Search results for: experience sampling methods

Authors: B. S. Premalatha, Kausalya Sahani

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Background: Glomus jugulare tumors arise within the jugular foramen and are commonly seen in females particularly on the left side. Surgical excision of the tumor may cause lower cranial nerve deficits. Cranial nerve involvement produces hoarseness of voice, slurred speech, and dysphagia along with other physical symptoms, thereby affecting the quality of life of individuals. Though oncological clearance is mainly emphasized on while treating these individuals, little importance is given to their communication, voice and swallowing problems, which play a crucial part in daily functioning. Objective: To examine the functions of voice, speech and swallowing outcomes of the subjects, following excision of glomus jugulare tumor. Methods: Two female subjects aged 56 and 62 years had come with a complaint of change in voice, inability to swallow and reduced clarity of speech following surgery for left glomus jugulare tumor were participants of the study. Their surgical information revealed multiple cranial nerve palsies involving the left facial, left superior and recurrent branches of the vagus nerve, left pharyngeal, left soft palate, left hypoglossal and vestibular nerves. Functional outcomes of voice, speech and swallowing were evaluated by perceptual and objective assessment procedures. Assessment included the examination of oral structures and functions, dysarthria by Frenchey dysarthria assessment, cranial nerve functions and swallowing functions. MDVP and Dr. Speech software were used to evaluate acoustic parameters of voice and quality of voice respectively. Results: The study revealed that both the subjects, subsequent to excision of glomus jugulare tumor, showed a varied picture of affected oral structure and functions, articulation, voice and swallowing functions. The cranial nerve assessment showed impairment of the vagus, hypoglossal, facial and glossopharyngeal nerves. Voice examination indicated vocal cord paralysis associated with breathy quality of voice, weak voluntary cough, reduced pitch and loudness range, and poor respiratory support. Perturbation parameters as jitter, shimmer were affected along with s/z ratio indicative of voice fold pathology. Reduced MPD(Maximum Phonation Duration) of vowels indicated that disturbed coordination between respiratory and laryngeal systems. Hypernasality was found to be a prominent feature which reduced speech intelligibility. Imprecise articulation was seen in both the subjects as the hypoglossal nerve was affected following surgery. Injury to vagus, hypoglossal, gloss pharyngeal and facial nerves disturbed the function of swallowing. All the phases of swallow were affected. Aspiration was observed before and during the swallow, confirming the oropharyngeal dysphagia. All the subsystems were affected as per Frenchey Dysarthria Assessment signifying the diagnosis of flaccid dysarthria. Conclusion: There is an observable communication and swallowing difficulty seen following excision of glomus jugulare tumor. Even with complete resection, extensive rehabilitation may be necessary due to significant lower cranial nerve dysfunction. The finding of the present study stresses the need for involvement of as speech and swallowing therapist for pre-operative counseling and assessment of functional outcomes.

Keywords: functional outcome, glomus jugulare tumor excision, multiple cranial nerve impairment, speech and swallowing

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Authors: S. MacDougall-Davis, S. Wysling, R. Willmore

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Background: The application of good non-technical skills, also known as crew resource management (CRM), is central to the delivery of safe, effective healthcare. The authors have been running remote trauma courses for over 10 years, primarily focussing on developing participants’ CRM in time-critical, high-stress clinical situations. The course has undergone an iterative process over the past 10 years. We employ a number of experiential learning techniques for improving CRM, including small group workshops, military command tasks, high fidelity simulations with reflective debriefs, and a ‘flipped classroom’, where participants are asked to create their own simulations and assess and debrief their colleagues’ CRM. We created a randomised simulation study to assess the impact of our course on UK medical students’ CRM, both at an individual and a teams level. Methods: Sixteen students took part. Four clinical scenarios were devised, designed to be of similar urgency and complexity. Professional moulage effects and experienced clinical actors were used to increase fidelity and to further simulate high-stress environments. Participants were block randomised into teams of 4; each team was randomly assigned to one pre-course simulation. They then underwent our 5 day remote trauma CRM course. Post-course, students were re-randomised into four new teams; each was randomly assigned to a post-course simulation. All simulations were videoed. The footage was reviewed by two independent CRM-trained assessors, who were blinded to the before/after the status of the simulations. Assessors used the internationally validated team emergency assessment measure (TEAM) to evaluate key areas of team performance, as well as a global outcome rating. Prior to the study, assessors had scored two unrelated scenarios using the same assessment tool, demonstrating 89% concordance. Participants also completed pre- and post-course questionnaires. Likert scales were used to rate individuals’ perceived NTS ability and their confidence to work in a team in time-critical, high-stress situations. Results: Following participation in the course, a significant improvement in CRM was observed in all areas of team performance. Furthermore, the global outcome rating for team performance was markedly improved (40-70%; mean 55%), thus demonstrating an impact at Level 4 of Kirkpatrick’s hierarchy. At an individual level, participants’ self-perceived CRM improved markedly after the course (35-70% absolute improvement; mean 55%), as did their confidence to work in a team in high-stress situations. Conclusion: Our study demonstrates that with a short, cost-effective course, using easily reproducible teaching sessions, it is possible to significantly improve participants’ CRM skills, both at an individual and, perhaps more importantly, at a teams level. The successful functioning of multi-disciplinary teams is vital in a healthcare setting, particularly in high-stress, time-critical situations. Good CRM is of paramount importance in these scenarios. The authors believe that these concepts should be introduced from the earliest stages of medical education, thus promoting a culture of effective CRM and embedding an early appreciation of the importance of these skills in enabling safe and effective healthcare.

Keywords: crew resource management, non-technical skills, training, simulation

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Authors: Rachael Andrews, Viktoria McMillan, Shuaib Nasser, Christopher M. Roberts

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Background and objective: The National Review of Asthma Deaths (NRAD) found that asthma management and care was inadequate in 26% of cases reviewed. Major shortfalls identified were adherence to national guidelines and standards and, particularly, the organisation of care, including supervision and monitoring in primary care, with 70% of cases reviewed having at least one avoidable factor in this area. 5.4 million people in the UK are diagnosed with and actively treated for asthma, and approximately 60,000 are admitted to hospital with acute exacerbations each year. The majority of people with asthma receive management and treatment solely in primary care. This has therefore created concern that many people within the UK are receiving sub-optimal asthma care resulting in unnecessary morbidity and risk of adverse outcome. NRAD concluded that a national asthma audit programme should be established to measure and improve processes, organisation, and outcomes of asthma care. Objective: To develop a primary care dataset enabling extraction of information from GP practices in Wales and providing robust data by which results and lessons could be drawn and drive service development and improvement. Methods: A multidisciplinary group of experts, including general practitioners, primary care organisation representatives, and asthma patients was formed and used as a source of governance and guidance. A review of asthma literature, guidance, and standards took place and was used to identify areas of asthma care which, if improved, would lead to better patient outcomes. Modified Delphi methodology was used to gain consensus from the expert group on which of the areas identified were to be prioritised, and an asthma patient and carer focus group held to seek views and feedback on areas of asthma care that were important to them. Areas of asthma care identified by both groups were mapped to asthma guidelines and standards to inform and develop primary and secondary care datasets covering both adult and pediatric care. Dataset development consisted of expert review and a targeted consultation process in order to seek broad stakeholder views and feedback. Results: Areas of asthma care identified as requiring prioritisation by the National Asthma Audit were: (i) Prescribing, (ii) Asthma diagnosis (iii) Asthma Reviews (iv) Personalised Asthma Action Plans (PAAPs) (v) Primary care follow-up after discharge from hospital (vi) Methodologies and primary care queries were developed to cover each of the areas of poor and variable asthma care identified and the queries designed to extract information directly from electronic patients’ records. Conclusion: This paper describes the methodological approach followed to develop primary care datasets for a National Asthma Audit. It sets out the principles behind the establishment of a National Asthma Audit programme in response to a national asthma mortality review and describes the development activities undertaken. Key process elements included: (i) mapping identified areas of poor and variable asthma care to national guidelines and standards, (ii) early engagement of experts, including clinicians and patients in the process, and (iii) targeted consultation of the queries to provide further insight into measures that were collectable, reproducible and relevant.

Keywords: asthma, primary care, general practice, dataset development

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Authors: Igor B. Sivaev

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Design of molecular machines is an extraordinary growing and very important area of research that it was recognized by awarding Sauvage, Stoddart and Feringa the Nobel Prize in Chemistry in 2016 'for the design and synthesis of molecular machines'. Based on the type of motion being performed, molecular machines can be divided into two main types: molecular motors and molecular switches. Molecular switches are molecules or supramolecular complexes having bistability, i.e., the ability to exist in two or more stable forms, among which may be reversible transitions under external influence (heating, lighting, changing the medium acidity, the action of chemicals, exposure to magnetic or electric field). Molecular switches are the main structural element of any molecular electronics devices. Therefore, the design and the study of molecules and supramolecular systems capable of performing mechanical movement is an important and urgent problem of modern chemistry. There is growing interest in molecular switches and other devices of molecular electronics based on transition metal complexes; therefore choice of suitable stable organometallic unit is of great importance. An example of such unit is bis(dicarbollide) complexes of transition metals [3,3’-M(1,2-C₂B₉H₁₁)₂]ⁿ⁻. The control on the ligand rotation in such complexes can be reached by introducing substituents which could provide stabilization of certain rotamers due to specific interactions between the ligands, on the one hand, and which can participate as Lewis bases in complex formation with external metals resulting in a change in the rotation angle of the ligands, on the other hand. A series of isomeric methyl sulfide derivatives of cobalt bis(dicarbollide) complexes containing methyl sulfide substituents at boron atoms in different positions of the pentagonal face of the dicarbollide ligands [8,8’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻, rac-[4,4’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ and meso-[4,7’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ were synthesized by the reaction of CoCl₂ with the corresponding methyl sulfide carborane derivatives [10-MeS-7,8-C₂B₉H₁₁)₂]⁻ and [10-MeS-7,8-C₂B₉H₁₁)₂]⁻. In the case of asymmetrically substituted cobalt bis(dicarbollide) complexes the corresponding rac- and meso-isomers were successfully separated by column chromatography as the tetrabutylammonium salts. The compounds obtained were studied by the methods of ¹H, ¹³C, and ¹¹B NMR spectroscopy, single crystal X-ray diffraction, cyclic voltammetry, controlled potential coulometry and quantum chemical calculations. It was found that in the solid state, the transoid- and gauche-conformations of the 8,8’- and 4,4’-isomers are stabilized by four intramolecular CH···S(Me)B hydrogen bonds each one (2.683-2.712 Å and 2.709-2.752 Å, respectively), whereas gauche-conformation of the 4,7’-isomer is stabilized by two intramolecular CH···S hydrogen bonds (2.699-2.711 Å). The existence of the intramolecular CH·S(Me)B hydrogen bonding in solutions was supported by the 1H NMR spectroscopy. These data are in a good agreement with results of the quantum chemical calculations. The corresponding iron and nickel complexes were synthesized as well. The reaction of the methyl sulfide derivatives of cobalt bis(dicarbollide) with various labile transition metal complexes results in rupture of intramolecular hydrogen bonds and complexation of the methyl sulfide groups with external metal. This results in stabilization of other rotational conformation of cobalt bis(dicarbollide) and can be used in design of molecular switches. This work was supported by the Russian Science Foundation (16-13-10331).

Keywords: molecular switches, NMR spectroscopy, single crystal X-ray diffraction, transition metal bis(dicarbollide) complexes, quantum chemical calculations

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Authors: Inês Amorim Leitão, Loes van Shaick, António Dinis Ferreira, Violette Geissen

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Plastic pollution is a growing concern worldwide: plastics are commercialized in large quantities and it takes a long time for them to degrade. When in the environment, plastic is fragmented into microplastics (<5mm), which have been found in all environmental compartments at different locations. Microplastics contribute to the environmental pollution in water, air and soil and are linked to human health problems. The progressive increase of population living in cities led to the aggravation of the pollution problem worldwide, especially in urban environments. Urban areas represent a strong source of pollution, through the roads, industrial production, wastewater, landfills, etc. It is expected that pollutants such as microplastics are transported diffusely from the sources through different pathways such as wind and rain. Therefore, it is very complex to quantify, control and treat these pollutants, designated current problematic issues by the European Commission. Green areas are pointed out by experts as natural filters for contaminants in cities, through their capacity of retention by vegetation. These spaces have thus the capacity to control the load of pollutants transported. This study investigates the spatial distribution of microplastics in urban soils of different land uses, their transport through atmospheric deposition, wind erosion, runoff and streams, as well as their deposition in vegetation like grass and tree leaves in urban environment. Coimbra, a medium large city located in the central Portugal, is the case-study. All the soil, sediments, water and vegetation samples were collected in Coimbra and were later analyzed in the Wageningen University & Research laboratory. Microplastics were extracted through the density separation using Sodium Phosphate as solution (~1.4 g cm−3) and filtration methods, visualized under a stereo microscope and identified using the u-FTIR method. Microplastic particles were found in all the different samples. In terms of soils, higher concentrations of microplastics were found in green parks, followed by landfills and industrial places, and the lowest concentrations in forests and pasture land-uses. Atmospheric deposition and streams after rainfall events seems to represent the strongest pathways of microplastics. Tree leaves can retain microplastics on their surfaces. Small leaves such as needle leaves seem to present higher amounts of microplastics per leaf area than bigger leaves. Rainfall episodes seem to reduce the concentration of microplastics on leaves surface, which suggests the wash of microplastics down to lower levels of the tree or to the soil. When in soil, different types of microplastics could be transported to the atmosphere through wind erosion. Grass seems to present high concentrations of microplastics, and the enlargement of the grass cover leads to a reduction of the amount of microplastics in soil, but also of the microplastics moved from the ground to the atmosphere by wind erosion. This study proof that vegetation can help to control the transport and dispersion of microplastics. In order to control the entry and the concentration of microplastics in the environment, especially in cities, it is essential to defining and evaluating nature-based land-use scenarios, considering the role of green urban areas in filtering small particles.

Keywords: microplastics, cities, sources, pathways, vegetation

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Authors: Wen-Yang Hu, Ranli Lu, Mark Maienschein-Cline, Danping Hu, Larisa Nonn, Toshi Shioda, Gail S. Prins

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Background: Genetic mutations are highly associated with increased prostate cancer risk. In addition to whole genome sequencing, somatic mutations can be identified by aligning transcriptome sequences to the human genome. Here we analyzed bulk RNAseq and single cell RNAseq data of human prostate cancer cells and their matched non-cancer cells in benign regions from 4 individual patients. Methods: Sequencing raw reads were aligned to the reference genome hg38 using STAR. Variants were annotated using Annovar with respect to overlap gene annotation information, effect on gene and protein sequence, and SIFT annotation of nonsynonymous variant effect. We determined cancer-specific novel alleles by comparing variant calls in cancer cells to matched benign cells from the same individual by selecting unique alleles that were only detected in the cancer samples. Results: In bulk RNAseq data from 3 patients, the most common variants were the noncoding mutations at UTR3/UTR5, and the major variant types were single-nucleotide polymorphisms (SNP) including frameshift mutations. C>T transversion is the most frequently presented substitution of SNP. A total of 222 genes carrying unique exonic or UTR variants were revealed in cancer cells across 3 patients but not in benign cells. Among them, transcriptome levels of 7 genes (CITED2, YOD1, MCM4, HNRNPA2B1, KIF20B, DPYSL2, NR4A1) were significantly up or down regulated in cancer stem cells. Out of the 222 commonly mutated genes in cancer, 19 have nonsynonymous variants and 11 are damaged genes with variants including SIFT, frameshifts, stop gain/loss, and insertions/deletions (indels). Two damaged genes, activating transcription factor 6 (ATF6) and histone demethylase KDM3A are of particular interest; the former is a survival factor for certain cancer cells while the later positively activates androgen receptor target genes in prostate cancer. Further, single cell RNAseq data of cancer cells and their matched non-cancer benign cells from both primary 2D and 3D tumoroid cultures were analyzed. Similar to the bulk RNAseq data, single cell RNAseq in cancer demonstrated that the exonic mutations are less common than noncoding variants, with SNPs including frameshift mutations the most frequently presented types in cancer. Compared to cancer stem cell enriched-3D tumoroids, 2D cancer cells carried 3-times higher variants, 8-times more coding mutations and 10-times more nonsynonymous SNP. Finally, in both 2D primary and 3D tumoroid cultures, cancer stem cells exhibited fewer coding mutations and noncoding SNP or insertions/deletions than non-stem cancer cells. Summary: Our study demonstrates the usefulness of bulk and single cell RNAseaq data in identifying somatic mutations in prostate cancer, providing an alternative method in screening candidate genes for prostate cancer diagnosis and potential therapeutic targets. Cancer stem cells carry fewer somatic mutations than non-stem cancer cells due to their inherited immortal stand DNA from parental stem cells that explains their long-lived characteristics.

Keywords: prostate cancer, stem cell, genomic mutation, RNAseq

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Authors: Elisa Menardo, Margherita Pasini, Margherita Brondino

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A growing body of empirical research from different areas of inquiry suggests that brief contact with natural environment restore mental resources. The Attention Restoration Theory (ART) is the widespread used and empirical founded theory developed to explain why exposure to nature helps people to recovery cognitive resources. It assumes that contact with nature allows people to free (and then recovery) voluntary attention resources and thus allows them to recover from a cognitive fatigue situation. However, it was suggested that some people could have more cognitive benefit after exposure to urban environment. The objective of this study is to report the results of a meta-analysis on studies (peer-reviewed articles) comparing the restorativeness (the quality to be restorative) perceived in natural environments than those perceived in urban environments. This meta-analysis intended to estimate how much nature environments (forests, parks, boulevards) are perceived to be more restorativeness than urban ones (i.e., the magnitude of the perceived restorativeness’ difference). Moreover, given the methodological difference between study, it studied the potential role of moderator variables as participants (student or other), instrument used (Perceived Restorativeness Scale or other), and procedure (in laboratory or in situ). PsycINFO, PsycARTICLES, Scopus, SpringerLINK, Web of Science online database were used to identify all peer-review articles on restorativeness published to date (k = 167). Reference sections of obtained papers were examined for additional studies. Only 22 independent studies (with a total of 1371 participants) met inclusion criteria (direct exposure to environment, comparison between one outdoor environment with natural element and one without natural element, and restorativeness measured by self-report scale) and were included in meta-analysis. To estimate the average effect size, a random effect model (Restricted Maximum-likelihood estimator) was used because the studies included in the meta-analysis were conducted independently and using different methods in different populations, so no common effect-size was expected. The presence of publication bias was checked using trim and fill approach. Univariate moderator analysis (mixed effect model) were run to determine whether the variable coded moderated the perceived restorativeness difference. Results show that natural environments are perceived to be more restorativeness than urban environments, confirming from an empirical point of view what is now considered a knowledge gained in environmental psychology. The relevant information emerging from this study is the magnitude of the estimated average effect size, which is particularly high (d = 1.99) compared to those that are commonly observed in psychology. Significant heterogeneity between study was found (Q(19) = 503.16, p < 0.001;) and studies’ variability was very high (I2[C.I.] = 96.97% [94.61 - 98.62]). Subsequent univariate moderator analyses were not significant. Methodological difference (participants, instrument, and procedure) did not explain variability between study. Other methodological difference (e.g., research design, environment’s characteristics, light’s condition) could explain this variability between study. In the mine while, studies’ variability could be not due to methodological difference but to individual difference (age, gender, education level) and characteristics (connection to nature, environmental attitude). Furthers moderator analysis are working in progress.

Keywords: meta-analysis, natural environments, perceived restorativeness, urban environments

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Authors: David F. Nettleton, Elodie Bugnicourt, Christian Wasiak, Alejandro Rosales

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In this presentation, preliminary results are given for the modeling and calibration of two different industrial winding MIMO (Multiple Input Multiple Output) processes using machine learning techniques. In contrast to previous approaches which have typically used ‘black-box’ linear statistical methods together with a definition of the mechanical behavior of the process, we use non-linear machine learning algorithms together with a ‘white-box’ rule induction technique to create a supervised model of the fitting error between the expected and real force measures. The final objective is to build a precise model of the winding process in order to control de-tension of the material being wound in the first case, and the friction of the material passing through the die, in the second case. Case 1, Tension Control of a Winding Process. A plastic web is unwound from a first reel, goes over a traction reel and is rewound on a third reel. The objectives are: (i) to train a model to predict the web tension and (ii) calibration to find the input values which result in a given tension. Case 2, Friction Force Control of a Micro-Pullwinding Process. A core+resin passes through a first die, then two winding units wind an outer layer around the core, and a final pass through a second die. The objectives are: (i) to train a model to predict the friction on die2; (ii) calibration to find the input values which result in a given friction on die2. Different machine learning approaches are tested to build models, Kernel Ridge Regression, Support Vector Regression (with a Radial Basis Function Kernel) and MPART (Rule Induction with continuous value as output). As a previous step, the MPART rule induction algorithm was used to build an explicative model of the error (the difference between expected and real friction on die2). The modeling of the error behavior using explicative rules is used to help improve the overall process model. Once the models are built, the inputs are calibrated by generating Gaussian random numbers for each input (taking into account its mean and standard deviation) and comparing the output to a target (desired) output until a closest fit is found. The results of empirical testing show that a high precision is obtained for the trained models and for the calibration process. The learning step is the slowest part of the process (max. 5 minutes for this data), but this can be done offline just once. The calibration step is much faster and in under one minute obtained a precision error of less than 1x10-3 for both outputs. To summarize, in the present work two processes have been modeled and calibrated. A fast processing time and high precision has been achieved, which can be further improved by using heuristics to guide the Gaussian calibration. Error behavior has been modeled to help improve the overall process understanding. This has relevance for the quick optimal set up of many different industrial processes which use a pull-winding type process to manufacture fibre reinforced plastic parts. Acknowledgements to the Openmind project which is funded by Horizon 2020 European Union funding for Research & Innovation, Grant Agreement number 680820

Keywords: data model, machine learning, industrial winding, calibration

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Authors: Mohammad Al-Refai, Majed Wakid

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Introduction: Soil-transmitted diseases (STD) are caused by intestinal worms that are transmitted via various routes into the human body resulting in various clinical manifestations. The intestinal worms causing these infections are known as soil transmitted helminths (STH), including Hook worms, Ascaris lumbricoides (A. lumbricoides), Trichuris trichiura (T. trichiura), and Strongyloides sterocoralis (S. sterocoralis). Objectives: The aim of this study was to investigate the prevalence of STH among newly arrived expatriate labors in Jeddah city, Saudi Arabia, using three different techniques (direct smears, sedimentation concentration, and real-time PCR). Methods: A total of 188 stool specimens were collected and investigated at the parasitology laboratory in the Special Infectious Agents Unit at King Fahd Medical Research Center, King Abdulaziz University in Jeddah, Saudi Arabia. Microscopic examination of wet mount preparations using normal saline and Lugols Iodine was carried out, followed by the formal ether sedimentation method. In addition, real-time PCR was used as a molecular tool to detect several STH and hookworm speciation. Results: Out of 188 stool specimens analyzed, in addition to STH parasite, several other types were detected. 9 samples (4.79%) were positive for Entamoeba coli, 7 samples (3.72%) for T. trichiura, 6 samples (3.19%) for Necator americanus, 4 samples (2.13%) for S. sterocoralis, 4 samples (2.13%) for A. lumbricoides, 4 samples (2.13%) for E. histolytica, 3 samples (1.60%) for Blastocystis hominis, 2 samples (1.06%) for Ancylostoma duodenale, 2 samples (1.06%) for Giardia lamblia, 1 sample (0.53%) for Iodamoeba buetschlii, 1 sample (0.53%) for Hymenolepis nana, 1 sample (0.53%) for Endolimax nana, and 1 sample (0.53%) for Heterophyes heterophyes. Out of the 35 infected cases, 26 revealed single infection, 8 with double infections, and only one triple infection of different STH species and other intestinal parasites. Higher rates of STH infections were detected among housemaids (11 cases) followed by drivers (7 cases) when compared to other occupations. According to educational level, illiterate participants represent the majority of infected workers (12 cases). The majority of workers' positive cases were from the Philippines. In comparison between laboratory techniques, out of the 188 samples screened for STH, real-time PCR was able to detect the DNA in (19/188) samples followed by Ritchie sedimentation technique (18/188), and direct wet smear (7/188). Conclusion: STH infections are a major public health issue to healthcare systems around the world. Communities must be educated on hygiene practices and the severity of such parasites to human health. As far as drivers and housemaids come to close contact with families, including children and elderlies. This may put family members at risk of developing serious side effects related to STH, especially as the majority of workers were illiterate, lacking the basic hygiene knowledge and practices. We recommend the official authority in Jeddah and around the kingdom of Saudi Arabia to revise the standard screening tests for newly arrived workers and enforce regular follow-up inspections to minimize the chances of the spread of STH from expatriate workers to the public.

Keywords: expatriate labors, Jeddah, prevalence, soil transmitted helminths

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Authors: Prajna Paramita Naik, Sujit Kumar Bhutia

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Background: Regardless of the development multimodal treatment strategies, oral squamous cell carcinoma (OSCC) is often associated with a high rate of recurrence, metastasis and chemo- and radio- resistance. The present study inspected the relevance of CD44, ABCB1 and ADAM17 expression as a putative stem cell compartment in oral squamous cell carcinoma (OSCC) and deciphered the role of autophagy in regulating the expression of aforementioned proteins, stemness and chemoresistance. Methods: A retrospective analysis of CD44, ABCB1 and ADAM17 expression with respect to the various clinicopathological factors of sixty OSCC patients were determined via immunohistochemistry. The correlation among CD44, ABCB1 and ADAM17 expression was established. Sphere formation assay, flow cytometry and fluorescence microscopy were conducted to elucidate the stemness and chemoresistance nature of established cisplatin-resistant oral cancer cells (FaDu). The pattern of expression of CD44, ABCB1 and ADAM17 in parental (FaDu-P) and resistant FaDu cells (FaDu-CDDP-R) were investigated through fluorescence microscopy. Western blot analysis of autophagy marker proteins was performed to compare the status of autophagy in parental and resistant FaDu cell. To investigate the role of autophagy in chemoresistance and stemness, sphere formation assay, immunofluorescence and Western blot analysis was performed post transfection with siATG14 and the level of expression of autophagic proteins, mitochondrial protein and stemness-associated proteins were analyzed. The statistical analysis was performed by GraphPad Prism 4.0 software. p-value was defined as follows: not significant (n.s.): p > 0.05;*: p ≤ 0.05; **: p ≤ 0.01; ***: p ≤ 0.001; ****: p ≤ 0.0001 were considered statistically significant. Results: In OSCC, high CD44, ABCB1 and ADAM17 expression were significantly correlated with higher tumor grades and poor differentiation. However, the expression of these proteins was not related to the age and sex of OSCC patients. Moreover, the expression of CD44, ABCB1 and ADAM17 were positively correlated with each other. In vitro and OSCC tissue double labeling experiment data showed that CD44+ cells were highly associated with ABCB1 and ADAM17 expression. Further, FaDu-CDDP-R cells showed higher sphere forming capacity along with increased fraction of the CD44+ population and β-catenin expression FaDu-CDDP-R cells also showed accelerated expression of CD44, ABCB1 and ADAM17. A comparatively higher autophagic flux was observed in FaDu-CDDP-R against FaDu-P cells. The expression of mitochondrial proteins was noticeably reduced in resistant cells as compared to parental cells indicating the occurrence of autophagy-mediated mitochondrial degradation in oral cancer. Moreover, inhibition of autophagy was coupled with the decreased formation of orospheres suggesting autophagy-mediated stemness in oral cancer. Blockade of autophagy was also found to induce the restoration of mitochondrial proteins in FaDu-CDDP-R cells indicating the involvement of mitophagy in chemoresistance. Furthermore, a reduced expression of CD44, ABCB1 and ADAM17 was also observed in ATG14 deficient cells FaDu-P and FaDu-CDDP-R cells. Conclusion: The CD44+ ⁄ABCB1+ ⁄ADAM17+ expression in OSCC might be associated with chemoresistance and a putative CSC compartment. Further, the present study highlights the contribution of mitophagy in chemoresistance and confirms the potential involvement of autophagic regulation in acquisition of stem-like characteristics in OSCC.

Keywords: ABCB1, ADAM17, autophagy, CD44, chemoresistance, mitophagy, OSCC, stemness

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Authors: B. R. Campomanes-Alvarez, P. Quiros, B. Fernandez

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Automatic Speech Recognition (ASR) is a machine-based process of decoding and transcribing oral speech. A typical ASR system receives acoustic input from a speaker or an audio file, analyzes it using algorithms, and produces an output in the form of a text. Some speech recognition systems use Hidden Markov Models (HMMs) to deal with the temporal variability of speech and Gaussian Mixture Models (GMMs) to determine how well each state of each HMM fits a short window of frames of coefficients that represents the acoustic input. Another way to evaluate the fit is to use a feed-forward neural network that takes several frames of coefficients as input and produces posterior probabilities over HMM states as output. Deep neural networks (DNNs) that have many hidden layers and are trained using new methods have been shown to outperform GMMs on a variety of speech recognition systems. Acoustic models for state-of-the-art ASR systems are usually training on massive amounts of data. However, audio files with their corresponding transcriptions can be difficult to obtain, especially in the Spanish language. Hence, in the case of these low-resource scenarios, building an ASR model is considered as a complex task due to the lack of labeled data, resulting in an under-trained system. Semi-supervised learning approaches arise as necessary tasks given the high cost of transcribing audio data. The main goal of this proposal is to develop a procedure based on acoustic semi-supervised learning for Spanish ASR systems by using DNNs. This semi-supervised learning approach consists of: (a) Training a seed ASR model with a DNN using a set of audios and their respective transcriptions. A DNN with a one-hidden-layer network was initialized; increasing the number of hidden layers in training, to a five. A refinement, which consisted of the weight matrix plus bias term and a Stochastic Gradient Descent (SGD) training were also performed. The objective function was the cross-entropy criterion. (b) Decoding/testing a set of unlabeled data with the obtained seed model. (c) Selecting a suitable subset of the validated data to retrain the seed model, thereby improving its performance on the target test set. To choose the most precise transcriptions, three confidence scores or metrics, regarding the lattice concept (based on the graph cost, the acoustic cost and a combination of both), was performed as selection technique. The performance of the ASR system will be calculated by means of the Word Error Rate (WER). The test dataset was renewed in order to extract the new transcriptions added to the training dataset. Some experiments were carried out in order to select the best ASR results. A comparison between a GMM-based model without retraining and the DNN proposed system was also made under the same conditions. Results showed that the semi-supervised ASR-model based on DNNs outperformed the GMM-model, in terms of WER, in all tested cases. The best result obtained an improvement of 6% relative WER. Hence, these promising results suggest that the proposed technique could be suitable for building ASR models in low-resource environments.

Keywords: automatic speech recognition, deep neural networks, machine learning, semi-supervised learning

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Authors: Rosa Nadine Danenberg

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In recent years, bottom-up urban development has started growing as an alternative to conventional top-down planning. In large proportions, citizens and communities initiate small-scale interventions; suddenly seeming to form a trend. As a result, more and more cities are witnessing not only the growth of but also an interest in these initiatives, as they bear the potential to reshape urban spaces. Such alternative city-making efforts cause new dynamics in urban governance, with inevitable consequences for the controlled city planning and its administration. The emergence of enabling relationships between top-down and bottom-up actors signals an increasingly common urban practice. Various case studies show that an enabling relationship is possible, yet, how it can be optimally realized stays rather underexamined. Therefore, the seemingly growing worldwide phenomenon of ‘municipal bottom-up urban development’ necessitates an adequate governance structure. As such, the aim of this research is to contribute knowledge to how municipalities can enable citizen-led urban initiatives from a governance innovation perspective. Empirical case-study research in Stockholm and Istanbul, derived from interviews with founders of four citizen-led urban initiatives and one municipal representative in each city, provided valuable insights to possibilities and constraints for enabling practices. On the one hand, diverging outcomes emphasize the extreme oppositional features of both cases (Stockholm and Istanbul). Firstly, both cities’ characteristics are drastically different. Secondly, the ideologies and motifs for the initiatives to emerge vary widely. Thirdly, the major constraints for citizen-led urban initiatives to relate to the municipality are considerably different. Two types of municipality’s organizational structures produce different underlying mechanisms which demonstrate the constraints. The first municipal organizational structure is steered by bureaucracy (Stockholm). It produces an administrative division that brings up constraints such as the lack of responsibility, transparency and continuity by municipal representatives. The second structure is dominated by municipal politics and governmental hierarchy (Istanbul). It produces informality, lack of transparency and a fragmented civil society. In order to cope with the constraints produced by both types of organizational structures, the initiatives have adjusted their organization to the municipality’s underlying structures. On the other hand, this paper has in fact also come to a rather unifying conclusion. Interestingly, the suggested possibilities for an enabling relationship underline converging new urban governance arrangements. This could imply that for the two varying types of municipality’s organizational structures there is an accurate governance structure. Namely, the combination of a neighborhood council with a municipal guide, with allowance for the initiatives to adopt a politicizing attitude is found as coinciding. Especially its combination appears key to redeem varying constraints. A municipal guide steers the initiatives through bureaucratic struggles, is supported by coproduction methods, while it balances out municipal politics. Next, a neighborhood council, that is politically neutral and run by local citizens, can function as an umbrella for citizen-led urban initiatives. What is crucial is that it should cater for a more entangled relationship between municipalities and initiatives with enhanced involvement of the initiatives in decision-making processes and limited involvement of prevailing constraints pointed out in this research.

Keywords: bottom-up urban development, governance innovation, Istanbul, Stockholm

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Authors: Yi H. Wong, Li L. Chan, Chee O. Leong, Stephen Ambu, Joon W. Mak, Priyadashi S. Sahu

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Background: Acanthamoeba is a free-living opportunistic protist which is ubiquitously distributed in the environment. Virulent Acanthamoeba can cause fatal encephalitis in immunocompromised patients and potential blinding keratitis in immunocompetent contact lens wearers. Approximately 24 species have been identified but only the A. castellanii, A. polyphaga and A. culbertsoni are commonly associated with human infections. Until to date, the precise molecular basis for Acanthamoeba pathogenesis remains unclear. Previous studies reported that Acanthamoeba virulence can be diminished through prolonged axenic culture but revived through serial mouse passages. As no clear explanation on this reversible pathogenesis is established, hereby, we postulate that the epigenetic regulators, DNA-methyltransferases (DNMT) and histone-deacetylases (HDAC), could possibly be involved in granting the virulence plasticity of Acanthamoeba spp. Methods: Four rounds of mouse passages were conducted to revive the virulence potential of the virulence-attenuated Acanthamoeba castellanii strain (ATCC 50492). Briefly, each mouse (n=6/group) was inoculated intraperitoneally with Acanthamoebae cells (2x 105 trophozoites/mouse) and incubated for 2 months. Acanthamoebae cells were isolated from infected mouse organs by culture method and subjected to subsequent mouse passage. In vitro cytopathic, encystment and gelatinolytic assays were conducted to evaluate the virulence characteristics of Acanthamoebae isolates for each passage. PCR primers which targeted on the 2 members (DNMT1 and DNMT2) and 5 members (HDAC1 to 5) of the DNMT and HDAC gene families respectively were custom designed. Quantitative real-time PCR (qPCR) was performed to detect and quantify the relative expression of the two gene families in each Acanthamoeba isolates. Beta-tubulin of A. castellanii (Genbank accession no: XP_004353728) was included as housekeeping gene for data normalisation. PCR mixtures were also analyzed by electrophoresis for amplicons detection. All statistical analyses were performed using the paired one-tailed Student’s t test. Results: Our pathogenicity tests showed that the virulence-reactivated Acanthamoeba had a higher degree of cytopathic effect on vero cells, a better resistance to encystment challenge and a higher gelatinolytic activity which was catalysed by serine protease. qPCR assay showed that DNMT1 expression was significantly higher in the virulence-reactivated compared to the virulence-attenuated Acanthamoeba strain (p ≤ 0.01). The specificity of primers which targeted on DNMT1 was confirmed by sequence analysis of PCR amplicons, which showed a 97% similarity to the published DNA-methyltransferase gene of A. castellanii (GenBank accession no: XM_004332804.1). Out of the five primer pairs which targeted on the HDAC family genes, only HDAC4 expression was significantly difference between the two variant strains. In contrast to DNMT1, HDAC4 expression was much higher in the virulence-attenuated Acanthamoeba strain. Conclusion: Our mouse passages had successfully restored the virulence of the attenuated strain. Our findings suggested that DNA-methyltransferase (DNMT1) and histone deacetylase (HDAC4) expressions are associated with virulence potential of Acanthamoeba spp.

Keywords: acanthamoeba, DNA-methyltransferase, histone deacetylase, virulence-associated proteins

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Authors: Selin Guney, Andres Riquelme

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Among the main purposes of optimal and efficient forecasts of agricultural commodity prices is to guide the firms to advance the economic decision making process such as planning business operations and marketing decisions. Governments are also the beneficiaries and suppliers of agricultural price forecasts. They use this information to establish a proper agricultural policy, and hence, the forecasts affect social welfare and systematic errors in forecasts could lead to a misallocation of scarce resources. Various empirical approaches have been applied to forecast commodity prices that have used different methodologies. Most commonly-used approaches to forecast commodity sectors depend on classical time series models that assume values of the response variables are precise which is quite often not true in reality. Recently, this literature has mostly evolved to a consideration of fuzzy time series models that provide more flexibility in terms of the classical time series models assumptions such as stationarity, and large sample size requirement. Besides, fuzzy modeling approach allows decision making with estimated values under incomplete information or uncertainty. A number of fuzzy time series models have been developed and implemented over the last decades; however, most of them are not appropriate for forecasting repeated and nonconsecutive transitions in the data. The modeling scheme used in this paper eliminates this problem by introducing Markov modeling approach that takes into account both the repeated and nonconsecutive transitions. Also, the determination of length of interval is crucial in terms of the accuracy of forecasts. The problem of determining the length of interval arbitrarily is overcome and a methodology to determine the proper length of interval based on the distribution or mean of the first differences of series to improve forecast accuracy is proposed. The specific purpose of this paper is to propose and investigate the potential of a new forecasting model that integrates methodologies for determining the proper length of interval based on the distribution or mean of the first differences of series and Fuzzy Time Series- Markov Chain model. Moreover, the accuracy of the forecasting performance of proposed integrated model is compared to different univariate time series models and the superiority of proposed method over competing methods in respect of modelling and forecasting on the basis of forecast evaluation criteria is demonstrated. The application is to daily corn and soybean prices observed at three commercially important North Carolina markets; Candor, Cofield and Roaring River for corn and Fayetteville, Cofield and Greenville City for soybeans respectively. One main conclusion from this paper is that using fuzzy logic improves the forecast performance and accuracy; the effectiveness and potential benefits of the proposed model is confirmed with small selection criteria value such MAPE. The paper concludes with a discussion of the implications of integrating fuzzy logic and nonarbitrary determination of length of interval for the reliability and accuracy of price forecasts. The empirical results represent a significant contribution to our understanding of the applicability of fuzzy modeling in commodity price forecasts.

Keywords: commodity, forecast, fuzzy, Markov

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Authors: Luminiţa Duţică, Gheorghe Duţică

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One of the most powerful language innovation in the twentieth century music was the heterophony–hypostasis of the vertical syntax entered into the sphere of interest of many composers, such as George Enescu, Pierre Boulez, Mauricio Kagel, György Ligeti and others. The heterophonic syntax has a history of its growth, which means a succession of different concepts and writing techniques. The trajectory of settling this phenomenon does not necessarily take into account the chronology: there are highly complex primary stages and advanced stages of returning to the simple forms of writing. In folklore, the plurimelodic simultaneities are free or random and originate from the (unintentional) differences/‘deviations’ from the state of unison, through a variety of ornaments, melismas, imitations, elongations and abbreviations, all in a flexible rhythmic and non-periodic/immeasurable framework, proper to the parlando-rubato rhythmics. Within the general framework of the multivocal organization, the heterophonic syntax in elaborate (academic) version has imposed itself relatively late compared with polyphony and homophony. Of course, the explanation is simple, if we consider the causal relationship between the sound vocabulary elements – in this case, the modalism – and the typologies of vertical organization appropriate for it. Therefore, adding up the ‘classic’ pathway of the writing typologies (monody – polyphony – homophony), heterophony - applied equally to the structures of modal, serial or synthesis vocabulary – reclaims necessarily an own macrotemporal form, in the sense of the analogies enshrined by the evolution of the musical styles and languages: polyphony→fugue, homophony→sonata. Concerned about the prospect of edifying a new musical ontology, the composer Ştefan Niculescu experienced – along with the mathematical organization of heterophony according to his own original methods – the possibility of extrapolation of this phenomenon in macrostructural plan, reaching this way to the unique form of ‘synchrony’. Founded on coincidentia oppositorum principle (involving the ‘one-multiple’ binom), the sound architecture imagined by Ştefan Niculescu consists in one (temporal) model / algorithm of articulation of two sound states: 1. monovocality state (principle of identity) and 2. multivocality state (principle of difference). In this context, the heterophony becomes an (auto)generative mechanism, with macrotemporal amplitude, strategy that will be grown by the composer, practically throughout his creation (see the works: Ison I, Ison II, Unisonos I, Unisonos II, Duplum, Triplum, Psalmus, Héterophonies pour Montreux (Homages to Enescu and Bartók etc.). For the present demonstration, we selected one of the most edifying works of Ştefan Niculescu – Simphony II, Opus dacicum – where the form of (heterophony-)synchrony acquires monumental-symphonic features, representing an emblematic case for the complexity level achieved by this type of vertical syntax in the twentieth century music.

Keywords: heterophony, modalism, serialism, synchrony, syntax

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Authors: Xingyu Gao, Qiang Wu

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Patents play a crucial role in protecting innovation and intellectual property. Early prediction of the impact of artificial intelligence (AI) patents helps researchers and companies allocate resources and make better decisions. Understanding the key factors that influence patent impact can assist researchers in gaining a better understanding of the evolution of AI technology and innovation trends. Therefore, identifying highly impactful patents early and providing support for them holds immeasurable value in accelerating technological progress, reducing research and development costs, and mitigating market positioning risks. Despite the extensive research on AI patents, accurately predicting their early impact remains a challenge. Traditional methods often consider only single factors or simple combinations, failing to comprehensively and accurately reflect the actual impact of patents. This paper utilized the artificial intelligence patent database from the United States Patent and Trademark Office and the Len.org patent retrieval platform to obtain specific information on 35,708 AI patents. Using six machine learning models, namely Multiple Linear Regression, Random Forest Regression, XGBoost Regression, LightGBM Regression, Support Vector Machine Regression, and K-Nearest Neighbors Regression, and using early indicators of patents as features, the paper comprehensively predicted the impact of patents from three aspects: technical, social, and economic. These aspects include the technical leadership of patents, the number of citations they receive, and their shared value. The SHAP (Shapley Additive exPlanations) metric was used to explain the predictions of the best model, quantifying the contribution of each feature to the model's predictions. The experimental results on the AI patent dataset indicate that, for all three target variables, LightGBM regression shows the best predictive performance. Specifically, patent novelty has the greatest impact on predicting the technical impact of patents and has a positive effect. Additionally, the number of owners, the number of backward citations, and the number of independent claims are all crucial and have a positive influence on predicting technical impact. In predicting the social impact of patents, the number of applicants is considered the most critical input variable, but it has a negative impact on social impact. At the same time, the number of independent claims, the number of owners, and the number of backward citations are also important predictive factors, and they have a positive effect on social impact. For predicting the economic impact of patents, the number of independent claims is considered the most important factor and has a positive impact on economic impact. The number of owners, the number of sibling countries or regions, and the size of the extended patent family also have a positive influence on economic impact. The study primarily relies on data from the United States Patent and Trademark Office for artificial intelligence patents. Future research could consider more comprehensive data sources, including artificial intelligence patent data, from a global perspective. While the study takes into account various factors, there may still be other important features not considered. In the future, factors such as patent implementation and market applications may be considered as they could have an impact on the influence of patents.

Keywords: patent influence, interpretable machine learning, predictive models, SHAP

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Authors: Miria Gambardella

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The influence of solidarity demonstrations towards the Zapatista National Liberation Army has been constantly present over the years, both locally and internationally, guaranteeing visibility to the cause, shaping the movement’s choices, and influencing its hopes of impact worldwide. Most of the coffee produced by the autonomous cooperatives from Chiapas is exported, therefore making coffee trade the main income from international solidarity networks. The question arises about the implications of the relations established between the communities in resistance in Southeastern Mexico and international solidarity movements, specifically on the strategies adopted to conciliate army's demands for autonomy and economic asymmetries between Zapatista cooperatives producing coffee and European collectives who hold purchasing power. In order to deepen the inquiry on those topics, a year-long multi-site investigation was carried out. The first six months of fieldwork were based in Barcelona, where Zapatista coffee was first traded in Spain and where one of the historical and most important European solidarity groups can be found. The last six months of fieldwork were carried out directly in Chiapas, in contact with coffee producers, Zapatista political authorities, international activists as well as vendors, and the rest of the network implicated in coffee production, roasting, and sale. The investigation was based on qualitative research methods, including participatory observation, focus groups, and semi-structured interviews. The analysis did not only focus on retracing the steps of the market chain as if it could be considered a linear and unilateral process, but it rather aimed at exploring actors’ reciprocal perceptions, roles, and dynamics of power. Demonstrations of solidarity and the money circulation they imply aim at changing the system in place and building alternatives, among other things, on the economic level. This work analyzes the formulation of discourse and the organization of solidarity activities that aim at building opportunities for action within a highly politicized economic sphere to which access must be regularly legitimized. The meaning conveyed by coffee is constructed on a symbolic level by the attribution of moral criteria to transactions. The latter participate in the construction of imaginaries that circulate through solidarity movements with the Zapatista rebellion. Commercial exchanges linked to solidarity networks turned out to represent much more than monetary transactions. The social, cultural, and political spheres are invested by ethics, which penetrates all aspects of militant action. It is at this level that the boundaries of different collective actors connect, contaminating each other: merely following the money flow would have been limiting in order to account for a reality within which imaginary is one of the main currencies. The notions of “trust”, “dignity” and “reciprocity” are repeatedly mobilized to negotiate discontinuous and multidirectional flows in the attempt to balance and justify commercial relations in a politicized context that characterizes its own identity through demonizing “market economy” and its dehumanizing powers.

Keywords: coffee trade, economic anthropology, international cooperation, Zapatista National Liberation Army

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Authors: Rohan M. Dalal, Elena Pirondini, Shanu Somvanshi

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Introduction: The current state of reproductive health outcomes in lower-income countries is poor, with inadequate knowledge and culture among adolescent boys. Moreover, boys have traditionally not been a priority target. To explore the opportunity to educate adolescent boys in the developing world regarding accurate reproductive health information, the purpose of this study is to investigate how adolescent boys in the developing world engage and use technology, utilizing cell phones. This electronic survey and video interview study were conducted to determine the feasibility of a mobile phone platform for an educational video game specifically designed for boys that will improve health knowledge, influence behavior, and change health outcomes, namely teen pregnancies. Methods: With the assistance of Plan India, a subsidiary of Plan International, informed consent was obtained from parents of adolescent males who participated in an electronic survey and video interviews via Microsoft Teams. An electronic survey was created with 27 questions, including topics of mobile phone usage, gaming preferences, and sexual and reproductive health, with a sample size of 181 adolescents, ages 11-25, near New Delhi, India. The interview questions were written to explore more in-depth topics after the completion of the electronic survey. Eight boys, aged 15, were interviewed for 40 minutes about gaming and usage of mobile phones as well as sexual and reproductive health. Data/Results. 154 boys and 27 girls completed the survey. They rated their English fluency as relatively high. 97% of boys (149/154) had access to mobile phones. The majority of phones were smartphones (97%, 143/148). 48% (71/149) of boys borrowed cell phones. The most popular phone platform was Samsung (22%, 33/148). 36% (54/148) of adolescent males looked at their phones 1-10 times per day for 1-2 hours. 55% (81/149) of the boys had parental restrictions. 51% (76/148) had 32 GB of storage on their phone. 78% (117/150) of the boys had wifi access. 80% (120/150) of respondents reported ease in downloading apps. 97% (145/150) of male adolescents had social media, including WhatsApp, Facebook, and YouTube. 58% (87/150) played video games. Favorite video games included Free Fire, PubG, and other shooting games. In the video interviews, the boys revealed what made games fun and engaging, including customized avatars, progression to higher levels, realistic interactive platforms, shooting/guns, the ability to perform multiple actions, and a variety of worlds/settings/adventures. Ideas to improve engagement in sexual and reproductive health classes included open discussions in the community, enhanced access to information, and posting on social media. Conclusion: This study involving an electronic survey and video interviews provides an initial foray into understanding mobile phone usage among adolescent males and understanding sexual and reproductive health education in New Delhi, India. The data gathered from this study support using mobile phone platforms, and this will be used to create a serious video game to educate adolescent males about sexual and reproductive health in an attempt to lower the rate of unwanted pregnancies in the world.

Keywords: adolescent males, India, mobile phone, sexual and reproductive health

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Authors: Samuel McLennan, Tane Moleta, Andre Brown, Marc Aurel Schnabel

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The development of Ecclesiastical buildings within New Zealand has produced some unique design characteristics that take influence from both international styles and local building methods. What this research looks at is how procedural modelling can be used to define such common characteristics and understand how they are shared and developed within different examples of a similar architectural style. This will be achieved through the creation of procedural digital reconstructions of the various timber Gothic Churches built during the 19th century in the city of Wellington, New Zealand. ‘Procedural modelling’ is a digital modelling technique that has been growing in popularity, particularly within the game and film industry, as well as other fields such as industrial design and architecture. Such a design method entails the creation of a parametric ‘ruleset’ that can be easily adjusted to produce many variations of geometry, rather than a single geometry as is typically found in traditional CAD software. Key precedents within this area of digital heritage includes work by Haegler, Müller, and Gool, Nicholas Webb and Andre Brown, and most notably Mark Burry. What these precedents all share is how the forms of the reconstructed architecture have been generated using computational rules and an understanding of the architects’ geometric reasoning. This is also true within this research as Gothic architecture makes use of only a select range of forms (such as the pointed arch) that can be accurately replicated using the same standard geometric techniques originally used by the architect. The methodology of this research involves firstly establishing a sample group of similar buildings, documenting the existing samples, researching any lost samples to find evidence such as architectural plans, photos, and written descriptions, and then culminating all the findings into a single 3D procedural asset within the software ‘Houdini’. The end result will be an adjustable digital model that contains all the architectural components of the sample group, such as the various naves, buttresses, and windows. These components can then be selected and arranged to create visualisations of the sample group. Because timber gothic churches in New Zealand share many details between designs, the created collection of architectural components can also be used to approximate similar designs not included in the sample group, such as designs found beyond the Wellington Region. This creates an initial library of architectural components that can be further expanded on to encapsulate as wide of a sample size as desired. Such a methodology greatly improves upon the efficiency and adjustability of digital modelling compared to current practices found in digital heritage reconstruction. It also gives greater accuracy to speculative design, as a lack of evidence for lost structures can be approximated using components from still existing or better-documented examples. This research will also bring attention to the cultural significance these types of buildings have within the local area, addressing the public’s general unawareness of architectural history that is identified in the Wellington based research ‘Moving Images in Digital Heritage’ by Serdar Aydin et al.

Keywords: digital forensics, digital heritage, gothic architecture, Houdini, procedural modelling

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Authors: Rajkumar Ghosh

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Water scarcity is a pressing issue in urban areas, even in smart cities where efficient resource management is a priority. This scarcity is mainly caused by factors such as lifestyle changes, excessive groundwater extraction, over-usage of water, rapid urbanization, and uncontrolled population growth. In the specific case of Gomti Nagar, Lucknow, Uttar Pradesh, India, the depletion of groundwater resources is particularly severe, leading to a water imbalance and posing a significant challenge for the region's sustainable development. The aim of this study is to address the water shortage in the Gomti Nagar region by focusing on the implementation of artificial groundwater recharge methods. Specifically, the research aims to investigate the effectiveness of rainwater collection through rooftop rainwater harvesting systems (RTRWHs) as a sustainable approach to reduce aquifer depletion and bridge the gap between groundwater recharge and extraction. The research methodology for this study involves the utilization of RTRWHs as the main method for collecting rainwater. This approach is considered effective in managing and conserving water resources in a sustainable manner. The focus is on implementing RTRWHs in residential and commercial buildings to maximize the collection of rainwater and its subsequent utilization for various purposes in the Gomti Nagar region. The study reveals that the installation of RTRWHs in the Gomti Nagar region has a positive impact on addressing the water scarcity issue. Currently, RTRWHs cover only a small percentage (0.04%) of the total rainfall collected in the region. However, when RTRWHs are installed in all buildings, their influence on increasing water availability and reducing aquifer depletion will be significantly greater. The study also highlights the significant water imbalance of 24519 ML/yr in the region, emphasizing the urgent need for sustainable water management practices. This research contributes to the theoretical understanding of sustainable water management systems in smart cities. By highlighting the effectiveness of RTRWHs in reducing aquifer depletion, it emphasizes the importance of implementing such systems in urban areas. The findings of this study can serve as a basis for policymakers, urban planners, and developers to prioritize and incentivize the installation of RTRWHs as a potential solution to the water shortage crisis. The data for this study were collected through various sources such as government reports, surveys, and existing groundwater abstraction patterns. The collected data were then analysed to assess the current water situation, groundwater depletion rate, and the potential impact of implementing RTRWHs. Statistical analysis and modelling techniques were employed to quantify the water imbalance and evaluate the effectiveness of RTRWHs. The findings of this study demonstrate that the implementation of RTRWHs can effectively mitigate the water scarcity crisis in Gomti Nagar. By reducing aquifer depletion and bridging the gap between groundwater recharge and extraction, RTRWHs offer a sustainable solution to the region's water scarcity challenges. The study highlights the need for widespread adoption of RTRWHs in all buildings and emphasizes the importance of integrating such systems into the urban planning and development process. By doing so, smart cities like Gomti Nagar can achieve efficient water management, ensuring a better future with improved water availability for its residents.

Keywords: rooftop rainwater harvesting, rainwater, water management, aquifer

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Authors: Naghmeh M. Bandari, Javad Dargahi, Muthukumaran Packirisamy

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Robot-assisted minimally invasive surgery (RMIS) has been widely performed around the world during the last two decades. RMIS demonstrates significant advantages over conventional surgery, e.g., improving the accuracy and dexterity of a surgeon, providing 3D vision, motion scaling, hand-eye coordination, decreasing tremor, and reducing x-ray exposure for surgeons. Despite benefits, surgeons cannot touch the surgical site and perceive tactile information. This happens due to the remote control of robots. The literature survey identified the lack of force feedback as the riskiest limitation in the existing technology. Without the perception of tool-tissue contact force, the surgeon might apply an excessive force causing tissue laceration or insufficient force causing tissue slippage. The primary use of force sensors has been to measure the tool-tissue interaction force in real-time in-situ. Design of a tactile sensor is subjected to a set of design requirements, e.g., biocompatibility, electrical-passivity, MRI-compatibility, miniaturization, ability to measure static and dynamic force. In this study, a planar optical fiber-based sensor was proposed to mount at the surgical grasper. It was developed based on the light intensity modulation principle. The deflectable part of the sensor was a beam modeled as a cantilever Euler-Bernoulli beam on rigid substrates. A semi-cylindrical indenter was attached to the bottom surface the beam at the mid-span. An optical fiber was secured at both ends on the same rigid substrates. The indenter was in contact with the fiber. External force on the sensor caused deflection in the beam and optical fiber simultaneously. The micro-bending of the optical fiber would consequently result in light power loss. The sensor was simulated and studied using finite element methods. A laser light beam with 800nm wavelength and 5mW power was used as the input to the optical fiber. The output power was measured using a photodetector. The voltage from photodetector was calibrated to the external force for a chirp input (0.1-5Hz). The range, resolution, and hysteresis of the sensor were studied under monotonic and harmonic external forces of 0-2.0N with 0 and 5Hz, respectively. The results confirmed the validity of proposed sensing principle. Also, the sensor demonstrated an acceptable linearity (R2 > 0.9). A minimum external force was observed below which no power loss was detectable. It is postulated that this phenomenon is attributed to the critical angle of the optical fiber to observe total internal reflection. The experimental results were of negligible hysteresis (R2 > 0.9) and in fair agreement with the simulations. In conclusion, the suggested planar sensor is assessed to be a cost-effective solution, feasible, and easy to use the sensor for being miniaturized and integrated at the tip of robotic graspers. Geometrical and optical factors affecting the minimum sensible force and the working range of the sensor should be studied and optimized. This design is intrinsically scalable and meets all the design requirements. Therefore, it has a significant potential of industrialization and mass production.

Keywords: force sensor, minimally invasive surgery, optical sensor, robotic surgery, tactile sensor

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Authors: Nalika S. Rajapaksha, James Airton, Amina Aboobakar, Nick Chappell, Andy Dyer

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Nutrient pollution and their impact on water quality is a key concern in England. Many water quality issues originate from multiple sources of pollution spread across the catchment. The river water quality in England has improved since 1990s and wastewater effluent discharges into rivers now contain less phosphorus than in the past. However, excess phosphorus is still recognised as the prevailing issue for rivers failing Water Framework Directive (WFD) good ecological status. To achieve WFD Phosphorus objectives, Wastewater Treatment Works (WwTW) permit limits are becoming increasingly stringent. Nevertheless, in some rural catchments, the apportionment of Phosphorus pollution can be greater from agricultural runoff and other sources such as septic tanks. Therefore, the challenge of meeting the requirements of watercourses to deliver WFD objectives often goes beyond water company activities, providing significant opportunities to co-deliver activities in wider catchments to reduce nutrient load at source. The aim of this study was to apply the United Utilities' Catchment Systems Thinking (CaST) strategy and pilot an innovative permitting approach - Catchment Nutrient Balancing (CNB) in a rural catchment in Cumbria (the River Petteril) in collaboration with the regulator and others to achieve WFD objectives and multiple benefits. The study area is mainly agricultural land, predominantly livestock farms. The local ecology is impacted by significant nutrient inputs which require intervention to meet WFD obligations. There are a range of Phosphorus inputs into the river, including discharges from wastewater assets but also significantly from agricultural contributions. Solely focusing on the WwTW discharges would not have resolved the problem hence in order to address this issue effectively, a CNB trial was initiated at a small WwTW, targeting the removal of a total of 150kg of Phosphorus load, of which 13kg were to be reduced through the use of catchment interventions. Various catchment interventions were implemented across selected farms in the upstream of the catchment and also an innovative polonite reactive filter media was implemented at the WwTW as an alternative to traditional Phosphorus treatment methods. During the 3 years of this trial, the impact of the interventions in the catchment and the treatment works were monitored. In 2020 and 2022, it respectively achieved a 69% and 63% reduction in the phosphorus level in the catchment against the initial reduction target of 9%. Phosphorus treatment at the WwTW had a significant impact on overall load reduction. The wider catchment impact, however, was seven times greater than the initial target when wider catchment interventions were also established. While it is unlikely that all the Phosphorus load reduction was delivered exclusively from the interventions implemented though this project, this trial evidenced the enhanced benefits that can be achieved with an integrated approach, that engages all sources of pollution within the catchment - rather than focusing on a one-size-fits-all solution. Primarily, the CNB approach and the act of collaboratively engaging others, particularly the agriculture sector is likely to yield improved farm and land management performance and better compliance, which can lead to improved river quality as well as wider benefits.

Keywords: agriculture, catchment nutrient balancing, phosphorus pollution, water quality, wastewater

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Authors: Chen Jiang, Eric Jordan, Maurice Gell, Balakrishnan Nair

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Nuclear fusion, one of the most promising options for reliably generating large amounts of carbon-free energy in the future, has seen a plethora of ground-breaking technological advances in recent years. An efficient and durable “breeding blanket”, needed to ensure a reactor’s self-sufficiency by maintaining the optimal coolant temperature as well as by minimizing radiation dosage behind the blanket, still remains a technological challenge for the various reactor designs for commercial fusion power plants. A relatively new dual-coolant lead-lithium (DCLL) breeder design has exhibited great potential for high-temperature (>700oC), high-thermal-efficiency (>40%) fusion reactor operation. However, the structural material, namely reduced activation ferritic-martensitic (RAFM) steel, is not chemically stable in contact with molten Pb-17%Li coolant. Thus, to utilize this new promising reactor design, the demand for effective corrosion-resistant coatings on RAFM steels represents a pressing need. Solution Spray Technologies LLC (SST) is developing a double-layer ceramic coating design to address the corrosion protection of RAFM steels, using a novel solution and solution/suspension plasma spray technology through a US Department of Energy-funded project. Plasma spray is a coating deposition method widely used in many energy applications. Novel derivatives of the conventional powder plasma spray process, known as the solution-precursor and solution/suspension-hybrid plasma spray process, are powerful methods to fabricate thin, dense ceramic coatings with complex compositions necessary for the corrosion protection in DCLL breeders. These processes can be used to produce ultra-fine molten splats and to allow fine adjustment of coating chemistry. Thin, dense ceramic coatings with chosen chemistry for superior chemical stability in molten Pb-Li, low activation properties, and good radiation tolerance, is ideal for corrosion-protection of RAFM steels. A key challenge is to accommodate its CTE mismatch with the RAFM substrate through the selection and incorporation of appropriate bond layers, thus allowing for enhanced coating durability and robustness. Systematic process optimization is being used to define the optimal plasma spray conditions for both the topcoat and bond-layer, and X-ray diffraction and SEM-EDS are applied to successfully validate the chemistry and phase composition of the coatings. The plasma-sprayed double-layer corrosion resistant coatings were also deposited onto simulated RAFM steel substrates, which are being tested separately under thermal cycling, high-temperature moist air oxidation as well as molten Pb-Li capsule corrosion conditions. Results from this testing on coated samples, and comparisons with bare RAFM reference samples will be presented and conclusions will be presented assessing the viability of the new ceramic coatings to be viable corrosion prevention systems for DCLL breeders in commercial nuclear fusion reactors.

Keywords: breeding blanket, corrosion protection, coating, plasma spray

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Authors: Pedro A. Marques, Francisco Monteiro, Alessandra Zumbo, Alessia Simonini, Miguel A. Mendez

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Cryogenic fuels such as Liquid Hydrogen (LH₂) must be transported and stored at extremely low temperatures. Without expensive active cooling solutions, preventing fuel boil-off over time is impossible. Hence, one must resort to venting systems at the cost of significant energy and fuel mass loss. These losses increase significantly in propellant tanks installed on vehicles, as the presence of external accelerations induces sloshing. Sloshing increases heat and mass transfer rates and leads to significant pressure oscillations, which might further trigger propellant venting. To make LH₂ economically viable, it is essential to minimize these factors by using advanced control techniques. However, these require accurate modelling and a full understanding of the tank's thermodynamics. The present research aims to implement a simple thermodynamic model capable of predicting the state of a cryogenic fuel tank under different operating conditions (i.e., filling, pressurization, fuel extraction, long-term storage, and sloshing). Since this model relies on a set of closure parameters to drive the system's transient response, it must be calibrated using experimental or numerical data. This work focuses on the former approach, wherein the model is calibrated through an experimental campaign carried out on a reduced-scale model of a cryogenic tank. The thermodynamic model of the system is composed of three control volumes: the ullage, the liquid, and the insulating walls. Under this lumped formulation, the governing equations are derived from energy and mass balances in each region, with mass-averaged properties assigned to each of them. The gas-liquid interface is treated as an infinitesimally thin region across which both phases can exchange mass and heat. This results in a coupled system of ordinary differential equations, which must be closed with heat and mass transfer coefficients between each control volume. These parameters are linked to the system evolution via empirical relations derived from different operating regimes of the tank. The derivation of these relations is carried out using an inverse method to find the optimal relations that allow the model to reproduce the available data. This approach extends classic system identification methods beyond linear dynamical systems via a nonlinear optimization step. Thanks to the data-driven assimilation of the closure problem, the resulting model accurately predicts the evolution of the tank's thermodynamics at a negligible computational cost. The lumped model can thus be easily integrated with other submodels to perform complete system simulations in real time. Moreover, by setting the model in a dimensionless form, a scaling analysis allowed us to relate the tested configurations to a representative full-size tank for naval applications. It was thus possible to compare the relative importance of different transport phenomena between the laboratory model and the full-size prototype among the different operating regimes.

Keywords: destratification, hydrogen, modeling, pressure-drop, pressurization, sloshing, thermodynamics

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Authors: Paola Montenegro, Maria de los Angeles Balaguera Villa

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In February 2022 Colombia achieved a historic milestone in ensuring universal access to abortion rights with ruling C-055 of 2022 decriminalising abortion up to 24 weeks of gestation. In the context of this triumph and the expansion of telemedicine services in the wake of the COVID-19 pandemic, this research studied the acceptability of self-care abortion in young people (13 - 28 years) through a telemedicine service and also explored the primary needs that should be the focus of such care. The results shine light on a more comprehensive understanding of opportunities and challenges of teleabortion practices in a context that combines overall higher access to technology and low access to reliable information of safe abortion, stigma, and scarcity especially felt by transnational migrants, racialised people, trans men and non-binary people. Through a mixed methods approach, this study collected 5.736 responses to a virtual survey disseminated nationwide in Colombia and 47 in-person interviews (24 of them with people who were assigned female at birth and 21 with local key stakeholders in the abortion ecosystem). Quantitative data was analyzed using Stata SE Version 16.0 and qualitative analysis was completed through NVivo using thematic analysis. Key findings of the research suggest that self-care abortion is practice with growing acceptability among young people, but important adjustments must be made to meet quality of care expectations of users. Elements like quick responses from providers, lower costs, and accessible information were defined by users as decisive factors to choose over the abortion service provider. In general, the narratives in participants about quality care were centred on the promotion of autonomy and the provision of accompaniment and care practices, also perceived as transformative and currently absent of most health care services. The most staggering findings from the investigation are related to current barriers faced by young people in abortion contexts even when the legal barriers have: high rates of scepticism and distrust associated with pitfalls of telehealth and structural challenges associated with lacking communications infrastructure, among a few of them. Other important barriers to safe self-care abortion identified by participants surfaced like lack of privacy and confidentiality (especially in rural areas of the country), difficulties accessing reliable information, high costs of procedures and expenses related to travel costs or having to cease economic activities, waiting times, and stigma are among the primary barriers to abortion identified by participants. Especially in a scenario marked by unprecedented social, political and economic disruptions due to the COVID-19 pandemic, the commitment to design better care services that can be adapted to the identities, experiences, social contexts and possibilities of the user population is more necessary than ever. In this sense, the possibility of expanding access to services through telemedicine brings us closer to the opportunity to rethink the role of health care models in transforming the role of individuals and communities to make autonomous, safe and informed decisions about their own health and well-being.

Keywords: contraception, family planning, premarital fertility, unplanned pregnancy

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Authors: Varun Kumar, Chandra Shakher

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Micro-optical components such as microlenses and microlens array have numerous engineering and industrial applications for collimation of laser diodes, imaging devices for sensor system (CCD/CMOS, document copier machines etc.), for making beam homogeneous for high power lasers, a critical component in Shack-Hartmann sensor, fiber optic coupling and optical switching in communication technology. Also micro-optical components have become an alternative for applications where miniaturization, reduction of alignment and packaging cost are necessary. The compliance with high-quality standards in the manufacturing of micro-optical components is a precondition to be compatible on worldwide markets. Therefore, high demands are put on quality assurance. For quality assurance of these lenses, an economical measurement technique is needed. For cost and time reason, technique should be fast, simple (for production reason), and robust with high resolution. The technique should provide non contact, non-invasive and full field information about the shape of micro- optical component under test. The interferometric techniques are noncontact type and non invasive and provide full field information about the shape of the optical components. The conventional interferometric technique such as holographic interferometry or Mach-Zehnder interferometry is available for characterization of micro-lenses. However, these techniques need more experimental efforts and are also time consuming. Digital holography (DH) overcomes the above described problems. Digital holographic microscopy (DHM) allows one to extract both the amplitude and phase information of a wavefront transmitted through the transparent object (microlens or microlens array) from a single recorded digital hologram by using numerical methods. Also one can reconstruct the complex object wavefront at different depths due to numerical reconstruction. Digital holography provides axial resolution in nanometer range while lateral resolution is limited by diffraction and the size of the sensor. In this paper, Mach-Zehnder based digital holographic interferometric microscope (DHIM) system is used for the testing of transparent microlenses. The advantage of using the DHIM is that the distortions due to aberrations in the optical system are avoided by the interferometric comparison of reconstructed phase with and without the object (microlens array). In the experiment, first a digital hologram is recorded in the absence of sample (microlens array) as a reference hologram. Second hologram is recorded in the presence of microlens array. The presence of transparent microlens array will induce a phase change in the transmitted laser light. Complex amplitude of object wavefront in presence and absence of microlens array is reconstructed by using Fresnel reconstruction method. From the reconstructed complex amplitude, one can evaluate the phase of object wave in presence and absence of microlens array. Phase difference between the two states of object wave will provide the information about the optical path length change due to the shape of the microlens. By the knowledge of the value of the refractive index of microlens array material and air, the surface profile of microlens array is evaluated. The Sag of microlens and radius of curvature of microlens are evaluated and reported. The sag of microlens agrees well within the experimental limit as provided in the specification by the manufacturer.

Keywords: micro-optics, microlens array, phase map, digital holographic interferometric microscopy

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Authors: Sree Bash Chandra Debnath, Didier Tonneau, Carole Fauquet, Agnes Tallet, Julien Darreon

Abstract:

Purpose: Inorganic scintillating dosimetry is the most recent promising technique to solve several dosimetric issues and provide quality assurance in radiation therapy. Despite several advantages, the major issue of using scintillating detectors is the Cerenkov effect, typically induced in the visible emission range. In this context, the purpose of this research work is to evaluate the performance of a novel infrared inorganic scintillator detector (IR-ISD) in the radiation therapy treatment to ensure Cerenkov free signal and the best matches between the delivered and prescribed doses during treatment. Methods: A simple and small-scale infrared inorganic scintillating detector of 100 µm diameter with a sensitive scintillating volume of 2x10-6 mm3 was developed. A prototype of the dose verification system has been introduced based on PTIR1470/F (provided by Phosphor Technology®) material used in the proposed novel IR-ISD. The detector was tested on an Elekta LINAC system tuned at 6 MV/15MV and a brachytherapy source (Ir-192) used in the patient treatment protocol. The associated dose rate was measured in count rate (photons/s) using a highly sensitive photon counter (sensitivity ~20ph/s). Overall measurements were performed in IBATM water tank phantoms by following international Technical Reports series recommendations (TRS 381) for radiotherapy and TG43U1 recommendations for brachytherapy. The performance of the detector was tested through several dosimetric parameters such as PDD, beam profiling, Cerenkov measurement, dose linearity, dose rate linearity repeatability, and scintillator stability. Finally, a comparative study is also shown using a reference microdiamond dosimeter, Monte-Carlo (MC) simulation, and data from recent literature. Results: This study is highlighting the complete removal of the Cerenkov effect especially for small field radiation beam characterization. The detector provides an entire linear response with the dose in the 4cGy to 800 cGy range, independently of the field size selected from 5 x 5 cm² down to 0.5 x 0.5 cm². A perfect repeatability (0.2 % variation from average) with day-to-day reproducibility (0.3% variation) was observed. Measurements demonstrated that ISD has superlinear behavior with dose rate (R2=1) varying from 50 cGy/s to 1000 cGy/s. PDD profiles obtained in water present identical behavior with a build-up maximum depth dose at 15 mm for different small fields irradiation. A low dimension of 0.5 x 0.5 cm² field profiles have been characterized, and the field cross profile presents a Gaussian-like shape. The standard deviation (1σ) of the scintillating signal remains within 0.02% while having a very low convolution effect, thanks to lower sensitive volume. Finally, during brachytherapy, a comparison with MC simulations shows that considering energy dependency, measurement agrees within 0.8% till 0.2 cm source to detector distance. Conclusion: The proposed scintillating detector in this study shows no- Cerenkov radiation and efficient performance for several radiation therapy measurement parameters. Therefore, it is anticipated that the IR-ISD system can be promoted to validate with direct clinical investigations, such as appropriate dose verification and quality control in the Treatment Planning System (TPS).

Keywords: IR-Scintillating detector, dose measurement, micro-scintillators, Cerenkov effect

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Yogesh Kumar Singh, T. S. Murugesh Prabhu, Upasana Dutta, Girishchandra Yendargaye, Rahul Yadav, Rohini Gopinath Kale, Binay Kumar, Manoj Khare

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The Indian subcontinent is severely affected by floods that cause intense irreversible devastation to crops and livelihoods. With increased incidences of floods and their related catastrophes, an Early Warning System for Flood Prediction and an efficient Flood Management System for the river basins of India is a must. Accurately modeled hydrological conditions and a web-based early warning system may significantly reduce economic losses incurred due to floods and enable end users to issue advisories with better lead time. This study describes the design and development of an EWS-FP using advanced computational tools/methods, viz. High-Performance Computing (HPC), Remote Sensing, GIS technologies, and open-source tools for the Mahanadi River Basin of India. The flood prediction is based on a robust 2D hydrodynamic model, which solves shallow water equations using the finite volume method. Considering the complexity of the hydrological modeling and the size of the basins in India, it is always a tug of war between better forecast lead time and optimal resolution at which the simulations are to be run. High-performance computing technology provides a good computational means to overcome this issue for the construction of national-level or basin-level flash flood warning systems having a high resolution at local-level warning analysis with a better lead time. High-performance computers with capacities at the order of teraflops and petaflops prove useful while running simulations on such big areas at optimum resolutions. In this study, a free and open-source, HPC-based 2-D hydrodynamic model, with the capability to simulate rainfall run-off, river routing, and tidal forcing, is used. The model was tested for a part of the Mahanadi River Basin (Mahanadi Delta) with actual and predicted discharge, rainfall, and tide data. The simulation time was reduced from 8 hrs to 3 hrs by increasing CPU nodes from 45 to 135, which shows good scalability and performance enhancement. The simulated flood inundation spread and stage were compared with SAR data and CWC Observed Gauge data, respectively. The system shows good accuracy and better lead time suitable for flood forecasting in near-real-time. To disseminate warning to the end user, a network-enabled solution is developed using open-source software. The system has query-based flood damage assessment modules with outputs in the form of spatial maps and statistical databases. System effectively facilitates the management of post-disaster activities caused due to floods, like displaying spatial maps of the area affected, inundated roads, etc., and maintains a steady flow of information at all levels with different access rights depending upon the criticality of the information. It is designed to facilitate users in managing information related to flooding during critical flood seasons and analyzing the extent of the damage.

Keywords: flood, modeling, HPC, FOSS

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Authors: D. Heinemann, S. Schramm, S. Knabner, D. Baumgarten

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Purpose: Applying solder paste to printed circuit boards (PCB) with stencils has been the method of choice over the past years. A new method uses a jet printer to deposit tiny droplets of solder paste through an ejector mechanism onto the board. This allows for more flexible PCB layouts with smaller components. Due to the viscosity of the solder paste, air blisters can be trapped in the cartridge. This can lead to missing solder joints or deviations in the applied solder volume. Therefore, a built-in and real-time inspection of the printing process is needed to minimize uncertainties and increase the efficiency of the process by immediate correction. The objective of the current study is the design of an optimal imaging system and the development of an automatic algorithm for the detection of applied solder joints from optical from the captured images. Methods: In a first approach, a camera module connected to a microcomputer and LED strips are employed to capture images of the printed circuit board under four different illuminations (white, red, green and blue). Subsequently, an improved system including a ring light, an objective lens, and a monochromatic camera was set up to acquire higher quality images. The obtained images can be divided into three main components: the PCB itself (i.e., the background), the reflections induced by unsoldered positions or screw holes and the solder joints. Non-uniform illumination is corrected by estimating the background using a morphological opening and subtraction from the input image. Image sharpening is applied in order to prevent error pixels in the subsequent segmentation. The intensity thresholds which divide the main components are obtained from the multimodal histogram using three probability density functions. Determining the intersections delivers proper thresholds for the segmentation. Remaining edge gradients produces small error areas which are removed by another morphological opening. For quantitative analysis of the segmentation results, the dice coefficient is used. Results: The obtained PCB images show a significant gradient in all RGB channels, resulting from ambient light. Using different lightings and color channels 12 images of a single PCB are available. A visual inspection and the investigation of 27 specific points show the best differentiation between those points using a red lighting and a green color channel. Estimating two thresholds from analyzing the multimodal histogram of the corrected images and using them for segmentation precisely extracts the solder joints. The comparison of the results to manually segmented images yield high sensitivity and specificity values. Analyzing the overall result delivers a Dice coefficient of 0.89 which varies for single object segmentations between 0.96 for a good segmented solder joints and 0.25 for single negative outliers. Conclusion: Our results demonstrate that the presented optical imaging system and the developed algorithm can robustly detect solder joints on printed circuit boards. Future work will comprise a modified lighting system which allows for more precise segmentation results using structure analysis.

Keywords: printed circuit board jet-printing, inspection, segmentation, solder paste detection

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