Search results for: genome wide association studies

Authors: John Hardy

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Over the last decade, the increasing utility of extremist narratives to the operational effectiveness of terrorist organizations has been evidenced by the proliferation of inspired or affiliated attacks across the world. Famous examples such as regional al-Qaeda affiliates and the self-styled “Islamic State” demonstrate the effectiveness of leveraging communication technologies to disseminate propaganda, recruit members, and orchestrate attacks. Terrorist organizations with the capacity to harness the communicative power offered by digital communication technologies and effective political narratives have held an advantage over their targets in recent years. Terrorists have leveraged the perceived legitimacy of grass-roots actors to appeal to a global audience of potential supporters and enemies alike, and have wielded a proficiency in profile-raising which remains unmatched by counter terrorism narratives around the world. In contrast, many attempts at propagating official counter-narratives have been received by target audiences as illegitimate, top-down and impersonally bureaucratic. However, the benefits provided by widespread communication and extremist narratives have come at an operational cost. Terrorist organizations now face a significant challenge in protecting their access to communications technologies and authority over the content they create and endorse. The dissemination of effective narratives has emerged as a core function of terrorist organizations with international reach via inspired or affiliated attacks. As such, it has become a critical function which can be targeted by intelligence and security forces. This study applies network targeting principles which have been used by coalition forces against a range of non-state actors in the Middle East and South Asia to the communicative function of terrorist organizations. This illustrates both a conceptual link between functional targeting and operational disruption in the abstract and a tangible impact on the operational effectiveness of terrorists by degrading communicative ability and legitimacy. Two case studies highlight the utility of applying functional targeting against terrorist organizations. The first case is the targeted killing of Anwar al-Awlaki, an al-Qaeda propagandist who crafted a permissive narrative and effective propaganda videos to attract recruits who committed inspired terrorist attacks in the US and overseas. The second is a series of operations against Islamic State propagandists in Syria, including the capture or deaths of a cadre of high profile Islamic State members, including Junaid Hussain, Abu Mohammad al-Adnani, Neil Prakash, and Rachid Kassim. The group of Islamic State propagandists were linked to a significant rise in affiliated and enabled terrorist attacks and were subsequently targeted by law enforcement and military agencies. In both cases, the disruption of communication between the terrorist organization and recruits degraded both communicative and operational functions. Effective functional targeting on member recruitment and operational tempo suggests that narratives are a critical function which can be leveraged against terrorist organizations. Further application of network targeting methods to terrorist narratives may enhance the efficacy of a range of counter terrorism techniques employed by security and intelligence agencies.

Keywords: countering violent extremism, counter terrorism, intelligence, terrorism, violent extremism

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Authors: Paul Licina, Emma M. Johnston, David Lisle, Mark Young, Chris Brady

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Background: Lumbar pars pathology is a common cause of pain in the growing spine. It can be seen in young athletes participating in at-risk sports and can affect sporting performance and long-term health due to its resistance to traditional management. There is a current lack of consensus of classification and treatment for pars injuries. Previous systems used CT to stage pars defects but could not assess early stress reactions. A modified classification is proposed that considers findings on MRI, significantly improving early treatment guidance. The treatment protocol is designed for patients aged 5 to 19 years. Method: Clinical screening identifies patients with a low, medium, or high index of suspicion for lumbar pars injury using patient age, sport participation and pain characteristics. MRI of the at-risk cohort enables augmentation of existing CT-based classification while avoiding ionising radiation. Patients are classified into five categories based on MRI findings. A type 0 lesion (stress reaction) is present when CT is normal and MRI shows high signal change (HSC) in the pars/pedicle on T2 images. A type 1 lesion represents the ‘early defect’ CT classification. The group previously referred to as a 'progressive stage' defect on CT can be split into 2A and 2B categories. 2As have HSC on MRI, whereas 2Bs do not. This distinction is important with regard to healing potential. Type 3 lesions are terminal stage defects on CT, characterised by pseudarthrosis. MRI shows no HSC. Results: Stress reactions (type 0) and acute fractures (1 and 2a) can heal and are treated in a custom-made hard brace for 12 weeks. It is initially worn 23 hours per day. At three weeks, patients commence basic core rehabilitation. At six weeks, in the absence of pain, the brace is removed for sleeping. Exercises are progressed to positions of daily living. Patients with continued pain remain braced 23 hours per day without exercise progression until becoming symptom-free. At nine weeks, patients commence supervised exercises out of the brace for 30 minutes each day. This allows them to re-learn muscular control without rigid support of the brace. At 12 weeks, bracing ceases and MRI is repeated. For patients with near or complete resolution of bony oedema and healing of any cortical defect, rehabilitation is focused on strength and conditioning and sport-specific exercise for the full return to activity. The length of this final stage is approximately nine weeks but depends on factors such as development and level of sports participation. If significant HSC remains on MRI, CT scan is considered to definitively assess cortical defect healing. For these patients, return to high-risk sports is delayed for up to three months. Chronic defects (2b and 3) cannot heal and are not braced, and rehabilitation follows traditional protocols. Conclusion: Appropriate clinical screening and imaging with MRI can identify pars pathology early. In those with potential for healing, we propose hard bracing and appropriate rehabilitation as part of a multidisciplinary management protocol. The validity of this protocol will be tested in future studies.

Keywords: adolescents, MRI classification, pars interticularis, treatment protocol

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Authors: Medan Isaeva, Anna Degtyareva

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Context: Biliary atresia is a common reason for liver transplants in children, and the Kasai procedure can potentially be successful in avoiding the need for transplantation. However, it is important to identify factors that influence surgical outcomes in order to optimize treatment and improve patient outcomes. Research aim: The aim of this study was to develop prognostic models to assess the outcomes of the Kasai procedure in children with biliary atresia. Methodology: This retrospective study analyzed data from 166 children with biliary atresia who underwent the Kasai procedure between 2002 and 2021. The effectiveness of the operation was assessed based on specific criteria, including post-operative stool color, jaundice reduction, and bilirubin levels. The study involved a comparative analysis of various parameters, such as gestational age, birth weight, age at operation, physical development, liver and spleen sizes, and laboratory values including bilirubin, ALT, AST, and others, measured pre- and post-operation. Ultrasonographic evaluations were also conducted pre-operation, assessing the hepatobiliary system and related quantitative parameters. The study was carried out by two experienced specialists in pediatric hepatology. Comparative analysis and multifactorial logistic regression were used as the primary statistical methods. Findings: The study identified several statistically significant predictors of a successful Kasai procedure, including the presence of the gallbladder and levels of cholesterol and direct bilirubin post-operation. A detectable gallbladder was associated with a higher probability of surgical success, while elevated post-operative cholesterol and direct bilirubin levels were indicative of a reduced chance of positive outcomes. Theoretical importance: The findings of this study contribute to the optimization of treatment strategies for children with biliary atresia undergoing the Kasai procedure. By identifying early predictive signs of success, clinicians can modify treatment plans and manage patient care more effectively and proactively. Data collection and analysis procedures: Data for this analysis were obtained from the health records of patients who received the Kasai procedure. Comparative analysis and multifactorial logistic regression were employed to analyze the data and identify significant predictors. Question addressed: The study addressed the question of identifying predictive factors for the success of the Kasai procedure in children with biliary atresia. Conclusion: The developed prognostic models serve as valuable tools for early detection of patients who are less likely to benefit from the Kasai procedure. This enables clinicians to modify treatment plans and manage patient care more effectively and proactively. Potential limitations of the study: The study has several limitations. Its retrospective nature may introduce biases and inconsistencies in data collection. Being single centered, the results might not be generalizable to wider populations due to variations in surgical and postoperative practices. Also, other potential influencing factors beyond the clinical, laboratory, and ultrasonographic parameters considered in this study were not explored, which could affect the outcomes of the Kasai operation. Future studies could benefit from including a broader range of factors.

Keywords: biliary atresia, kasai operation, prognostic model, native liver survival

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Osman Adiguzel

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Shape memory alloys take place in a class of smart materials by exhibiting a peculiar property called the shape memory effect. This property is characterized by the recoverability of two certain shapes of material at different temperatures. These materials are often called smart materials due to their functionality and their capacity of responding to changes in the environment. Shape memory materials are used as shape memory devices in many interdisciplinary fields such as medicine, bioengineering, metallurgy, building industry and many engineering fields. The shape memory effect is performed thermally by heating and cooling after first cooling and stressing treatments, and this behavior is called thermoelasticity. This effect is based on martensitic transformations characterized by changes in the crystal structure of the material. The shape memory effect is the result of successive thermally and stress-induced martensitic transformations. Shape memory alloys exhibit thermoelasticity and superelasticity by means of deformation in the low-temperature product phase and high-temperature parent phase region, respectively. Superelasticity is performed by stressing and releasing the material in the parent phase region. Loading and unloading paths are different in the stress-strain diagram, and the cycling loop reveals energy dissipation. The strain energy is stored after releasing, and these alloys are mainly used as deformation absorbent materials in control of civil structures subjected to seismic events, due to the absorbance of strain energy during any disaster or earthquake. Thermal-induced martensitic transformation occurs thermally on cooling, along with lattice twinning with cooperative movements of atoms by means of lattice invariant shears, and ordered parent phase structures turn into twinned martensite structures, and twinned structures turn into the detwinned structures by means of stress-induced martensitic transformation by stressing the material in the martensitic condition. Thermal induced transformation occurs with the cooperative movements of atoms in two opposite directions, <110 > -type directions on the {110} - type planes of austenite matrix which is the basal plane of martensite. Copper-based alloys exhibit this property in the metastable β-phase region, which has bcc-based structures at high-temperature parent phase field. Lattice invariant shear and twinning is not uniform in copper-based ternary alloys and gives rise to the formation of complex layered structures, depending on the stacking sequences on the close-packed planes of the ordered parent phase lattice. In the present contribution, x-ray diffraction and transmission electron microscopy (TEM) studies were carried out on two copper-based CuAlMn and CuZnAl alloys. X-ray diffraction profiles and electron diffraction patterns reveal that both alloys exhibit superlattice reflections inherited from the parent phase due to the displacive character of martensitic transformation. X-ray diffractograms taken in a long time interval show that diffraction angles and intensities of diffraction peaks change with the aging duration at room temperature. In particular, some of the successive peak pairs providing a special relation between Miller indices come close to each other. This result refers to the rearrangement of atoms in a diffusive manner.

Keywords: shape memory effect, martensitic transformation, reversibility, superelasticity, twinning, detwinning

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Authors: Neil Singla, Derek Muse, Karen DiDonato, Pamela Palmer

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Introduction: Pain is the most common reason people visit emergency rooms. Studies indicate however, that Emergency Department (ED) physicians often do not provide adequate analgesia to their patients as a result of gender and age bias, opiophobia and insufficient knowledge of and formal training in acute pain management. Novel classes of analgesics have recently been introduced, but many patients suffer from acute pain in settings where the availability of intravenous (IV) access may be limited, so there remains a clinical need for rapid-acting, potent analgesics that do not require an invasive route of delivery. A sublingual sufentanil tablet (SST), dispensed using a single-dose applicator, is in development for treatment of moderate-to-severe acute pain in a medically-supervised setting. Objective: The primary objective of this study was to demonstrate the repeat-dose efficacy, safety and tolerability of sufentanil 20 mcg and 30 mcg sublingual tablets compared to placebo for the management of acute pain as determined by the time-weighted sum of pain intensity differences (SPID) to baseline over the 12-hour study period (SPID12). Key secondary efficacy variables included SPID over the first hour (SPID1), Total pain relief over the 12-hour study period (TOTPAR12), time to perceived pain relief (PR) and time to meaningful PR. Safety variables consisted of adverse events (AE), vital signs, oxygen saturation and early termination. Methods: In this Phase 2, double-blind, dose-finding study, an equal number of male and female patients were randomly assigned in a 2:2:1 ratio to SST 20 mcg, SS 30 mcg or placebo, respectively, following bunionectomy. Study drug was dosed as needed, but not more frequently than hourly. Rescue medication was available as needed. The primary endpoint was the Summed Pain Intensity Difference to baseline over 12h (SPIDI2). Safety was assessed by continuous oxygen saturation monitoring and adverse event reporting. Results: 101 patients (51 Male/50 Female) were randomized, 100 received study treatment (intent-to-treat [ITT] population), and 91 completed the study. Reasons for early discontinuation were lack of efficacy (6), adverse events (2) and drug-dosing error (1). Mean age was 42.5 years. For the ITT population, SST 30 mcg was superior to placebo (p=0.003) for the SPID12. SPID12 scores in the active groups were superior for both male (ANOVA overall p-value =0.038) and female (ANOVA overall p-value=0.005) patients. Statistically significant differences in favour of sublingual sufentanil were also observed between the SST 30mcg and placebo group for SPID1(p<0.001), TOTPAR12(p=0.002), time to perceived PR (p=0.023) and time to meaningful PR (p=0.010). Nausea, vomiting and somnolence were more frequent in the sufentanil groups but there were no significant differences between treatment arms for the proportion of patients who prematurely terminated due to AE or inadequate analgesia. Conclusions: Sufentanil tablets dispensed sublingually using a single-dose applicator is in development for treatment of patients with moderate-to-severe acute pain in a medically-supervised setting where immediate IV access is limited. When administered sublingually, sufentanil’s pharmacokinetic profile and non-invasive delivery makes it a useful alternative to IM or IV dosing.

Keywords: acute pain, pain management, sublingual, sufentanil

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Authors: Satish Kumar, Nisha Goyal

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In the stock market, individual investors exhibit different kinds of behaviour. Traditional finance is built on the notion of 'homo economics', which states that humans always make perfectly rational choices to maximize their wealth and minimize risk. That is, traditional finance has concern for how investors should behave rather than how actual investors are behaving. Behavioural finance provides the explanation for this phenomenon. Although finance has been studied for thousands of years, behavioural finance is an emerging field that combines the behavioural or psychological aspects with conventional economic and financial theories to provide explanations on how emotions and cognitive factors influence investors’ behaviours. These emotions and cognitive factors are known as behavioural biases. Because of these biases, investors make irrational investment decisions. Besides, the emotional and cognitive factors, the social influence of media as well as friends, relatives and colleagues also affect investment decisions. Psychological factors influence individual investors’ investment decision making, but few studies have used qualitative methods to understand these factors. The aim of this study is to explore the behavioural factors or biases that affect individuals’ investment decision making. For the purpose of this exploratory study, an in-depth interview method was used because it provides much more exhaustive information and a relaxed atmosphere in which people feel more comfortable to provide information. Twenty investment advisors having a minimum 5 years’ experience in securities firms were interviewed. In this study, thematic content analysis was used to analyse interview transcripts. Thematic content analysis process involves analysis of transcripts, coding and identification of themes from data. Based on the analysis we categorized the statements of advisors into various themes. Past market returns and volatility; preference for safe returns; tendency to believe they are better than others; tendency to divide their money into different accounts/assets; tendency to hold on to loss-making assets; preference to invest in familiar securities; tendency to believe that past events were predictable; tendency to rely on the reference point; tendency to rely on other sources of information; tendency to have regret for making past decisions; tendency to have more sensitivity towards losses than gains; tendency to rely on own skills; tendency to buy rising stocks with the expectation that this rise will continue etc. are some of the major concerns showed by experts about investors. The findings of the study revealed 13 biases such as overconfidence bias, disposition effect, familiarity bias, framing effect, anchoring bias, availability bias, self-attribution bias, representativeness, mental accounting, hindsight bias, regret aversion, loss aversion and herding bias/media biases present in Indian investors. These biases have a negative connotation because they produce a distortion in the calculation of an outcome. These biases are classified under three categories such as cognitive errors, emotional biases and social interaction. The findings of this study may assist both financial service providers and researchers to understand the various psychological biases of individual investors in investment decision making. Additionally, individual investors will also be aware of the behavioural biases that will aid them to make sensible and efficient investment decisions.

Keywords: financial advisors, individual investors, investment decisions, psychological biases, qualitative thematic content analysis

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Authors: Rama Umesh Pandey, Jyoti Yadav

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Flooding is one of the waterborne disasters that causes extensive destruction in urban areas. Developing countries are at a higher risk of such damage and more than half of the global flooding events take place in Asian countries including India. Urban flooding is more of a human-induced disaster rather than natural. This is highly influenced by the anthropogenic factors, besides metrological and hydrological causes. Unplanned urbanization and poor management of cities enhance the impact manifold and cause huge loss of life and property in urban areas. It is an irony that urban areas have been facing water scarcity in summers and flooding during monsoon. This paper is an attempt to highlight the factors responsible for flooding in a city especially from an urban planning perspective and to suggest mitigating measures through spatial planning interventions. Analysis has been done in two stages; first is to assess the impacts of previous flooding events and second to analyze the factors responsible for flooding at macro and micro level in cities. Bhopal, a city in Central India having nearly two million population, has been selected for the study. The city has been experiencing flooding during heavy rains in monsoon. The factors responsible for urban flooding were identified through literature review as well as various case studies from different cities across the world and India. The factors thus identified were analyzed for both macro and micro level influences. For macro level, the previous flooding events that have caused huge destructions were analyzed and the most affected areas in Bhopal city were identified. Since the identified area was falling within the catchment of a drain so the catchment area was delineated for the study. The factors analyzed were: rainfall pattern to calculate the return period using Weibull’s formula; imperviousness through mapping in ArcGIS; runoff discharge by using Rational method. The catchment was divided into micro watersheds and the micro watershed having maximum impervious surfaces was selected to analyze the coverage and effect of physical infrastructure such as: storm water management; sewerage system; solid waste management practices. The area was further analyzed to assess the extent of violation of ‘building byelaws’ and ‘development control regulations’ and encroachment over the natural water streams. Through analysis, the study has revealed that the main issues have been: lack of sewerage system; inadequate storm water drains; inefficient solid waste management in the study area; violation of building byelaws through extending building structures ether on to the drain or on the road; encroachments by slum dwellers along or on to the drain reducing the width and capacity of the drain. Other factors include faulty culvert’s design resulting in back water effect. Roads are at higher level than the plinth of houses which creates submersion of their ground floors. The study recommends spatial planning interventions for mitigating urban flooding and strategies for management of excess rain water during monsoon season. Recommendations have also been made for efficient land use management to mitigate water logging in areas vulnerable to flooding.

Keywords: mitigating strategies, spatial planning interventions, urban flooding, violation of development control regulations

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Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta

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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.

Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.

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Authors: Parth Gupta, Ujjawal Singh, Shashank Kumar, Mansi Chandra, Arnab Sarkar

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Microfluidic devices have emerged as indispensable tools across various scientific disciplines, offering precise control and manipulation of fluids at the microscale. Their efficacy in flow-based research, spanning engineering, chemistry, and biology, relies heavily on the geometric design of microfluidic channels. This work introduces a novel approach to optimise these channels through Response Surface Methodology (RSM), departing from the conventional practice of addressing one parameter at a time. Traditionally, optimising microfluidic channels involved isolated adjustments to individual parameters, limiting the comprehensive understanding of their combined effects. In contrast, our approach considers the simultaneous impact of multiple parameters, employing RSM to efficiently explore the complex design space. The outcome is an innovative microfluidic channel that consumes an optimal sample volume and minimises flow time, enhancing overall efficiency. The relevance of geometric parameter optimization in microfluidic channels extends significantly in biomedical engineering. The flow characteristics of porous materials within these channels depend on many factors, including fluid viscosity, environmental conditions (such as temperature and humidity), and specific design parameters like sample volume, channel width, channel length, and substrate porosity. This intricate interplay directly influences the performance and efficacy of microfluidic devices, which, if not optimized, can lead to increased costs and errors in disease testing and analysis. In the context of biomedical applications, the proposed approach addresses the critical need for precision in fluid flow. it mitigate manufacturing costs associated with trial-and-error methodologies by optimising multiple geometric parameters concurrently. The resulting microfluidic channels offer enhanced performance and contribute to a streamlined, cost-effective process for testing and analyzing diseases. A key highlight of our methodology is its consideration of the interconnected nature of geometric parameters. For instance, the volume of the sample, when optimized alongside channel width, length, and substrate porosity, creates a synergistic effect that minimizes errors and maximizes efficiency. This holistic optimization approach ensures that microfluidic devices operate at their peak performance, delivering reliable results in disease testing. A key highlight of our methodology is its consideration of the interconnected nature of geometric parameters. For instance, the volume of the sample, when optimized alongside channel width, length, and substrate porosity, creates a synergistic effect that minimizes errors and maximizes efficiency. This holistic optimization approach ensures that microfluidic devices operate at their peak performance, delivering reliable results in disease testing. A key highlight of our methodology is its consideration of the interconnected nature of geometric parameters. For instance, the volume of the sample, when optimized alongside channel width, length, and substrate porosity, creates a synergistic effect that minimizes errors and maximizes efficiency. This holistic optimization approach ensures that microfluidic devices operate at their peak performance, delivering reliable results in disease testing.

Keywords: microfluidic device, minitab, statistical optimization, response surface methodology

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Authors: Ok-Kyun Im, Kyoung Hee Kim

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We live in an era that faces global challenges of climate changes and resource depletion. With the rapid urbanization and growing energy consumption in the built environment, building facades become ever more important in architectural practice and environmental stewardship. Furthermore, building facade undergoes complex dynamics of social, cultural, environmental and technological changes. Kinetic facades have drawn attention of architects, designers, and engineers in the field of adaptable, responsive and interactive architecture since 1980’s. Materials and building technologies have gradually evolved to address the technical implications of kinetic facades. The kinetic façade is becoming an independent system of the building, transforming the design methodology to sustainable building solutions. Accordingly, there is a need for a new design methodology to guide the design of a kinetic façade and evaluate its sustainable performance. The research objectives are two-fold: First, to establish a new design methodology for kinetic facades and second, to develop a micro-oculi façade system and assess its performance using the established design method. The design approach to the micro-oculi facade is comprised of 1) façade geometry optimization and 2) dynamic building energy simulation. The façade geometry optimization utilizes multi-objective optimization process, aiming to balance the quantitative and qualitative performances to address the sustainability of the built environment. The dynamic building energy simulation was carried out using EnergyPlus and Radiance simulation engines with scripted interfaces. The micro-oculi office was compared with an office tower with a glass façade in accordance with ASHRAE 90.1 2013 to understand its energy efficiency. The micro-oculi facade is constructed with an array of circular frames attached to a pair of micro-shades called a micro-oculus. The micro-oculi are encapsulated between two glass panes to protect kinetic mechanisms with longevity. The micro-oculus incorporates rotating gears that transmit the power to adjacent micro-oculi to minimize the number of mechanical parts. The micro-oculus rotates around its center axis with a step size of 15deg depending on the sun’s position while maximizing daylighting potentials and view-outs. A 2 ft by 2ft prototyping was undertaken to identify operational challenges and material implications of the micro-oculi facade. In this research, a systematic design methodology was proposed, that integrates multi-objectives of kinetic façade design criteria and whole building energy performance simulation within a holistic design process. This design methodology is expected to encourage multidisciplinary collaborations between designers and engineers to collaborate issues of the energy efficiency, daylighting performance and user experience during design phases. The preliminary energy simulation indicated that compared to a glass façade, the micro-oculi façade showed energy savings due to its improved thermal properties, daylighting attributes, and dynamic solar performance across the day and seasons. It is expected that the micro oculi façade provides a cost-effective, environmentally-friendly, sustainable, and aesthetically pleasing alternative to glass facades. Recommendations for future studies include lab testing to validate the simulated data of energy and optical properties of the micro-oculi façade. A 1:1 performance mock-up of the micro-oculi façade can suggest in-depth understanding of long-term operability and new development opportunities applicable for urban façade applications.

Keywords: energy efficiency, kinetic facades, sustainable architecture, urban facades

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Authors: Adiba Matin, Daniel Cabrera, Javiera Bellolio, Jasmine Stewart, Dana Gerberi (librarian), Nathan Cummins, Fernanda Bellolio

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OBJECTIVES: Artificial intelligence (AI) tools are becoming more prevalent in healthcare settings, particularly for diagnostic and therapeutic recommendations, with an expected surge in the incoming years. The bedside use of this technology for clinicians opens the possibility of disagreements between the recommendations from AI algorithms and clinicians’ judgment. There is a paucity in the literature analyzing nature and possible outcomes of these potential conflicts, particularly related to ethical considerations. The goal of this scoping review is to identify, analyze and classify current themes and potential strategies addressing ethical conflicts originating from the conflict between AI and human recommendations. METHODS: A protocol was written prior to the initiation of the study. Relevant literature was searched by a medical librarian for the terms of artificial intelligence, healthcare and liability, ethics, or conflict. Search was run in 2021 in Ovid Cochrane Central Register of Controlled Trials, Embase, Medline, IEEE Xplore, Scopus, and Web of Science Core Collection. Articles describing the role of AI in healthcare that mentioned conflict between humans and AI were included in the primary search. Two investigators working independently and in duplicate screened titles and abstracts and reviewed full-text of potentially eligible studies. Data was abstracted into tables and reported by themes. We followed methodological guidelines for Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). RESULTS: Of 6846 titles and abstracts, 225 full texts were selected, and 48 articles included in this review. 23 articles were included as original research and review papers. 25 were included as editorials and commentaries with similar themes. There was a lack of consensus in the included articles on who would be held liable for mistakes incurred by following AI recommendations. It appears that there is a dichotomy of the perceived ethical consequences depending on if the negative outcome is a result of a human versus AI conflict or secondary to a deviation from standard of care. Themes identified included transparency versus opacity of recommendations, data bias, liability of outcomes, regulatory framework, and the overall scope of artificial intelligence in healthcare. A relevant issue identified was the concern by clinicians of the “black box” nature of these recommendations and the ability to judge appropriateness of AI guidance. CONCLUSION AI clinical tools are being rapidly developed and adopted, and the use of this technology will create conflicts between AI algorithms and healthcare workers with various outcomes. In turn, these conflicts may have legal, and ethical considerations. There is limited consensus about the focus of ethical and liability for outcomes originated from disagreements. This scoping review identified the importance of framing the problem in terms of conflict between standard of care or not, and informed by the themes of transparency/opacity, data bias, legal liability, absent regulatory frameworks and understanding of the technology. Finally, limited recommendations to mitigate ethical conflicts between AI and humans have been identified. Further work is necessary in this field.

Keywords: ethics, artificial intelligence, emergency medicine, review

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Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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Authors: Michele Paleologo, Marta Acampora, Serena Barello, Guendalina Graffigna

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Introduction: In the face of increasing demands for higher agricultural productivity with minimal environmental impact, participatory research approaches emerge as promising means to promote innovation. However, the complexities and ambiguities surrounding these approaches in both theory and practice present challenges. This Scoping Review seeks to bridge these gaps by mapping participatory approaches in agricultural contexts, analyzing their characteristics, and identifying indicators of success. Methods: Following PRISMA guidelines, we conducted a systematic Scoping Review, searching Scopus and Web of Science databases. Our review encompassed 34 projects from diverse geographical regions and farming contexts. Thematic analysis was employed to explore the types of innovation promoted and the categories of participants involved. Results: The identified innovation types encompass technological advancements, sustainable farming practices, and market integration, forming 5 main themes: climate change, cultivar, irrigation, pest and herbicide, and technical improvement. These themes represent critical areas where participatory research drives innovation to address pressing agricultural challenges. Participants were categorized as citizens, experts, NGOs, private companies, and public bodies. Understanding their roles is vital for designing effective participatory initiatives that embrace diverse stakeholders. The review also highlighted 27 theoretical frameworks underpinning participatory projects. Clearer guidelines and reporting standards are crucial for facilitating the comparison and synthesis of findings across studies, thereby enhancing the robustness of future participatory endeavors. Furthermore, we identified three main categories of barriers and facilitators: pragmatic/behavioral, emotional/relational, and cognitive. These insights underscore the significance of participant engagement and collaborative decision-making for project success beyond theoretical considerations. Regarding participation, projects were classified as contributory (5 cases), where stakeholders contributed insights; collaborative (10 cases), with active co-designing of solutions; and co-created (19 cases), featuring deep stakeholder involvement from ideation to implementation, resulting in joint ownership of outcomes. Such diverse participation modes highlight the adaptability of participatory approaches to varying agricultural contexts. Discussion: In conclusion, this Scoping Review demonstrates the potential of participatory research in driving transformative changes in farmers' practices, fostering sustainability and innovation in agriculture. Understanding the diverse landscape of participatory approaches, theoretical frameworks, and participant engagement strategies is essential for designing effective and context-specific interventions. Collaborative efforts among researchers, practitioners, and stakeholders are pivotal in harnessing the full potential of participatory approaches and driving positive change in agricultural settings worldwide. The identified themes of innovation and participation modes provide valuable insights for future research and targeted interventions in agricultural innovation.

Keywords: participatory research, co-creation, agricultural innovation, stakeholders' engagement

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Authors: Miguel García-Ferrús, Yolanda Domínguez, M Angeles Castillo, M Antonia Ferrús, Ana Jiménez-Belenguer

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Antibiotic resistance is a growing public health concern worldwide, and it is now regarded as a critical issue within the "One Health" approach that affects human and animal health, agriculture, and environmental waste management. This concept focuses on the interconnected nature of human, animal and environmental health, and WHO highlights zoonotic diseases, food safety, and antimicrobial resistance as three particularly relevant areas for this framework. Fresh vegetables are garnering attention in the food chain due to the presence of pathogens and because they can act as a reservoir for Antibiotic Resistance Bacteria (ARB) and Antibiotic Resistance Genes (ARG). These fresh products are frequently consumed raw, thereby contributing to the spread and transmission of antibiotic resistance. Therefore, the aim of this research was to study the microbiological quality, the prevalence of ARB, and their role in the dissemination of ARG in fresh vegetables intended for human consumption. For this purpose, 102 samples of fresh vegetables (30 lettuce, 30 cabbage, 18 strawberries and 24 spinach) from different retail establishments in Valencia (Spain) have been analyzed to determine their microbiological quality and their role in spreading ARB and ARG. The samples were collected and examined according to standardized methods for total viable bacteria, coliforms, Shiga toxin-producing Escherichia coli (STEC), Listeria monocytogenes and Salmonella spp. Isolation was made in culture media supplemented with antibiotics (cefotaxime and meropenem). A total of 239 strains resistant to beta-lactam antibiotics (Third-Generation Cephalosporins and Carbapenems) were isolated. Thirty Gram-negative isolates were selected and biochemically identified or partial sequencing of 16S rDNA. Their sensitivity to 12 antibiotic discs was determined using the Kirby-Bauer disc diffusion technique to different therapeutic groups. To determine the presence of ARG, PCR assays for the direct sample and selected isolate DNA were performed for main expanded spectrum beta-lactamase (ESBL)-, carbapenemase-encoding genes and plasmid-mediated quinolone resistance genes. From the total samples, 68% (24/24 spinach, 28/30 lettuce and 17/30 cabbage) showed total viable bacteria levels over the accepted standard 10(2)-10(5) cfu/g range; and 48% (24/24 spinach, 19/30 lettuce and 6/30) showed coliforms levels over the accepted standard 10(2)-10(4) cfu/g range. In 9 samples (3/24 spinach, 3/30 lettuce, 3/30 cabbage; 9/102 (9%)) E. coli levels were higher than the standard 10(3) cfu/g limit. Listeria monocytogenes, Salmonella and STEC have not been detected. Six different bacteria species were isolated from samples. Stenotrophomonas maltophilia (64%) was the prevalent species, followed by Acinetobacter pitii (14%) and Burkholderia cepacia (7%). All the isolates were resistant to at least one tested antibiotic, including meropenem (85%) and ceftazidime (46%). Of the total isolates, 86% were multidrug-resistant and 68% were ESBL productors. Results of PCR showed the presence of resistance genes to beta-lactams blaTEM (4%) and blaCMY-2 (4%), to carbapenemes blaOXA-48 (25%), blaVIM (7%), blaIMP (21%) and blaKPC (32%), and to quinolones QnrA (7%), QnrB (11%) and QnrS (18%). Thus, fresh vegetables harboring ARB and ARG constitute a potential risk to consumers. Further studies must be done to detect ARG and how they propagate in non-medical environments.

Keywords: ESBL, β-lactams, resistances, fresh vegetables.

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Authors: Iryna P. Dzieciuch, Michael D. Putman

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Humidity is known to degrade Navy ship electronic equipment, especially in hot moist environments. If left untreated, it can cause significant and permanent damage. Even rigorous inspection and frequent clean-up would not prevent further equipment contamination and degradation because of the constant presence of favorable growth conditions for many microorganisms. Generally, relative humidity levels of less than 60% will inhibit corrosion in electronic equipment, but because NAVY electronics often operate in hot and humid environments, prevention via dehumidification is not always possible. Currently, there is no defined research that fully describes key mechanisms which cause electronics and its coating degradation. The corrosive action of most bacteria is mainly developed through (i) mycelium adherence to the metal plates, (ii) facilitation the formation of pitting areas, (iii) production of organic acids such as citric, iso-citric, cis-aconitic, alpha-ketoglutaric, which are corrosive to electronic equipment and its components. Our approach studies corrosive action in electronic equipment: circuit-board, wires and connections that are exposed in the humid environment that gets worse during condensation. In our new approach the technical task is built on work with the bacterial communities in public areas, bacterial genetics, bioinformatics, biostatistics and Scanning Electron Microscopy (SEM) of corroded circuit boards. Based on these methods, we collect and examine environmental samples from biofilms of the corroded and non-corroded sites, where bacterial contamination of electronic equipment, such as machine racks and shore boats, is an ongoing concern. Sample collection and sample analysis is focused on addressing the key questions identified above through the following tasks: laboratory sample processing and evaluation under scanning electron microscopy, initial sequencing and data evaluation; bioinformatics and data analysis. Preliminary results from scanning electron microscopy (SEM) have revealed that metal particulates and alloys in corroded samples consists mostly of Tin ( < 40%), Silicon ( < 4%), Sulfur ( < 1%), Aluminum ( < 2%), Magnesium ( < 2%), Copper ( < 1%), Bromine ( < 2%), Barium ( <1%) and Iron ( < 2%) elements. We have also performed X 12000 magnification of the same sites and that proved existence of undisrupted biofilm organelles and crystal structures. Non-corrosion sites have revealed high presence of copper ( < 47%); other metals remain at the comparable level as on the samples with corrosion. We have performed X 1000 magnification on the non-corroded at the sites and have documented formation of copper crystals. The next step of this study, is to perform metagenomics sequencing at all sites and to compare bacterial composition present in the environment. While copper is nontoxic to the living organisms, the process of bacterial adhesion creates acidic environment by releasing citric, iso-citric, cis-aconitic, alpha-ketoglutaric acidics, which in turn release copper ions Cu++, which that are highly toxic to the bacteria and higher order living organisms. This phenomenon, might explain natural “antibiotic” properties that are lacking in elements such as tin. To prove or deny this hypothesis we will use next - generation sequencing (NGS) methods to investigate types and growth cycles of bacteria that from bacterial biofilm the on corrosive and non-corrosive samples.

Keywords: bacteria, biofilm, circuit board, copper, corrosion, electronic equipment, organic acids, tin

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Authors: Annette Louise Dupont

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Background and Introduction: Broadly defined, hybridity is a condition of racial and cultural ‘cross-pollination’ which arises as a result of contact between colonized and colonizer. It remains a highly contested concept in postcolonial studies as it is implicitly underpinned by colonial notions of ‘racial purity.’ While some postcolonial scholars argue that individuals exercise significant agency in the construction of their hybrid subjectivities, others underscore associated experiences of exclusion, marginalization, and alienation. Kuwait and the Philippines are among the most disparate of contemporary postcolonial states. While oil resources transformed the former British Mandate of Kuwait into one of the world’s richest countries, enduring poverty in the former US colony of the Philippines drives a global diaspora which produces multiple Filipino hybridities. Although more Filipinos work in the Arabian Gulf than in any other region of the world, scholarly and literary accounts of their experiences of hybridization in this region are relatively scarce when compared to those set in North America, Australia, Asia, and Europe. Study Aims and Significance: This paper aims to address this existing lacuna by investigating hybridity and other postcolonial themes in a novel by a Kuwaiti author which vividly portrays the lives of immigrants and citizens in Kuwait and which gives a rare voice and insight into the struggles of an Arab-Filipino and European-Filipina. Specifically, this paper explores the relationships between colonial discourses of ‘black’ and ‘white’ and postcolonial discourses pertaining to ‘brown’ Filipinos and ‘brown’ Arabs, in order to assess their impacts on the protagonists’ hybrid subjectivities. Methodology: Foucault’s notions of discourse not only provide a conceptual basis for analyzing the colonial ideology of Orientalism, but his theories related to the social exclusion of the ‘mad’ also elucidate the mechanisms by which power can operate to marginalize, alienate and subjectify the Other, therefore a Foucauldian lens is applied to the analysis of postcolonial themes and hybrid subjectivities portrayed in the novel. Findings: The study finds that Kuwaiti and Filipino discursive practices mirror those of former white colonialists and colonized black laborers and that these discursive practices combine with a former British colonial system of foreign labor sponsorship to create a form of governmentality in Kuwait which is based on exclusion and control. The novel’s rich social description and the reflections of the key protagonist and narrator suggest that such fiction has a significant role to play in highlighting the historical and cultural specificities of experiences of postcolonial hybridity in under-researched geographic, economic, social, and political settings. Whereas hybridity can appear abstract in scholarly accounts, the significance of literary accounts in which the lived experiences of hybrid protagonists are anchored to specific historical periods, places and discourses, is that contextual particularities are neither obscured nor dehistoricized. Conclusions: The application of Foucauldian theorizations of discourse, disciplinary, and biopower to the analysis of this Kuwaiti literary text serves to extend an understanding of the effects of contextually-specific discourses on hybrid Filipino subjectivities, as well as a knowledge of prevailing social dynamics in a little-researched postcolonial Arabian Gulf state.

Keywords: Filipino, Foucault, hybridity, Kuwait

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Authors: Justine Salam

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As a federal state, Canada’s constitutional arrangements regarding the management of natural resources is unique because it gives complete ownership and control of natural resources to the provinces (subnational level). However, the province of Alberta—home to the third largest oil reserves in the world—lags behind comparable jurisdictions in levying royalties on oil corporations, especially oil sands royalties. While Albertans own the oil sands, scholars have argued that natural resource exploitation in Alberta benefits corporations and industry more than it does Albertans. This study provides a systematic understanding of the causal factors affecting royalties in Alberta to map dynamics of power and how they manifest themselves during policy-making. Mounting domestic and global public pressure led Alberta to review its oil sands royalties twice in less than a decade through public-commissioned Royalty Review Panels, first in 2007 and again in 2015. The Panels’ task was to research best practices and to provide policy recommendations to the Government through public consultations with Albertans, industry, non-governmental organizations, and First Nations peoples. Both times, the Panels recommended a relative increase to oil sands royalties. However, irrespective of the Reviews’ recommendations, neither the right-wing 2007 Progressive Conservative Party (PC) nor the left-wing 2015 New Democratic Party (NDP) government—both committed to increase oil sands royalties—increased royalty intake. Why did two consecutive political parties at opposite ends of the political spectrum fail to account for the recommendations put forward by the Panel? Through a qualitative case-study analysis, this study assesses domestic and global causal factors for Alberta’s inability to raise oil sands royalties significantly after the two Reviews through an institutions, interests, and ideas framework. Indeed, causal factors can be global (e.g. market and price fluctuation) or domestic (e.g. oil companies’ influence on the Alberta government). The institutions, interests, and ideas framework is at the intersection of public policy, comparative studies, and political economy literatures, and therefore draws multi-faceted insights into the analysis. To account for institutions, the study proposes to review international trade agreements documents such as the North American Free Trade Agreement (NAFTA) because they have embedded Alberta’s oil sands into American energy security policy and tied Canadian and Albertan oil policy in legal international nods. To account for interests, such as how the oil lobby or the environment lobby can penetrate governmental decision-making spheres, the study draws on the Oil Sands Oral History project, a database of interviews from government officials and oil industry leaders at a pivotal time in Alberta’s oil industry, 2011-2013. Finally, to account for ideas, such as how narratives of Canada as a global ‘energy superpower’ and the importance of ‘energy security’ have dominated and polarized public discourse, the study relies on content analysis of Alberta-based pro-industry newspapers to trace the prevalence of these narratives. By mapping systematically the nods and dynamics of power at play in Alberta, the study sheds light on the factors that influence royalty policy-making in one of the largest industries in Canada.

Keywords: Alberta Canada, natural resources governance, oil sands, political economy

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Authors: Maria Karnachoriti, Ellas Spyratou, Dimitrios Lykidis, Maria Lambropoulou, Yiannis S. Raptis, Ioannis Seimenis, Efstathios P. Efstathopoulos, Athanassios G. Kontos

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Colorectal cancer is the third most common cancer diagnosed in Europe, according to the latest incidence data provided by the World Health Organization (WHO), and early diagnosis has proved to be the key in reducing cancer-related mortality. In cases where surgical interventions are required for cancer treatment, the accurate discrimination between healthy and cancerous tissues is critical for the postoperative care of the patient. The current study focuses on the ex vivo handling of surgically excised colorectal specimens and the acquisition of their spectral fingerprints using Raman spectroscopy. Acquired data were analyzed in an effort to discriminate, in microscopic scale, between healthy and malignant margins. Raman spectroscopy is a spectroscopic technique with high detection sensitivity and spatial resolution of few micrometers. The spectral fingerprint which is produced during laser-tissue interaction is unique and characterizes the biostructure and its inflammatory or cancer state. Numerous published studies have demonstrated the potential of the technique as a tool for the discrimination between healthy and malignant tissues/cells either ex vivo or in vivo. However, the handling of the excised human specimens and the Raman measurement conditions remain challenging, unavoidably affecting measurement reliability and repeatability, as well as the technique’s overall accuracy and sensitivity. Therefore, tissue handling has to be optimized and standardized to ensure preservation of cell integrity and hydration level. Various strategies have been implemented in the past, including the use of balanced salt solutions, small humidifiers or pump-reservoir-pipette systems. In the current study, human colorectal specimens of 10X5 mm were collected from 5 patients up to now who underwent open surgery for colorectal cancer. A novel, non-toxic zinc-based fixative (Z7) was used for tissue preservation. Z7 demonstrates excellent protein preservation and protection against tissue autolysis. Micro-Raman spectra were recorded with a Renishaw Invia spectrometer from successive random 2 micrometers spots upon excitation at 785 nm to decrease fluorescent background and secure avoidance of tissue photodegradation. A temperature-controlled approach was adopted to stabilize the tissue at 2 °C, thus minimizing dehydration effects and consequent focus drift during measurement. A broad spectral range, 500-3200 cm-1,was covered with five consecutive full scans that lasted for 20 minutes in total. The average spectra were used for least square fitting analysis of the Raman modes.Subtle Raman differences were observed between normal and cancerous colorectal tissues mainly in the intensities of the 1556 cm-1 and 1628 cm-1 Raman modes which correspond to v(C=C) vibrations in porphyrins, as well as in the range of 2800-3000 cm-1 due to CH2 stretching of lipids and CH3 stretching of proteins. Raman spectra evaluation was supported by histological findings from twin specimens. This study demonstrates that Raman spectroscopy may constitute a promising tool for real-time verification of clear margins in colorectal cancer open surgery.

Keywords: colorectal cancer, Raman spectroscopy, malignant margins, spectral fingerprints

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Authors: Muhammad Haris, Syed Kamran Ali, Mubeen Islam, Tariq Mehmood, Faisal Shah

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Jacobabad Khairpur High, part of a Sukkur rift zone, is the separating boundary between Central and Southern Indus Basin, formed as a result of Post-Jurassic uplift after the deposition of Middle Jurassic Chiltan Formation. Habib Rahi Formation of Middle to Late Eocene outcrops in the vicinity of Jacobabad Khairpur High, a section at Rohri near Sukkur is measured in detail for lithofacies, microfacies, diagenetic analysis and sequence stratigraphy. Habib Rahi Formation is richly fossiliferous and consists of mostly limestone with subordinate clays and marl. The total thickness of the formation in this section is 28.8m. The bottom of the formation is not exposed, while the upper contact with the Sirki Shale of the Middle Eocene age is unconformable in some places. A section is measured using Jacob’s Staff method, and traverses were made perpendicular to the strike. Four different lithofacies were identified based on outcrop geology which includes coarse-grained limestone facies (HR-1 to HR-5), massive bedded limestone facies (HR-6 HR-7), and micritic limestone facies (HR-8 to HR-13) and algal dolomitic limestone facie (HR-14). Total 14 rock samples were collected from outcrop for detailed petrographic studies, and thin sections of respective samples were prepared and analyzed under the microscope. On the basis of Dunham’s (1962) classification systems after studying textures, grain size, and fossil content and using Folk’s (1959) classification system after reviewing Allochems type, four microfacies were identified. These microfacies include HR-MF 1: Benthonic Foraminiferal Wackstone/Biomicrite Microfacies, HR-MF 2: Foramineral Nummulites Wackstone-Packstone/Biomicrite Microfacies HR-MF 3: Benthonic Foraminiferal Packstone/Biomicrite Microfacies, HR-MF 4: Bioclasts Carbonate Mudstone/Micrite Microfacies. The abundance of larger benthic Foraminifera’s (LBF), including Assilina sp., A. spiral abrade, A. granulosa, A. dandotica, A. laminosa, Nummulite sp., N. fabiani, N. stratus, N. globulus, Textularia, Bioclasts, and Red algae indicates shallow marine (Tidal Flat) environment of deposition. Based on variations in rock types, grain size, and marina fauna Habib Rahi Formation shows progradational stacking patterns, which indicates coarsening upward cycles. The second order of sea-level rise is identified (spanning from Y-Persian to Bartonian age) that represents the Transgressive System Tract (TST) and a third-order Regressive System Tract (RST) (spanning from Bartonian to Priabonian age). Diagenetic processes include fossils replacement by mud, dolomitization, pressure dissolution associated stylolites features and filling with dark organic matter. The presence of the microfossils includes Nummulite. striatus, N. fabiani, and Assilina. dandotica, signify Bartonian to Priabonian age of Habib Rahi Formation.

Keywords: Jacobabad Khairpur High, Habib Rahi Formation, lithofacies, microfacies, sequence stratigraphy, diagenetic history

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Authors: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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Authors: Catherine Vasnetsov, Victor Vasnetsov

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Context: Thermo-responsive polymers are materials that undergo significant changes in their physical properties in response to temperature changes. These polymers have gained significant attention in research due to their potential applications in various industries and medicine. However, the molecular mechanisms underlying their behavior are not well understood, particularly in relation to cosolvency, which is crucial for practical applications. Research Aim: This study aimed to theoretically investigate the phenomenon of cosolvency in long-chain polymers using the Flory-Huggins statistical-mechanical framework. The main objective was to understand the interactions between the polymer, solvent, and cosolvent under different conditions. Methodology: The research employed a combination of Monte Carlo computer simulations and advanced machine-learning methods. The Flory-Huggins mean field theory was used as the basis for the simulations. Spinodal graphs and ternary plots were utilized to develop an initial computer model for predicting polymer behavior. Molecular dynamic simulations were conducted to mimic real-life polymer systems. Machine learning techniques were incorporated to enhance the accuracy and reliability of the simulations. Findings: The simulations revealed that the addition of very low or very high volumes of cosolvent molecules resulted in smaller radii of gyration for the polymer, indicating poor miscibility. However, intermediate volume fractions of cosolvent led to higher radii of gyration, suggesting improved miscibility. These findings provide a possible microscopic explanation for the cosolvency phenomenon in polymer systems. Theoretical Importance: This research contributes to a better understanding of the behavior of thermo-responsive polymers and the role of cosolvency. The findings provide insights into the molecular mechanisms underlying cosolvency and offer specific predictions for future experimental investigations. The study also presents a more rigorous analysis of the Flory-Huggins free energy theory in the context of polymer systems. Data Collection and Analysis Procedures: The data for this study was collected through Monte Carlo computer simulations and molecular dynamic simulations. The interactions between the polymer, solvent, and cosolvent were analyzed using the Flory-Huggins mean field theory. Machine learning techniques were employed to enhance the accuracy of the simulations. The collected data was then analyzed to determine the impact of cosolvent volume fractions on the radii of gyration of the polymer. Question Addressed: The research addressed the question of how cosolvency affects the behavior of long-chain polymers. Specifically, the study aimed to investigate the interactions between the polymer, solvent, and cosolvent under different volume fractions and understand the resulting changes in the radii of gyration. Conclusion: In conclusion, this study utilized theoretical modeling and computer simulations to investigate the phenomenon of cosolvency in long-chain polymers. The findings suggest that moderate cosolvent volume fractions can lead to improved miscibility, as indicated by higher radii of gyration. These insights contribute to a better understanding of the molecular mechanisms underlying cosolvency in polymer systems and provide predictions for future experimental studies. The research also enhances the theoretical analysis of the Flory-Huggins free energy theory.

Keywords: molecular modelling, flory-huggins, cosolvency, stimuli-responsive polymers

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Authors: Melissa de Zeeuw, Peter Smolianov, Arnold Bohl

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This study was designed to help and improve international performance as well increase swimming participation in the Netherlands. Over 200 sources of literature on sport delivery systems from 28 Australasian, North and South American, Western and Eastern European countries were analyzed to construct a globally applicable model of high performance swimming integrated with mass participation, comprising of the following seven elements and three levels: Micro level (operations, processes, and methodologies for development of individual athletes): 1. Talent search and development, 2. Advanced athlete support. Meso level (infrastructures, personnel, and services enabling sport programs): 3. Training centers, 4. Competition systems, 5. Intellectual services. Macro level (socio-economic, cultural, legislative, and organizational): 6. Partnerships with supporting agencies, 7. Balanced and integrated funding and structures of mass and elite sport. This model emerged from the integration of instruments that have been used to analyse and compare national sport systems. The model has received scholarly validation and showed to be a framework for program analysis that is not culturally bound. It has recently been accepted as a model for further understanding North American sport systems, including (in chronological order of publications) US rugby, tennis, soccer, swimming and volleyball. The above model was used to design a questionnaire of 42 statements reflecting desired practices. The statements were validated by 12 international experts, including executives from sport governing bodies, academics who published on high performance and sport development, and swimming coaches and administrators. In this study both a highly structured and open ended qualitative analysis tools were used. This included a survey of swim coaches where open responses accompanied structured questions. After collection of the surveys, semi-structured discussions with Federation coaches were conducted to add triangulation to the findings. Lastly, a content analysis of Dutch Swimming’s website and organizational documentation was conducted. A representative sample of 1,600 Dutch Swim coaches and administrators was collected via email addresses from Royal Dutch Swimming Federation' database. Fully completed questionnaires were returned by 122 coaches from all key country’s regions for a response rate of 7,63% - higher than the response rate of the previously mentioned US studies which used the same model and method. Results suggest possible enhancements at macro level (e.g., greater public and corporate support to prepare and hire more coaches and to address the lack of facilities, monies and publicity at mass participation level in order to make swimming affordable for all), at meso level (e.g., comprehensive education for all coaches and full spectrum of swimming pools particularly 50 meters long), and at micro level (e.g., better preparation of athletes for a future outside swimming and better use of swimmers to stimulate swimming development). Best Dutch swimming management practices (e.g., comprehensive support to most talented swimmers who win Olympic medals) as well as relevant international practices available for transfer to the Netherlands (e.g., high school competitions) are discussed.

Keywords: sport development, high performance, mass participation, swimming

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Authors: Deon Bezuidenhout

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Pre-seeding with autologous endothelial cells improves the long-term patency of synthetic vascular grafts levels obtained with autografts, but is limited to a single centre due to resource, time and other constraints. Spontaneous in vivo endothelialization would obviate the need for pre-seeding, but has been shown to be absent in man due to limited transanastomotic and fallout healing, and the lack of transmural ingrowth due to insufficient porosity. Two types of graft scaffolds with increased interconnected porosity for improved tissue ingrowth and healing are thus proposed and described. Foam-type polyurethane (PU) scaffolds with small, medium and large, interconnected pores were made by phase inversion and spherical porogen extraction, with and without additional surface modification with covalently attached heparin and subsequent loading with and delivery of growth factors. Fibrillar scaffolds were made either by standard electrospinning using degradable PU (Degrapol®), or by dual electrospinning using non-degradable PU. The latter process involves sacrificial fibres that are co-spun with structural fibres and subsequently removed to increased porosity and pore size. Degrapol samples were subjected to in vitro degradation, and all scaffold types were evaluated in vivo for tissue ingrowth and vascularization using rat subcutaneous model. The foam scaffolds were additionally evaluated in a circulatory (rat infrarenal aortic interposition) model that allows for the grafts to be anastomotically and/or ablumenally isolated to discern and determine endothelialization mode. Foam-type grafts with large (150 µm) pores showed improved subcutaneous healing in terms of vascularization and inflammatory response over smaller pore sizes (60 and 90µm), and vascularization of the large porosity scaffolds was significantly increased by more than 70% by heparin modification alone, and by 150% to 400% when combined with growth factors. In the circulatory model, extensive transmural endothelialization (95±10% at 12 w) was achieved. Fallout healing was shown to be sporadic and limited in groups that were ablumenally isolated to prevent transmural ingrowth (16±30% wrapped vs. 80±20% control; p<0.002). Heparinization and GF delivery improved both mural vascularization and lumenal endothelialization. Degrapol electrospun scaffolds showed decrease in molecular mass and corresponding tensile strength over the first 2 weeks, but very little decrease in mass over the 4w test period. Studies on the effect of tissue ingrowth with and without concomitant degradation of the scaffolds, are being used to develop material models for the finite element modelling. In the case of the dual-spun scaffolds, the PU fibre fraction could be controlled shown to vary linearly with porosity (P = −0.18FF +93.5, r2=0.91), which in turn showed inverse linear correlation with tensile strength and elastic modulus (r2 > 0.96). Calculated compliance and burst pressures of the scaffolds increased with fibre fraction, and compliances matching the human popliteal artery (5-10 %/100 mmHg), and high burst pressures (> 2000 mmHg) could be achieved. Increasing porosity (76 to 82 and 90%) resulted in increased tissue ingrowth from 33±7 to 77±20 and 98±1% after 28d. Transmural endothelialization of highly porous foamed grafts is achievable in a circulatory model, and the enhancement of porosity and tissue ingrowth may hold the key the development of spontaneously endothelializing electrospun grafts.

Keywords: electrospinning, endothelialization, porosity, scaffold, vascular graft

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

Abstract:

The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: M. Mueller, M. Kuehn, M. Voelker

Abstract:

In small and medium-sized enterprises (SMEs), the challenge is to create a well-grounded and reliable basis for process analysis, optimization and planning due to a lack of data. SMEs have limited access to methods with which they can effectively and efficiently analyse processes and identify cause-and-effect relationships in order to generate the necessary database and derive optimization potential from it. The implementation of digitalization within the framework of Industry 4.0 thus becomes a particular necessity for SMEs. For these reasons, the abstract presents an analysis methodology that is subject to the objective of developing an SME-appropriate methodology for efficient, temporarily feasible data collection and evaluation in flexible production and logistics systems as a basis for process analysis and optimization. The overall methodology focuses on retrospective, event-based tracing and analysis of material flow objects. The technological basis consists of Bluetooth low energy (BLE)-based transmitters, so-called beacons, and smart mobile devices (SMD), e.g. smartphones as receivers, between which distance data can be measured and derived motion profiles. The distance is determined using the Received Signal Strength Indicator (RSSI), which is a measure of signal field strength between transmitter and receiver. The focus is the development of a software-based methodology for interpretation of relative movements of transmitters and receivers based on distance data. The main research is on selection and implementation of pattern recognition methods for automatic process recognition as well as methods for the visualization of relative distance data. Due to an existing categorization of the database regarding process types, classification methods (e.g. Support Vector Machine) from the field of supervised learning are used. The necessary data quality requires selection of suitable methods as well as filters for smoothing occurring signal variations of the RSSI, the integration of methods for determination of correction factors depending on possible signal interference sources (columns, pallets) as well as the configuration of the used technology. The parameter settings on which respective algorithms are based have a further significant influence on result quality of the classification methods, correction models and methods for visualizing the position profiles used. The accuracy of classification algorithms can be improved up to 30% by selected parameter variation; this has already been proven in studies. Similar potentials can be observed with parameter variation of methods and filters for signal smoothing. Thus, there is increased interest in obtaining detailed results on the influence of parameter and factor combinations on data quality in this area. The overall methodology is realized with a modular software architecture consisting of independently modules for data acquisition, data preparation and data storage. The demonstrator for initialization and data acquisition is available as mobile Java-based application. The data preparation, including methods for signal smoothing, are Python-based with the possibility to vary parameter settings and to store them in the database (SQLite). The evaluation is divided into two separate software modules with database connection: the achievement of an automated assignment of defined process classes to distance data using selected classification algorithms and the visualization as well as reporting in terms of a graphical user interface (GUI).

Keywords: event-based tracing, machine learning, process classification, parameter settings, RSSI, signal smoothing

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Authors: Abderrazak Bannari

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Acid Mine Drainage (AMD) from mine wastes and contaminations of soils and water with metals are considered as a major environmental problem in mining areas. It is produced by interactions of water, air, and sulphidic mine wastes. This environment problem results from a series of chemical and biochemical oxidation reactions of sulfide minerals e.g. pyrite and pyrrhotite. These reactions lead to acidity as well as the dissolution of toxic and heavy metals (Fe, Mn, Cu, etc.) from tailings waste rock piles, and open pits. Soil and aquatic ecosystems could be contaminated and, consequently, human health and wildlife will be affected. Furthermore, secondary minerals, typically formed during weathering of mine waste storage areas when the concentration of soluble constituents exceeds the corresponding solubility product, are also important. The most common secondary mineral compositions are hydrous iron oxide (goethite, etc.) and hydrated iron sulfate (jarosite, etc.). The objectives of this study focus on the detection and mapping of MIOP in the soil using Hyperion EO-1 (Earth Observing - 1) hyperspectral data and constrained linear spectral mixture analysis (CLSMA) algorithm. The abandoned Kettara mine, located approximately 35 km northwest of Marrakech city (Morocco) was chosen as study area. During 44 years (from 1938 to 1981) this mine was exploited for iron oxide and iron sulphide minerals. Previous studies have shown that Kettara surrounding soils are contaminated by heavy metals (Fe, Cu, etc.) as well as by secondary minerals. To achieve our objectives, several soil samples representing different MIOP classes have been resampled and located using accurate GPS ( ≤ ± 30 cm). Then, endmembers spectra were acquired over each sample using an Analytical Spectral Device (ASD) covering the spectral domain from 350 to 2500 nm. Considering each soil sample separately, the average of forty spectra was resampled and convolved using Gaussian response profiles to match the bandwidths and the band centers of the Hyperion sensor. Moreover, the MIOP content in each sample was estimated by geochemical analyses in the laboratory, and a ground truth map was generated using simple Kriging in GIS environment for validation purposes. The acquired and used Hyperion data were corrected for a spatial shift between the VNIR and SWIR detectors, striping, dead column, noise, and gain and offset errors. Then, atmospherically corrected using the MODTRAN 4.2 radiative transfer code, and transformed to surface reflectance, corrected for sensor smile (1-3 nm shift in VNIR and SWIR), and post-processed to remove residual errors. Finally, geometric distortions and relief displacement effects were corrected using a digital elevation model. The MIOP fraction map was extracted using CLSMA considering the entire spectral range (427-2355 nm), and validated by reference to the ground truth map generated by Kriging. The obtained results show the promising potential of the proposed methodology for the detection and mapping of mine iron oxide pollution in the soil.

Keywords: hyperion eo-1, hyperspectral, mine iron oxide pollution, environmental impact, unmixing

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Authors: Sakshi Chopra, Ashima Nehra, Sumit Sinha, Harsimarpreet Kaur, Ravindra Mohan Pandey

Abstract:

Background: Cognitive rehabilitation aims to retrain brain injured individuals with cognitive deficits to restore or compensate lost functions. As illiterates or people with low literacy levels represent a significant proportion of the world, specific rehabilitation modules for such populations are indispensable. Literacy is significantly associated with all neuropsychological measures and retraining programs widely use written or spoken techniques which essentially require the patient to read or write. So, the aim of the study was to develop and standardize a literacy free neuropsychological rehabilitation program for improving cognitive functioning in patients with mild and moderate Traumatic Brain Injury (TBI). Several studies have pointed out to the impairments seen in memory, executive functioning, and attention and concentration post-TBI, so the rehabilitation program focussed on these domains. Visual item memorization, stick constructions, symbol cancellations, and colouring techniques were used to construct the retraining program. Methodology: The development of the program consisted of planning, preparing, analyzing, and revising the different modules. The construction focussed on areas of retraining immediate and delayed visual memory, planning ability, focused and divided attention, concentration, and response inhibition (to control irritability and aggression). A total of 98 home based retraining modules were prepared in the 4 domains (42 for memory, 42 for executive functioning, 7 for attention and concentration, and 7 for response inhibition). The standardization was done on 20 healthy controls to review, select and edit items. For each module, the time, errors made and errors per second were noted down, to establish the difficulty level of each module and were arranged in increasing level of difficulty over a period of 6 weeks. The retraining tasks were then administered on 11 brain injured individuals (5 after Mild TBI and 6 after Moderate TBI). These patients were referred from the Trauma Centre to Clinical Neuropsychology OPD, All India Institute of Medical Sciences, New Delhi, India. Results: The time was taken, errors made and errors per second were analysed for all domains. Education levels were divided into illiterates, up to 10 years, 10 years to graduation and graduation and above. Mean and standard deviations were calculated. Between group and within group analysis was done using the t-test. The performance of 20 healthy controls was analyzed and only a significant difference was observed on the time taken for the attention tasks and all other domains had non-significant differences in performance between different education levels. Comparing the errors, time taken between patient and control group, there was a significant difference in all the domains at the 0.01 level except the errors made on executive functioning, indicating that the tool can successfully differentiate between healthy controls and patient groups. Conclusions: Apart from the time taken for symbol cancellations, the entire cognitive rehabilitation program is literacy free. As it taps the major areas of impairment post-TBI, it could be a useful tool to rehabilitate the patient population with low literacy levels across the world. The next step is already underway to test its efficacy in improving cognitive functioning in a randomized clinical controlled trial.

Keywords: cognitive rehabilitation, illiterates, India, traumatic brain injury

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Authors: Vijay Samuel, Tina Thekkekkara, Shoma Ganguly

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There is no reported Hanta Seoul virus infection in children in the UK so far, making it quite challenging for clinicians in diagnosing, predicting and prognosticating the outcome of the infection to patients and parents. We report a case of a ten-year-old girl who presented with pyrexia associated with headache, photophobia and abdominal pain. The family had recently acquired two pet rats six weeks ago. She appeared flushed with peri-oral pallor, coated the strawberry tongue, inflamed tonsils and bilateral cervical lymphadenopathy. Her liver and splenic edges were palpable. Investigations showed that she was thrombocytopenic with deranged renal and liver functions. An ultrasound abdomen demonstrated a mildly enlarged spleen, peripancreatic lymph node and an acalculous cholecystitis. In view of her clinical presentation, a diagnosis of leptospirosis was considered and she was commenced on intravenous benzylpenicillin. The following day she became oliguric, developed significant proteinuria and her renal function deteriorated. Following conservative management, her urine output gradually improved along with her renal function, proteinuria and thrombocytopaenia. Serology for leptospirosis and various other viruses were negative. Following discussion with the Rare and Imported Pathogens Laboratory at Porton hanta virus serology was requested and found to be strongly positive for Seoul hanta virus. Following discharge she developed palpitations, fatigue, severe headache and cognitive difficulties including memory loss and difficulties in spelling, reading and mathematics. Extensive investigations including ECG, MRI brain and CSF studies were performed and revealed no significant abnormalities. Since 2012, there have been six cases of acute kidney injury due to Hantavirus infection in the UK. Two cases were from the Humber region and were exposure to wild rats and the other four were exposed to specially bred pet fancy rats. Hanta virus infections can cause mild flu like symptoms but two clinical syndromes are associated with severe disease including haemorrhagic fever with renal syndrome, which may be associated with thrombocytopenia and Hantavirus cardiopulmonary syndrome. Neuropsychological impairments reported following hantavirus pulmonary syndrome and following Puumala virus infection have been reported. Minor white matter lesions were found in about half of the patients investigated with MRI brain. Seoul virus has a global distribution owing to the dispersal of its carrier host rats, through global trade. Several ports in the region could explain the possible establishment of Seoul virus in local populations of rats in the Yorkshire and Humber region. The risk of infection for occupationally exposed groups is 1-3% compared to 32.9% for specialist pet rat owners. The report highlight’s the importance of routinely asking about pets in the family. We hope to raise awareness of the emergence of hantavirus infection in the UK, particularly in the Yorkshire and Humber region. Clinicians should consider hantavirus infection as a potential cause of febrile illness causing renal impairment in children. Awareness of the possible neuro-cognitive sequele would help the clinicians offer appropriate information and support to children and their families. Contacting Rare and Imported Pathogens Laboratory at Porton is a useful resource for clinicians in UK when they consider unusual infections.

Keywords: Seoul hantavirus in child Porton, UK Acute kidney injury

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Authors: Jelena Maletkovic

Abstract:

Background: Endogenous Cushing’s syndrome is a rare disease, but iatrogenic or drug related Cushing syndrome from glucocorticoid products is commonly seen in clinical practice. With high dose and long term use of glucocorticoids, patients can develop isolated hypothalamic-pituitary-adrenal (HPA) suppression, or HPA axis suppression can be accompanied by overt iatrogenic Cushing’s syndrome. This is a rare case where severe Cushing’s syndrome developed from an unknown medication and was followed by severe and prolonged adrenal insufficiency and multiple potentially fatal complications. Case: This is a 37-year-old woman who is presented to Emergency Room (ER) with shortness of breath and chest pain. Four months prior to this presentation the patient was a generally healthy woman who was looking for improvement in her appearance and visited local Rejuvenation Clinic. After initial consultation with a nurse, she was contacted by a physician over the phone and was advised to start taking multiple injectable medications that will arrive by mail. Medications without any labels on bottles were delivered and the patient started daily intramuscular injections. Over the next two months, she noticed rounding of her face and swelling around her eyes. She gained 20 pounds, mostly abdominal fat and became extremely fatigued. Her muscles on legs were visibly decreasing in size and she felt significant muscle weakness. Unexplained bruising occurred. She started growing hair on face and developed secondary amenorrhea. New severe back pain started. She developed depression and headaches. Finally, over a few days, a number of red-purple stretch marks that were sensitive and painful appeared over her abdomen, upper part of arms and legs. She then became suspicious that these dramatic symptoms are caused by injectable medication and she discontinued injections. Over the next few days she presented to ER with low blood pressure and oxygen saturation of 75%. Studies revealed extensive pneumonia as well as multiple pulmonary emboli. Her white blood count was elevated with 32 000 and she also had acute kidney failure on admission. She was treated for sepsis and was also given stress dose steroids. Steroids were tapered over 48 hours and discontinued. After being discharged to home, on her first visit to endocrinology clinic she had undetectable ACTH of < 2pg/mL and undetectable 8am cortisol of < 0.2mcg/dL. She did not respond to an intramuscular injection of cosyntropin 250mcg and her repeated cortisol after 60 minutes was only 1mcg/dL. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone 20mg+10mg. It took close to 2 years of slow tapering for recovery of this patient’s HPA axis and resolve all the sequelae from Cushing’s syndrome. Conclusion: Misuse and abuse of glucocorticoids have been present almost since these medications were discovered. This is a rare case where not only severe Cushing’s syndrome in full clinical picture developed but also the patient suffered multiple potentially fatal complications and prolonged adrenal insufficiency. Visits to herbal, rejuvenation, esthetic, and similar clinics are becoming more and more popular and physicians need to be aware of possible non-benign nature of medications that their patients may be using.

Keywords: iatrogenic, Cushing's syndrome, adrenal crisis, steroid abuse

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