limit of quantitation (LoQ) to the upper LoQ and is determined by the range that demonstrates acceptable performance for linearity, imprecision, and bias. The AMI is 6.1 to 42,000 pg/mL for GFAP and 26.3 to 25,000 pg/mL for UCH-L1. Overall, within-laboratory imprecision (20 day) ranged from 3.7 to 5.9% CV for GFAP and 3.0 to 6.0% CV for UCH-L1, when including lot and instrument variances. The Alinity i TBI clinical performance results demonstrated high sensitivity and high NPV, supporting the utility to assist in determining the need for a head CT scan in subjects presenting to the emergency department with suspected mild TBI. The GFAP and UCH-L1 assays show robust analytical performance across a broad concentration range of GFAP and UCH-L1 and may serve as a valuable tool to help evaluate TBI patients across the spectrum of mild to severe injury.

Keywords: biomarker, diagnostic, neurology, TBI

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Authors: Yin-Hsuan Wu, Perng-Jy Tsai, Ying-Fang Wang, Shun-Hui Chung

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The present study was conducted to characterize exposure concentrations, concentrations deposited on the different respiratory regions, and resultant health risks associated with heavy metal exposures for road marking workers. Road marking workers of three similar exposure groups (SEGs) were selected, including the paint pouring worker, marking worker, and preparing worker. Personal exposure samples were collected using an inhalable dust sampler (IOM), and the involved particle size distribution samples were estimated using an eight-stage Marple personal cascade impactor during five working days. In total, 25 IOM samples and 20 Marple samples were collected. All collected samples were analyzed for their heavy metal contents using the ICP/MS. The resultant heavy metal particle size distributions were also used to estimate the fractions of particle deposited on the head airways (Chead), tracheobronchial (Cthorac) and alveolar regions (Cresp) of the exposed workers. In addition, Pb and Cr were selected to estimate the incremental cancer risk, and Zn, Ti, and Mo were selected to estimate the corresponding non-cancer risk in the present study. Results show that three heavy metals, including Pb, Cr, and Ti, were found with the highest concentrations for the SEG of the paint pouring worker (=0.585±2.98, 0.307±1.71, 0.902±2.99 μg/m³, respectively). For the fraction of heavy metal particle deposited on the respiratory tract, both alveolar and head regions were found with the highest values (=23-43% and 39-61%, respectively). For both SEGs of the paint pouring and marking, 51% of Cr, 59-61% of Zn, and 48-51% of Ti were found to be deposited on the alveolar region, and 41-43% of Pb was deposited on the head region. Finally, the incremental cancer risk for the SEGs of the paint pouring, marking, and preparing were found as 1.08×10⁻⁵, 2.78×10⁻⁶, and 2.20×10⁻⁶, respectively. In addition, the estimated non-cancer risk for the above three SEGs was found to be consistently less than unity. In conclusion, though the estimated non-cancer risk was less than unity, all resultant incremental cancer risk was greater than 10⁻⁶ indicating the abatement of workers’ exposure is necessary. It is suggested that strategies, including placing on the molten kettle, substitution the currently used paints for less heavy metal containing paints, and wearing fume protecting personal protective equipment can be considered in the future from reducing the worker’s exposure aspect.

Keywords: health risk assessment, heavy metal, respiratory track deposition, road marking

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Authors: Asma Poursoroush

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Solid-supported lipid bilayers are often used as a simple model for studies of biological membranes. The presence of a solid substrate that interacts attractively with lipid head-groups is expected to affect the phase behavior of the supported bilayer. Molecular dynamics simulations of a coarse-grained model are thus performed to investigate the phase behavior of supported one-component lipid bilayer membranes. Our results show that the attraction of the lipid head groups to the substrate leads to a phase behavior that is different from that of a free standing lipid bilayer. In particular, we found that the phase behaviors of the two leaflets are decoupled in the presence of a substrate. The proximal leaflet undergoes a clear gel-to-fluid phase transition at a temperature lower than that of a free standing bilayer, and that decreases with increasing strength of the substrate-lipid attraction. The distal leaflet, however, undergoes a change from a homogeneous liquid phase at high temperatures to a heterogeneous state consisting of small liquid and gel domains, with the average size of the gel domains that increases with decreasing temperature. While the chain order parameter of the proximal leaflet clearly shows a gel-fluid phase transition, the chain order parameter of the distal leaflet does not exhibit a clear phase transition. The decoupling in the phase behavior of the two leaflets is due to a non-symmteric lipid distribution in the two leaflets resulting from the presence of the substrate.

Keywords: membrane, substrate, molecular dynamics, simulation

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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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