Search results for: Kendrick Thomas Angelo Santos

Authors: Bright Chukwunwike Uzuegbunam, Wojciech Paslawski, Hans Agren, Christer Halldin, Wolfgang Weber, Markus Luster, Thomas Arzberger, Behrooz Hooshyar Yousefi

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There is a need to develop a PET tracer that will enable to diagnosis and track the progression of Alpha-synucleinopathies (Parkinson’s disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA]) in living subjects over time. Alpha-synuclein aggregates (a-syn), which are present in all the stages of disease progression, for instance, in PD, are a suitable target for in vivo PET imaging. For this reason, we have developed some promising a-syn tracers based on a disarylbisthiazole (DABTA) scaffold. The precursors are synthesized via a modified Hantzsch thiazole synthesis. The precursors were then radiolabeled via one- or two-step radiofluorination methods. The ligands were initially screened using a combination of molecular dynamics and quantum/molecular mechanics approaches in order to calculate the binding affinity to a-syn (in silico binding experiments). Experimental in vitro binding assays were also performed. The ligands were further screened in other experiments such as log D, in vitro plasma protein binding & plasma stability, biodistribution & brain metabolite analyses in healthy mice. Radiochemical yields were up to 30% - 72% in some cases. Molecular docking revealed possible binding sites in a-syn and also the free energy of binding to those sites (-28.9 - -66.9 kcal/mol), which correlated to the high binding affinity of the DABTAs to a-syn (Ki as low as 0.5 nM) and selectivity (> 100-fold) over Aβ and tau, which usually co-exist with a-synin some pathologies. The log D values range from 2.88 - 2.34, which correlated with free-protein fraction of 0.28% - 0.5%. Biodistribution experiments revealed that the tracers are taken up (5.6 %ID/g - 7.3 %ID/g) in the brain at 5 min (post-injection) p.i., and cleared out (values as low as 0.39 %ID/g were obtained at 120 min p.i. Analyses of the mice brain 20 min p.i. Revealed almost no radiometabolites in the brain in most cases. It can be concluded that in silico study presents a new venue for the rational development of radioligands with suitable features. The results obtained so far are promising and encourage us to further validate the DABTAs in autoradiography, immunohistochemistry, and in vivo imaging in non-human primates and humans.

Keywords: alpha-synuclein aggregates, alpha-synucleinopathies, PET imaging, tracer development

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

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

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

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Authors: Gilda Santos, Rita Marques, Francisca Marques, João Ribeiro, André Fonseca, João M. Miranda, João B. L. M. Campos, Soraia F. Neves

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Every year, an unacceptable number of firefighters are seriously burned during firefighting operations, with some of them eventually losing their life. Although thermal protective clothing research and development has been searching solutions to minimize firefighters heat load and skin burns, currently commercially available solutions focus in solving isolated problems, for example, radiant heat or water-vapor resistance. Therefore, episodes of severe burns and heat strokes are still frequent. Taking this into account, a consortium composed by Portuguese entities has joined synergies to develop an innovative protective clothing system by following a procedure based on the application of numerical models to optimize the design and using a combinationof protective clothing components disposed in different layers. Recently, it has been shown that Phase Change Materials (PCMs) can contribute to the reduction of potential heat hazards in fire extinguish operations, and consequently, their incorporation into firefighting protective clothing has advantages. The greatest challenge is to integrate these materials without compromising garments ergonomics and, at the same time, accomplishing the International Standard of protective clothing for firefighters – laboratory test methods and performance requirements for wildland firefighting clothing. The incorporation of PCMs into the firefighter's protective jacket will result in the absorption of heat from the fire and consequently increase the time that the firefighter can be exposed to it. According to the project studies and developments, to favor a higher use of the PCM storage capacityand to take advantage of its high thermal inertia more efficiently, the PCM layer should be closer to the external heat source. Therefore, in this stage, to integrate PCMs in firefighting clothing, a mock-up of a vest specially designed to protect the torso (back, chest and abdomen) and to be worn over a fire-resistant jacketwas envisaged. Different configurations of PCMs, as well as multilayer approaches, were studied using suitable joining technologies such as bonding, ultrasound, and radiofrequency. Concerning firefighter’s protective clothing, it is important to balance heat protection and flame resistance with comfort parameters, namely, thermaland water-vapor resistances. The impact of the most promising solutions regarding thermal comfort was evaluated to refine the performance of the global solutions. Results obtained with experimental bench scale model and numerical simulation regarding the integration of PCMs in a vest designed as protective clothing for firefighters will be presented.

Keywords: firefighters, multilayer system, phase change material, thermal protective clothing

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Authors: Rafal Bryk, Holger Schmidt, Thomas Mull, Ingo Ganzmann, Oliver Herbst

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Prediction of the two-phase water mixture level during fast depressurization of the Reactor Pressure Vessel (RPV) resulting from an accident scenario is an important issue from the view point of the reactor safety. Since the level swell may influence the behavior of some passive safety systems, it has been recognized that an assumption which at the beginning may be considered as a conservative one, not necessary leads to a conservative result. This paper discusses outcomes obtained during simulations of the water dynamics and heat transfer during sudden depressurization of a vessel filled up to a certain level with liquid water under saturation conditions and with the rest of the vessel occupied by saturated steam. In case of the pressure decrease e.g. due to the main steam line break, the liquid water evaporates abruptly, being a reason thereby, of strong transients in the vessel. These transients and the sudden emergence of void in the region occupied at the beginning by liquid, cause elevation of the two-phase mixture. In this work, several models calculating the water collapse and swell levels are presented and validated against experimental data. Each of the models uses different approach to calculate void fraction. The object-oriented models were developed with the Modelica modelling language and the OpenModelica environment. The models represent the RPV of the Integral Test Facility Karlstein (INKA) – a dedicated test rig for simulation of KERENA – a new Boiling Water Reactor design of Framatome. The models are based on dynamic mass and energy equations. They are divided into several dynamic volumes in each of which, the fluid may be single-phase liquid, steam or a two-phase mixture. The heat transfer between the wall of the vessel and the fluid is taken into account. Additional heat flow rate may be applied to the first volume of the vessel in order to simulate the decay heat of the reactor core in a similar manner as it is simulated at INKA. The comparison of the simulations results against the reference data shows a good agreement.

Keywords: boiling water reactor, level swell, Modelica, RPV depressurization, thermal-hydraulics

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Authors: Mary Carmen Peloche Barrera

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Since its early years as an independent nation, the United States has been one of the main promoters regarding the recognition, legislation, and protection of human rights. In the matter of freedom, the founding father Thomas Jefferson envisioned the role of the U.S. as a defender of freedom and equality throughout the world. This founding ideal shaped America’s domestic and foreign policy in the 19th and the 20th century and became an aspiration of the ideals of the country to expand its values and institutions. The history of the emergence of human rights cannot be studied without making reference to leaders such as Woodrow Wilson, Franklin, and Eleanor Roosevelt, as well as Martin Luther King. Throughout its history, this country has proclaimed that the protection of the freedoms of men, both inside and outside its borders, is practically the reason for its existence. Although the United States was one of the first countries to recognize the existence of inalienable rights for individuals, as well as the main promoter of the Universal Declaration of Human Rights of 1948, the country has gone through critical moments that had led to questioning its commitment to the issue. Racial segregation, international military interventions, national security strategy, as well as national legislation on immigration, are some of the most controversial issues related to decisions and actions driven by the United States, which at the same time mismatched with its role as an advocate of human rights, both in the Americas and in the rest of the world. The aim of this paper is to study the swinging of the efforts and commitments of the United States towards human rights. The paper will analyze the history and evolution of human rights in the United States, to study the greatest challenges for the country in this matter. The paper will focus on both the domestic policy (related to demographic issues) and foreign policy (about its role in a post-war world). Currently, more countries are joining the multilateral efforts for the promotion and protection of human rights. At the same time, the United States is one of the least committed countries in this respect, having ratified only 5 of the 18 treaties emanating from the United Nations. The last ratification was carried out in 2002 and, since then, the country has been losing ground, in an increasingly vertiginous way, in its credibility and, even worse, in its role as leader of 'the free world'. With or without the United States, the protection of human rights should remain the main goal of the international community.

Keywords: United States, human rights, foreign policy, domestic policy

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Authors: Bindhiya Thomas, Rehana Hafeez

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Background: The Surgical Ambulatory Unit (SAU) also known as the Same Day Emergency Care (SDEC) is an established part of many hospitals providing same day emergency care service to surgical patients who would have otherwise required admission through the A&E. Prior to Covid, the SAU was functioning as a 12-hour service, but during the Covid crisis this service was transformed to a 24 hour functioning Surgical Ambulatory Assessment unit (SAAU). We studied the effects that this change brought about in-patient care in our hospital. Objective: The objective of the study was to assess the impact of a 24-hour Surgical Ambulatory Assessment unit on patient care during the time of Covid, in particular its role in freeing A&E capacity and delivering effective patient care. Methods: We collected two sets of data retrospectively. The first set was collected over a 6-week period when the SAU was functioning at the Princess Royal University Hospital. On March 23rd, 2020, the SAU was transformed into a 24-hour SAAU. Following this transformation, a second set of patient data was collected over a period of 6 weeks. A comparison was made between data collected from when the hospital had a 12-hour Surgical Ambulatory unit and later when it was transformed into a 24-hour facility. Its effects on the change in the number of patients breaching the four hour waiting period and the number of emergency surgical admissions. Results: The 24-hour Surgical Ambulatory Assessment unit brought significant reductions in the number of patients breaching the waiting period of 4 hours in A&E from 44% during the period of the 12-hour Surgical Ambulatory care facility to 0% from when the 24-hour Surgical Ambulatory Assessment Unit was established. A 28% reduction was also seen in the number of surgical patients' admissions from A&E. Conclusions: The 24-hour SAAU was found to have a profound positive impact on emergency care of surgical patients. Especially during the Covid crisis, it played a crucial role in providing not only effective and accessible patient care but also in reducing the A&E workload and admissions. It thus proved to be a strategic tool that helped to deal with the immense workload in emergency care during the Covid crisis and helped free much needed headspace at a time of uncertainty for the A&E to better configure their services. If sustained, the 24-hour SAAU could be relied on to augment the NHS emergency services in the future, especially in the event of another crisis.

Keywords: Princess Royal University Hospital, surgical ambulatory assessment unit, surgical ambulatory unit, same day emergency care

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Authors: Thomas Suarez, Anne-Sophie Grenouilleau, Erwan Autin, Alexandre Biosse-Duplan, Emmanuelle Blondet, Laurence Chazalette, Marie Coniel, Agnes Dessaigne, Sylvie Lascols, Andrea Lasserre, Candice Legris, Pierre Liot, Aline Metais, Karine Petitprez, Christophe Varlet, Christian Saout

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Background: The role of biological sex and gender identity -whether assigned or chosen- as health determinants are far from a recent discovery: several reports have stressed out how being a woman or a man could affect health on various scales. However, taking it into consideration beyond stereotypes and rigid binary assumptions still seems to be a work in progress. Method: The report is a synthesis on a variety of specific topics, each of which was studied by a specialist from the French National Authority for Health (HAS), through an analysis of existing literature on both healthcare policy construction process and instruments (norms, data analysis, clinical trials, guidelines, and professional practices). This work also implied a policy analysis of French recent public health laws and a retrospective study of guidelines with a gender mainstreaming approach. Results: The analysis showed that though sex and gender were well-known determinants of health, their consideration by both public policy and health operators was often incomplete, as it does not incorporate how sex and gender interact, as well as how they interact with other factors. As a result, the health and social care systems and their professionals tend to reproduce some stereotypical and inadequate habits. Though the data available often allows to take sex and gender into consideration, such data is often underused in practice guidelines and policy formulation. Another consequence is a lack of inclusiveness towards transgender or intersex persons. Conclusions: This report first urges for raising awareness of all the actors of health, in its broadest definition, that sex and gender matter beyond first-look conclusions. It makes a series of recommendations in order to reshape policy construction in the health sector on the one hand and to design public health instruments to make them more inclusive regarding sex and gender on the other hand. The HAS finally committed to integrate sex and gender preoccupations in its workings methods, to be a driving force in the spread of these concerns.

Keywords: biological sex, determinants of health, gender, healthcare policy instruments, social accompaniment

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Authors: Florian Misoc, Cyril Okhio, Joshua Tolbert, Nick Carlin, Thomas Ramey

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This project is focused on designing a Stirling engine system for a solar-thermal-electrical system that can supply electric power to a single residential unit. Since Stirling engines are heat engines operating any available heat source, is notable for its ability to generate clean and reliable energy without emissions. Due to the need of finding alternative energy sources, the Stirling engines are making a comeback with the recent technologies, which include thermal energy conservation during the heat transfer process. Recent reviews show mounting evidence and positive test results that Stirling engines are able to produce constant energy supply that ranges from 5kW to 20kW. Solar Power source is one of the many uses for Stirling engines. Using solar energy to operate Stirling engines is an idea considered by many researchers, due to the ease of adaptability of the Stirling engine. In this project, the Stirling engine developed was designed and tested to operate from biomass source of energy, i.e., wood pellets stove, during low solar radiation, with good results. A 20% efficiency of the engine was estimated, and 18% efficiency was measured, making it suitable and appropriate for residential applications. The effort reported was aimed at exploring parameters necessary to design, build and test a ‘Solar Powered Stirling Engine (SPSE)’ using Water (H₂O) as the Heat Transfer medium, with Nitrogen as the working gas that can reach or exceed an efficiency of 20%. The main objectives of this work consisted in: converting a V-twin cylinder air compressor into an alpha-type Stirling engine, construct a Solar Water Heater, by using an automotive radiator as the high-temperature reservoir for the Stirling engine, and an array of fixed mirrors that concentrate the solar radiation on the automotive radiator/high-temperature reservoir. The low-temperature reservoir is the surrounding air at ambient temperature. This work has determined that a low-cost system is sufficiently efficient and reliable. Off-the-shelf components have been used and estimates of the ability of the Engine final design to meet the electricity needs of small residence have been determined.

Keywords: stirling engine, solar-thermal, power inverter, alternator

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Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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Authors: Thomas Chinedu Aniokete, Gordian Onyebuchukwu Mbah, Michael Daramola

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A sustainable NaOH integrated hydrothermal protocol was developed for the synthesis of waste-derived hydroxy sodalite catalysts for transesterification of waste animal fat (WAF) with a high per cent free fatty acid (FFA) to biodiesel. In this work, hydroxy sodalite catalyst was synthesized from two complex waste materials namely coal fly ash (CFA) and waste industrial brine (WIB). Measured amounts of South African CFA and WIB obtained from a coal mine field were mixed with NaOH solution at different concentrations contained in secured glass vessels equipped with magnetic stirrers and formed consistent slurries after aging condition at 47 oC for 48 h. The slurries were then subjected to hydrothermal treatments at 140 oC for 48 h, washed thoroughly and separated by the action of a centrifuge on the mixture. The resulting catalysts were calcined in a muffle furnace for 2 h at 200 oC and subsequently characterized for different effects using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), and Bennett Emmet Teller (BET) adsorption-desorption techniques. The produced animal fat methyl ester (AFME) was analyzed using the gas chromatography-mass spectrometry (GC-MS) method. Results of the investigation indicate profoundly an enhanced catalyst purity, textural property and desired morphology due to the action of NaOH. Similarly, the performance evaluation with respect to catalyst activity reveals a high catalytic conversion efficiency of 98 % of the high FFA WAF to biodiesel under the following reaction conditions; a methanol-to-WAF ratio of 15:1, amount of SOD catalyst of 3 wt % with a stirring speed of 300-500 rpm, a reaction temperature of 60 oC and a reaction time of 8 h. There was a recovered 96 % stable catalyst after reactions and potentially recyclable, thus contributing to the economic savings to the process that had been a major bottleneck to the production of biodiesel. This NaOH route for synthesizing waste-derived hydroxy sodalite (SOD) catalyst is a sustainable and eco-friendly technology that speaks directly to the global quest for renewable-fossil fuel controversy enforcing sustainable development goal 7.

Keywords: coal fly ash, waste industrial brine, waste-derived hydroxy sodalite catalyst, sodium hydroxide, biodiesel, transesterification, biomass conversion

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Authors: Rammah Abdlbagi, Egmen Tazcan, Kiriti Tripathi, Vinayagam Sudhakar, Thomas Swallow, Aakash Pai

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Introduction and Objectives: MRI has an increasing role in the diagnosis and staging of prostate cancer. Multiparametric MRI includes multiple sequences, including T2 weighting, diffusion weighting, and dynamic contrast enhancement (DCE). Administration of DCE is expensive, time-consuming, and requires medical supervision due to the risk of anaphylaxis. Biparametric MRI (bpMRI), without DCE, overcomes many of these issues; however, there is conflicting data on its accuracy. Furthermore, data on the concordance between bpMRI lesion and pathology specimen, as well as the rates of cancer stage upgrading after surgery, is limited within the available literature. This study aims to examine the diagnostic test accuracy of bpMRI in the diagnosis of prostate cancer and radiological assessment of prostate cancer staging. Specifically, we aimed to evaluate the ability of bpMRI to accurately localise malignant lesions to better understand its accuracy and application in MRI-targeted biopsies. Materials and Methods: One hundred and forty patients who underwent bpMRI prior to radical prostatectomy (RP) were retrospectively reviewed from a single institution. Histological grade from the prostate biopsy was compared with surgical specimens from RP. Clinically significant prostate cancer (csPCa) was defined as Gleason grade group ≥2. bpMRI staging was compared with RP histology. Results: Overall sensitivity of bpMRI in diagnosing csPCa independent of location and staging was 98.87%. Of the 140 patients, 29 (20.71%) had their prostate biopsy histology upgraded at RP. 61 (43.57%) patients had csPca noted on RP specimens in areas that were not identified on the bpMRI. 55 (39.29%) had upstaging after RP from the original staging with bpMRI. Conclusions: Whilst the overall sensitivity of bpMRI in predicting any clinically significant cancer was good, there was notably poor concordance in the location of the tumour between bpMRI and eventual RP specimen. The results suggest that caution should be exercised when using bpMRI for targeted prostate biopsies and validates the continued role of systemic biopsies. Furthermore, a significant number of patients were upstaged at RP from their original staging with bpMRI. Based on these findings, bpMRI results should be interpreted with caution and can underestimate TNM stage, requiring careful consideration of treatment strategy.

Keywords: biparametric MRI, Ca prostate, staging, post prostatectomy histology

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Authors: Wei-Shan Wang, Klaus Vogel, Felix Gabler, Maik Wiemer, Thomas Gessner

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Metallic glasses, which are free of grain boundaries, have superior properties including large elastic limits, high strength, and excellent wear and corrosion resistance. Therefore, bulk metallic glasses (BMG) and thin film metallic glasses (TFMG) have been widely developed and investigated. Among various kinds of metallic glasses, Pd-Cu-Si TFMG, which has lower elastic modulus and better resistance of oxidation and corrosions compared to Zr- and Fe-based TFMGs, can be a promising candidate for MEMS applications. However, the study of Pd-TFMG membrane is still limited. This paper presents free-standing Pd-based metallic glass membranes with large area fabricated on wafer level for the first time. Properties of Pd-Cu-Si thin film metallic glass (TFMG) with various deposition parameters are investigated first. When deposited at 25°C, compressive stress occurs in the Pd76Cu6Si18 thin film regardless of Ar pressure. When substrate temperature is increased to 275°C, the stress state changes from compressive to tensile. Thin film stresses are slightly decreased when Ar pressure is higher. To show the influence of temperature on Pd-TFMGs, thin films without and with post annealing below (275°C) and within (370°C) supercooled liquid region are investigated. Results of XRD and TEM analysis indicate that Pd-TFMGs remain amorphous structure with well-controlled parameters. After verification of amorphous structure of the Pd-TFMGs, free-standing Pd-Cu-Si membranes were fabricated by depositing Pd-Cu-Si thin films directly on 200nm-thick silicon nitride membranes, followed by post annealing and dry etching of silicon nitride layer. Post annealing before SiNx removal is used to further release internal stress of Pd-TFMGs. The edge length of the square membrane ranges from 5 to 8mm. The effect of post annealing on Pd-Cu-Si membranes are discussed as well. With annealing at 370°C for 5 min, Pd-MG membranes are fully distortion-free after removal of SiNx layer. Results show that, by introducing annealing process, the stress-relief, distortion-free Pd-TFMG membranes with large area can be a promising candidate for sensing applications such as pressure and gas sensors.

Keywords: amorphous alloy, annealing, metallic glasses, TFMG membrane

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Authors: Portia Murphy, Danica Vasic, Anoja W. Gunaratne, Encarnita Sitchon, Teresita Tugonon, Marou Ison, Antoinette Le Busque, Christelle Pagonis, Thomas J. Borody

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Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder that affects an estimated 11% of the population globally with the most predominant symptoms being abdominal pain, bloating and altered bowel movements. All age groups suffer from IBS although the prevalence of IBS decreases for age groups over 50 years. Women are more likely to suffer from IBS than men. IBS can be categorized into 3 groups based on the type of altered bowel movement: diarrhea-predominant IBS (IBS-D), constipation-predominant IBS (IBS-C) and IBS with mixed bowel habit (IBS-M). The contribution of the gut microbiome to the etiology of IBS is becoming increasingly recognized with rising use of anti-microbial agents. Previous studies on vancomycin and rifaximin used as monotherapy or in combination have been conducted mainly on IBS-C and showed marked improvements in the symptoms. According to our knowledge, no studies reported using these two combinations of antibiotics for IBS-D. Here, we report a consecutive cohort of 18 patients treated with both vancomycin and rifaximin for IBS-D. These patients’ records were reviewed retrospectively. In this cohort, patients ages were between 24-74 years (mean 44 years) and 9 were female. Baseline all patients had diarrhea, 4 with mucus and one with blood. Patients reported other symptoms were abdominal pain (n=11) bloating (n=9), flatulence (n=7), fatigue (n=4) and nausea (n=3). Patients treatments were personalized according to their symptom severity and tolerability and were treated with combination of rifaximin (500 - 3000mg/d) and vancomycin (500mg - 1500mg/d) for an ongoing period. Follow-ups were conducted between 2-32 weeks’ time. Of all patients, 89% patients reported improvement of the symptoms, 1 reported no change and 1 patient’s symptoms got worse. The mechanism of action for both vancomycin and rifaximin involves the inhibition of bacterial cell wall and protein synthesis respectively. The role of these medications in improving the symptoms of this cohort suggests that IBS-D may be microbiome infection driven. In this cohort, similar patient presentations to Clostridium difficile, as well as symptom improvement with the use of rifaximin and particularly vancomycin, suggest that the infectious agent may be an unidentified Clostridium. These preliminary results offer an alternative etiology for IBS-D not previously considered and open the avenue for new research.

Keywords: clostridium deficile, diarrhea predominant Irritable Bowel Syndrome, microbiome, vancomycin/rifaximin combination

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Authors: Syed A. Bukhari, Ankur Goswmai, Dale Hume, Thomas Thundat

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Here we demonstrate mechanical detection of photo-induced Insulator to metal transition (MIT) in ultra-thin vanadium dioxide (VO₂) micro strings by using < 100 µW of optical power. Highly focused laser beam heated the string locally resulting in through plane and along axial heat diffusion. Localized temperature increase can cause temperature rise > 60 ºC. The heated region of VO₂ can transform from insulating (monoclinic) to conducting (rutile) phase leading to lattice compressions and stiffness increase in the resonator. The mechanical frequency of the resonator can be tuned by changing optical power and wavelength. The first mode resonance frequency was tuned in three different ways. A decrease in frequency below a critical optical power, a large increase between 50-120 µW followed by a large decrease in frequency for optical powers greater than 120 µW. The dynamic mechanical response was studied as a function of incident optical power and gas pressure. The resonance frequency and amplitude of vibration were found to be decreased with increasing laser power from 25-38 µW and increased by1-2 % when the laser power was further increased to 52 µW. The transition in films was induced and detected by a single pump and probe source and by employing external optical sources of different wavelengths. This trend in dynamic parameters of the strings can be co-related with reversible Insulator to metal transition in VO₂ films which creates change in density of the material and hence the overall stiffness of the strings leading to changes in string dynamics. The increase in frequency at a particular optical power manifests a transition to a more ordered metallic phase which tensile stress onto the string. The decrease in frequency at higher optical powers can be correlated with poor phonon thermal conductivity of VO₂ in conducting phase. Poor thermal conductivity of VO₂ can force in-plane penetration of heat causing the underneath SiN supporting VO₂ which can result as a decrease in resonance frequency. This noninvasive, non-contact laser-based excitation and detection of Insulator to metal transition using micro strings resonators at room temperature and with laser power in few µWs is important for low power electronics, and optical switching applications.

Keywords: thermal conductivity, vanadium dioxide, MEMS, frequency tuning

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Authors: Christina Klippel, Lucia Pezzi, Silvio Neto, Rafael Bertani, Priscila Mendes, Flavio Machado, Aline Szeliga, Maria Cosendey, Adilson Mariz, Raquel Santos, Lys Bendett, Pedro Velasco, Thalita Rolleigh, Bruna Bellote, Daria Coelho, Bruna Martins, Julia Almeida, Juliana Cerqueira

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This project presents a framework for teaching intracranial pressure monitoring (ICP) concepts using a low-cost experimental model in a neurointensive care education program. Data concerning ICP monitoring contribute to the patient's clinical assessment and may dictate the course of action of a health team (nursing, medical staff) and influence decisions to determine the appropriate intervention. This study aims to present a safe method for teaching ICP monitoring to medical students in a Simulation Center. Methodology: Medical school teachers, along with students from the 4th year, built an experimental model for teaching ICP measurement. The model consists of a mannequin's head with a plastic bag inside simulating the cerebral ventricle and an inserted ventricular catheter connected to the ICP monitoring system. The bag simulating the ventricle can also be changed for others containing bloody or infected simulated cerebrospinal fluid. On the mannequin's ear, there is a blue point indicating the right place to set the "zero point" for accurate pressure reading. The educational program includes four steps: 1st - Students receive a script on ICP measurement for reading before training; 2nd - Students watch a video about the subject created in the Simulation Center demonstrating each step of the ICP monitoring and the proper care, such as: correct positioning of the patient, anatomical structures to establish the zero point for ICP measurement and a secure range of ICP; 3rd - Students train the procedure in the model. Teachers help students during training; 4th - Student assessment based on a checklist form. Feedback and correction of wrong actions. Results: Students expressed interest in learning ICP monitoring. Tests concerning the hit rate are still being performed. ICP's final results and video will be shown at the event. Conclusion: The study of intracranial pressure measurement based on an experimental model consists of an effective and controlled method of learning and research, more appropriate for teaching neurointensive care practices. Assessment based on a checklist form helps teachers keep track of student learning progress. This project offers medical students a safe method to develop intensive neurological monitoring skills for clinical assessment of patients with neurological disorders.

Keywords: neurology, intracranial pressure, medical education, simulation

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Authors: Marcela De Oliveira, Marina P. Da Silva, Fernando C. G. Da Rocha, Jorge M. Santos, Jaime S. Cardoso, Paulo N. Lisboa-Filho

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Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by neurodegeneration, inflammation, demyelination, and axonal loss. Magnetic resonance imaging (MRI), due to the richness in the information details provided, is the gold standard exam for diagnosis and follow-up of neurodegenerative diseases, such as MS. Brain atrophy, the gradual loss of brain volume, is quite extensive in multiple sclerosis, nearly 0.5-1.35% per year, far off the limits of normal aging. Thus, the brain volume quantification becomes an essential task for future analysis of the occurrence atrophy. The analysis of MRI has become a tedious and complex task for clinicians, who have to manually extract important information. This manual analysis is prone to errors and is time consuming due to various intra- and inter-operator variability. Nowadays, computerized methods for MRI segmentation have been extensively used to assist doctors in quantitative analyzes for disease diagnosis and monitoring. Thus, the purpose of this work was to evaluate the brain volume in MRI of MS patients. We used MRI scans with 30 slices of the five patients diagnosed with multiple sclerosis according to the McDonald criteria. The computational methods for the analysis of images were carried out in two steps: segmentation of the brain and brain volume quantification. The first image processing step was to perform brain extraction by skull stripping from the original image. In the skull stripper for MRI images of the brain, the algorithm registers a grayscale atlas image to the grayscale patient image. The associated brain mask is propagated using the registration transformation. Then this mask is eroded and used for a refined brain extraction based on level-sets (edge of the brain-skull border with dedicated expansion, curvature, and advection terms). In the second step, the brain volume quantification was performed by counting the voxels belonging to the segmentation mask and converted in cc. We observed an average brain volume of 1469.5 cc. We concluded that the automatic method applied in this work can be used for the brain extraction process and brain volume quantification in MRI. The development and use of computer programs can contribute to assist health professionals in the diagnosis and monitoring of patients with neurodegenerative diseases. In future works, we expect to implement more automated methods for the assessment of cerebral atrophy and brain lesions quantification, including machine-learning approaches. Acknowledgements: This work was supported by a grant from Brazilian agency Fundação de Amparo à Pesquisa do Estado de São Paulo (number 2019/16362-5).

Keywords: brain volume, magnetic resonance imaging, multiple sclerosis, skull stripper

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Authors: Nilson Rogério Da Silva, Ingrid Casagrande, Isabela Chicarelli Amaro Santos

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Introduction: People with Autism Spectrum Disorder (ASD) may face difficulties in social inclusion in different segments of society, especially in entering and staying at work. In Brazil, although there is legislation that equates it to the condition of disability, the number of people at work is still low. The United Nations estimates that more than 80 percent of adults with autism are jobless. In Brazil, the scenario is even more nebulous because there is no control and tracking of accurate data on the number of individuals with autism and how many of these are inserted in the labor market. Pereira and Goyos (2019) found that there is practically no scientific production about people with ASD in the labor market. Objective: To describe the experience of people with ASD inserted in the work, facilities and difficulties found in the professional exercise and the strategies used to maintain the job. Methodology: The research was approved by the Research Ethics Committee. As inclusion criteria for participation, the professional should accept to participate voluntarily, be over 18 years of age and have had some experience with the labor market. As exclusion criteria, being under 18 years of age and having never worked in a work activity. Participated in the research of 04 people with a diagnosis of ASD, aged 22 to 32 years. For data collection, an interview script was used that addressed: 1) General characteristics of the participants; 2) Family support; 3) School process; 4) Insertion in the labor market; 5) Exercise of professional activity; (6) Future and Autism; 7) Possible coping strategies. For the analysis of the data obtained, the full transcription of the interviews was performed and the technique of Content Analysis was performed. Results: The participants reported problems in different aspects: In the school environment: difficulty in social relationships, and Bullying. Lack of adaptation to the school curriculum and the structure of the classroom; In the Faculty: difficulty in following the activities, ealizar group work, meeting deadlines and establishing networking; At work: little adaptation in the work environment, difficulty in establishing good professional bonds, difficulty in accepting changes in routine or operational processes, difficulty in understanding veiled social rules. Discussion: The lack of knowledge about what disability is and who the disabled person is leads to misconceptions and negatives regarding their ability to work and in this context, people with disabilities need to constantly prove that they are able to work, study and develop as a human person, which can be classified as ableism. The adaptations and the use of technologies to facilitate the performance of people with ASD, although guaranteed in national legislation, are not always available, highlighting the difficulties and prejudice. Final Considerations: The entry and permanence of people with ASD at work still constitute a challenge to be overcome, involving changes in society in general, in companies, families and government agencies.

Keywords: autism spectrum disorder (ASD), work, disability, autism

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Authors: Mariana Branco, Nahida Sobrino, Cristina Neves, Márcia Santos, Afonso Granja, João Rosa Oliveira, Joana Costa, Luísa Castro Leite

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This case reports a COVID-19 infection in an unvaccinated adult man with no history of COVID-19 and no relevant clinical history besides anabolic steroid use, undergoing weaning with tamoxifen after a bodybuilding competition. The patient presented a 4cm cervical mass 3 weeks after COVID-19 infection in his cohabitants. He was otherwise asymptomatic and tested negative to multiple RT-PCR tests. Nevertheless, the IgG COVID-19 antibody was positive, suggesting the previous infection. This report raises a potential link between anabolic steroid use and atypical COVID-19 onset. Objectives: The goals of this paper are to raise a potential link between anabolic steroid use and atypical COVID-19 onset but also to report an uncommon case of COVID-19 infection with consecutive negative gold standard tests. Methodology: The authors used CARE guidelines for case report writing. Introduction: This case reports a COVID-19 infection case in an unvaccinated adult man, with multiple serial negative reverse transcription polymerase chain reaction (RT-PCR) test results, presenting with single cervical lymphadenopathy. Although the association between COVID-19 and lymphadenopathy is well established, there are no cases with this presentation, and consistently negative RT-PCR tests have been reported. Methodologies: The authors used CARE guidelines for case report writing. Case presentation: This case reports a 28-year-old Caucasian man with no previous history of COVID-19 infection or vaccination and no relevant clinical history besides anabolic steroid use undergoing weaning with tamoxifendue to participation in a bodybuilding competition. He visits his primary care physician because of a large (4 cm) cervical lump, present for 3 days prior to the consultation. There was a positive family history for COVID-19 infection 3 weeks prior to the visit, during which the patient cohabited with the infected family members. The patient never had any previous clinical manifestation of COVID-19 infection and, despite multiple consecutive RT-PCR testing, never tested positive. The patient was treated with an NSAID and a broad-spectrum antibiotic, with little to no effect. Imagiological testing was performed via a cervical ultrasound, followed by a needle biopsy for histologic analysis. Serologic testing for COVID-19 immunity was conducted, revealing a positive Anti-SARS-CoV-2 IgG (Spike S1) antibody, suggesting the previous infection, given the unvaccinated status of our patient Conclusion: In patients with a positive epidemiologic context and cervical lymphadenopathy, physicians should still consider COVID-19 infection as a differential diagnosis, despite negative PCR testing. This case also raises a potential link between anabolic steroid use and atypical COVID-19 onset, never before reported in scientific literature.

Keywords: COVID-19, cervical lymphadenopathy, anabolic steroids, primary care

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Authors: Mareli Fischer, Kevin G. F. Thomas

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Although Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most prevalent childhood neurobehavioural disorders, little empirical research has been published on its clinical presentation in Africa, and, globally, few studies evaluate ADHD intervention programs that emphasize parent training. Hence, Stage 1 of this research programme aimed to describe the functional impairment of South African children with ADHD, and also sought to investigate the influence of sociodemographic variables (e.g., sex, age, socioeconomic status, family environment) and clinical variables (e.g., ADHD subtype and comorbidity) on the degree of that impairment. We used the Mini International Neuropsychiatric Interview for Children and Adolescents as a diagnostic tool, and the Child Behavior Checklist, the Strengths and Difficulties Questionnaire, and the Impairment Rating Scale as measures of functional impairment. Results from this stage of the research indicated that South African children and adolescents who meet diagnostic criteria for ADHD experience most functional impairment in the school domain, as well as in the area of social functioning. None of the measured sociodemographic variables had a significant detrimental or protective effect on how ADHD symptoms impacted on functioning. In terms of comorbidity, the presence of Major Depressive Disorder, Conduct Disorder, and Oppositional Defiant Disorder were all associated with significantly impaired overall functioning. Stage 2 of the research programme aimed to design, implement, and evaluate a child-specific intervention that targeted the primary areas of impairment identified in Stage 1. Existing literature suggests that a positive parent-training programme, in the group format, is one of the best options for cost-effective and successful ADHD intervention. Hence, the intervention took that form. Parents were taught basic behaviour analysis concepts within a supportive group context. Evaluation of the intervention’s efficacy used many of the same measures as in Stage 1, but also featured semi-structured interviews with participants and naturalistic observation of parent-child interaction. We will discuss preliminary results of that evaluation. Studying functional impairment and designing intervention plans in this way will pave the way for evidence-based treatment plans for children and adolescents diagnosed with ADHD.

Keywords: attention deficit/hyperactivity disorder, children, intervention, parenting groups

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Authors: Leonardo Costa Pereira, Frederico Santos Santana, Mauro Karnikowski, Luís Sinésio Silva Neto, Aline Oliveira Gomes, Marisete Peralta Safons, Margô Gomes De Oliveira Karnikowski

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In Brazil, projections of population aging follow all world projections, the birth rate tends to be surpassed by the mortality rate around the year 2045. Historically, the population of Brazilian blacks suffered for several centuries from the oppression of dominant classes. A group, especially of blacks, stands out in relation to territorial, historical and social aspects, and for centuries they have isolated themselves in small communities, in order to maintain their freedom and culture. The isolation of the Quilombola communities generated socioeconomic effects as well as the health of these blacks. Thus, the objective of the present study is to verify the association of body composition parameters with lower and upper limb strength and functional capacity in Quilombola remnants. The research was approved by ethics committee (1,771,159). Anthropometric evaluations of hip and waist circumference, body mass and height were performed. In order to verify the body composition, the relationship between stature and body mass (BM) was performed, generating the body mass index (BMI), as well as the dual-energy X-ray absorptiometry (DEXA) test. The Time Up and Go (TUG) test was used to evaluate the functional capacity, and a maximum repetition test (1MR) for knee extension and handgrip (HG) was applied for strength magnitude analysis. Statistical analysis was performed using the statistical package SPSS 22.0. Shapiro Wilk's normality test was performed. For the possible correlations, the suggestions of the Pearson or Spearman tests were adopted. The results obtained after the interpretation identified that the sample (n = 18) was composed of 66.7% of female individuals with mean age of 66.07 ± 8.95 years. The sample’s body fat percentage (%BF) (35.65 ± 10.73) exceeds the recommendations for age group, as well as the anthropometric parameters of hip (90.91 ± 8.44cm) and waist circumference (80.37 ± 17.5cm). The relationship between height (1.55 ± 0.1m) and body mass (63.44 ± 11.25Kg) generated a BMI of 24.16 ± 7.09Kg/m2, that was considered normal. The TUG performance was 10.71 ± 1.85s. In the 1MR test, 46.67 ± 13.06Kg and in the HG 23.93±7.96Kgf were obtained, respectively. Correlation analyzes were characterized by the high frequency of significant correlations for height, dominant arm mass (DAM), %BF, 1MR and HG variables. In addition, correlations between HG and BM (r = 0.67, p = 0.005), height (r = 0.51, p = 0.004) and DAM (r = 0.55, p = 0.026) were also observed. The strength of the lower limbs correlates with BM (r = 0.69, p = 0.003), height (r = 0.62, p = 0.01) and DAM (r = 0.772, p = 0.001). In this way, we can conclude that not only the simple spatial relationship of mass and height can influence in predictive parameters of strength or functionality, being important the verification of the conditions of the corporal composition. For this population, height seems to be a good predictor of strength and body composition.

Keywords: African Continental Ancestry Group, body composition, functional capacity, strength

Procedia PDF Downloads 275

Authors: Amanda Cristina da Silva Reis, Bruno Paulino Venâncio, Cristina Theada Ferreira, Andrea Fialho do Prado, Lucimara Guedes dos Santos, Aline de Souza Gravatá, Larissa Lima Gonçalves, Isabella Aparecida Ferreira Moretto, João Carlos Ferrari Corrêa, Fernanda Ishida Corrêa

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Objective: To compare two protocols of Transcranial Magnetic Stimulation (TMS) on quadriceps muscle spasticity in individuals diagnosed with Multiple Sclerosis (MS). Method: Clinical, crossover study, in which six adult individuals diagnosed with MS and spasticity in the lower limbs were randomized to receive one session of high-frequency (≥5Hz) and low-frequency (≤ 1Hz) TMS on motor cortex (M1) hotspot for quadriceps muscle, with a one-week interval between the sessions. To assess the spasticity was applied the Ashworth scale and were analyzed the latency time (ms) of the motor evoked potential (MEP) and the central motor conduction time (CMCT) of the bilateral quadriceps muscle. Assessments were performed before and after each intervention. The difference between groups was analyzed using the Friedman test, with a significance level of 0.05 adopted. Results: All statistical analyzes were performed using the SPSS Statistic version 26 programs, with a significance level established for the analyzes at p<0.05. Shapiro Wilk normality test. Parametric data were represented as mean and standard deviation for non-parametric variables, median and interquartile range, and frequency and percentage for categorical variables. There was no clinical change in quadriceps spasticity assessed using the Ashworth scale for the 1 Hz (p=0.813) and 5 Hz (p= 0.232) protocols for both limbs. Motor Evoked Potential latency time: in the 5hz protocol, there was no significant change for the contralateral side from pre to post-treatment (p>0.05), and for the ipsilateral side, there was a decrease in latency time of 0.07 seconds (p<0.05 ); for the 1Hz protocol there was an increase of 0.04 seconds in the latency time (p<0.05) for the contralateral side to the stimulus, and for the ipsilateral side there was a decrease in the latency time of 0.04 seconds (p=<0.05), with a significant difference between the contralateral (p=0.007) and ipsilateral (p=0.014) groups. Central motor conduction time in the 1Hz protocol, there was no change for the contralateral side (p>0.05) and for the ipsilateral side (p>0.05). In the 5Hz protocol for the contralateral side, there was a small decrease in latency time (p<0.05) and for the ipsilateral side, there was a decrease of 0.6 seconds in the latency time (p<0.05) with a significant difference between groups (p=0.019). Conclusion: A high or low-frequency session does not change spasticity, but it is observed that when the low-frequency protocol was performed, there was an increase in latency time on the stimulated side, and a decrease in latency time on the non-stimulated side, considering then that inhibiting the motor cortex increases cortical excitability on the opposite side.

Keywords: multiple sclerosis, spasticity, motor evoked potential, transcranial magnetic stimulation

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Authors: Beatriz Salamanca

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In his public lecture ‘On the American Indians’ given at the University of Salamanca in 1538-39, Francisco de Vitoria presented an unsettling defense of freedom of movement, arguing that the Spanish had the right to travel and dwell in the New World, since it was considered part of the law of nations [ius gentium] that men enjoyed free mutual intercourse anywhere they went. The principle of freedom of movement brought hopeful expectations, promising to bring mankind together and strengthen the ties of fraternity. However, it led to polemical situations when those whose mobility was in question represented a harmful threat or was for some reason undesired. In this context, Vitoria’s argument has been seen on multiple occasions as a justification of the expansion of the Spanish empire. In order to examine the meaning of Vitoria’s defense of free mobility, a more detailed look at Vitoria’s text is required, together with the study of some of his earliest works, among them, his commentaries on Thomas Aquinas’s Summa Theologiae, where he presented relevant insights on the idea of the law of nations. In addition, it is necessary to place Vitoria’s work in the context of the intellectual tradition he belonged to and the responses he obtained from some of his contemporaries who were concerned with similar issues. The claim of this research is that the Spanish right to travel advocated by Vitoria was not intended to be interpreted in absolute terms, for it had to serve the purpose of bringing peace and unity among men, and could not contradict natural law. In addition, Vitoria explicitly observed that the right to travel was only valid if the Spaniards caused no harm, a condition that has been underestimated by his critics. Therefore, Vitoria’s legacy is of enormous value as it initiated a long lasting discussion regarding the question of the grounds under which human mobility could be restricted. Again, under Vitoria’s argument it was clear that this freedom was not absolute, but the controversial nature of his defense of Spanish mobility demonstrates how difficult it was and still is to address the issue of the circulation of peoples across frontiers, and shows the significance of this discussion in today’s globalized world, where the rights and wrongs of notions like immigration, international trade or foreign intervention still lack sufficient consensus. This inquiry about Vitoria’s defense of the principle of freedom of movement is being placed here against the background of the history of political thought, political theory, international law, and international relations, following the methodological framework of contextual history of the ‘Cambridge School’.

Keywords: Francisco de Vitoria, freedom of movement, law of nations, ius gentium, Spanish empire

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Authors: Pedro J. Rolim-Neto, Leslie R. M. Ferraz, Fabiana L. A. Santos, Pablo A. Ferreira, Ricardo T. L. Maia-Jr., Magaly A. M. Lyra, Danilo A F. Fonte, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim

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Initially developed as an antimalarial agent, hydroxychloroquine (HCQ) sulfate is often used as a slow-acting antirheumatic drug in the treatment of disorders of connective tissue. The United States Pharmacopeia (USP) 37 provides a reversed-phase HPLC method for quantification of HCQ. However, this method was not reproducible, producing asymmetric peaks in a long analysis time. The asymmetry of the peak may cause an incorrect calculation of the concentration of the sample. Furthermore, the analysis time is unacceptable, especially regarding the routine of a pharmaceutical industry. The aiming of this study was to develop a fast, easy and efficient method for quantification of HCQ sulfate by High Performance Liquid Chromatography (HPLC) based on the Quality by Design (QbD) methodology. This method was optimized in terms of peak symmetry using the surface area graphic as the Design of Experiments (DoE) and the tailing factor (TF) as an indicator to the Design Space (DS). The reference method used was that described at USP 37 to the quantification of the drug. For the optimized method, was proposed a 33 factorial design, based on the QbD concepts. The DS was created with the TF (in a range between 0.98 and 1.2) in order to demonstrate the ideal analytical conditions. Changes were made in the composition of the USP mobile-phase (USP-MP): USP-MP: Methanol (90:10 v/v, 80:20 v/v and 70:30 v/v), in the flow (0.8, 1.0 and 1.2 mL) and in the oven temperature (30, 35, and 40ºC). The USP method allowed the quantification of drug in a long time (40-50 minutes). In addition, the method uses a high flow rate (1,5 mL.min-1) which increases the consumption of expensive solvents HPLC grade. The main problem observed was the TF value (1,8) that would be accepted if the drug was not a racemic mixture, since the co-elution of the isomers can become an unreliable peak integration. Therefore, the optimization was suggested in order to reduce the analysis time, aiming a better peak resolution and TF. For the optimization method, by the analysis of the surface-response plot it was possible to confirm the ideal setting analytical condition: 45 °C, 0,8 mL.min-1 and 80:20 USP-MP: Methanol. The optimized HPLC method enabled the quantification of HCQ sulfate, with a peak of high resolution, showing a TF value of 1,17. This promotes good co-elution of isomers of the HCQ, ensuring an accurate quantification of the raw material as racemic mixture. This method also proved to be 18 times faster, approximately, compared to the reference method, using a lower flow rate, reducing even more the consumption of the solvents and, consequently, the analysis cost. Thus, an analytical method for the quantification of HCQ sulfate was optimized using QbD methodology. This method proved to be faster and more efficient than the USP method, regarding the retention time and, especially, the peak resolution. The higher resolution in the chromatogram peaks supports the implementation of the method for quantification of the drug as racemic mixture, not requiring the separation of isomers.

Keywords: analytical method, hydroxychloroquine sulfate, quality by design, surface area graphic

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

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Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Amanda Gregorim Fernandes, Lorena Cardoso Cintra, Rosalia Santos Amorim Jesuino, Fabricia Paula De Faria, Marcio José Poças Fonseca

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Bioethanol is one of the most promising biofuels and able to replace fossil fuels and reduce its different environmental impacts and can be generated from various agroindustrial waste. The Brazil is in first place in bioethanol production to be the largest producer of sugarcane. The bagasse sugarcane (SCB) has lignocellulose which is composed of three major components: cellulose, hemicellulose and lignin. Cellulose is a homopolymer of glucose units connected by glycosidic linkages. Among all species of Penicillium, Penicillium echinulatum has been the focus of attention because they produce high quantities of cellulase and the mutant strain 9A02S1 produces higher enzyme levels compared to the wild. Among the cellulases, the cellobiohydrolases enzymes are the main components of the cellulolytic system of fungi, and are also responsible for most of the potential hydrolytic in enzyme cocktails for the industrial processing of plant biomass and several cellobiohydrolases Penicillium had higher specific activity against cellulose compared to CBH I from Trichoderma reesei. This fact makes it an interesting pattern for higher yields in the enzymatic hydrolysis, and also they are important enzymes in the hydrolysis of crystalline regions of cellulose. Therefore, finding new and more active enzymes become necessary. Meanwhile, β-glycosidases act on soluble substrates and are highly dependent on cellobiohydrolases and endoglucanases action to provide the substrate in the hydrolysis of the biomass, but the cellobiohydrolases and endoglucanases are highly dependent β-glucosidases to maintain efficient hydrolysis. Thus, there is a need to understand the structure-function relationships that govern the catalytic activity of cellulolytic enzymes to elucidate its mechanism of action and optimize its potential as industrial biocatalysts. To evaluate the enzyme β-glucosidase of Penicillium echinulatum (PeBGL1) the gene was synthesized from the assembly sequence from a library in induction conditions and then the PeBGL1 gene was cloned in the vector pPICZαA and transformed into P. pastoris GS115. After processing, the producers of PeBGL1 were analyzed for enzyme activity and protein profile where a band of approximately 100 kDa was viewed. It was also carried out the zymogram. In partial characterization it was determined optimum temperature of 50°C and optimum pH of 6,5. In addition, to increase the secreted recombinant PeBGL1 production by Pichia pastoris, three parameters of P. pastoris culture medium were analysed: methanol, nitrogen source concentrations and the inoculum size. A 23 factorial design was effective in achieving the optimum condition. Altogether, these results point to the potential application of this P. echinulatum β-glucosidase in hydrolysis of cellulose for the production of bioethanol.

Keywords: bioethanol, biotechnology, beta-glucosidase, penicillium echinulatum

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Authors: Milton Ixquiac, Erick Montenegro, Francisco Reynoso, Matthew Schmidt, Thomas Mazur, Tianyu Zhao, Hiram Gay, Geoffrey Hugo, Lauren Henke, Jeff Michael Michalski, Angel Velarde, Vicky de Falla, Franky Reyes, Osmar Hernandez, Edgar Aparicio Ruiz, Baozhou Sun

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Purpose: Radiotherapy departments in low- and middle-income countries (LMICs) like Guatemala have recently introduced intensity-modulated radiotherapy (IMRT). IMRT has become the standard of care in high-income countries (HIC) due to reduced toxicity and improved outcomes in some cancers. The purpose of this work is to show the agreement between the dosimetric results shown in the Dose Volume Histograms (DVH) to the objectives proposed in the adopted protocol. This is the initial experience with an O-ring Linac. Methods and Materials: An O-Linac Linac was installed at our clinic in Guatemala in 2019 and has been used to treat approximately 90 patients daily with IMRT. This Linac is a completely Image Guided Device since to deliver each radiotherapy session must take a Mega Voltage Cone Beam Computerized Tomography (MVCBCT). In each MVCBCT, the Linac deliver 9 UM, and they are taken into account while performing the planning. To start the standardization, the TG263 was employed in the nomenclature and adopted a hypofractionated protocol to treat ChestWall, including supraclavicular nodes achieving 40.05Gy in 15 fractions. The planning was developed using 4 semiarcs from 179-305 degrees. The planner must create optimization volumes for targets and Organs at Risk (OARs); the difficulty for the planner was the dose base due to the MVCBCT. To evaluate the planning modality, we used 30 chestwall cases. Results: The plans created manually achieve the protocol objectives. The protocol objectives are the same as the RTOG1005, and the DHV curves look clinically acceptable. Conclusions: Despite the O-ring Linac doesn´t have the capacity to obtain kv images, the cone beam CT was created using MV energy, the dose delivered by the daily image setup process still without affect the dosimetric quality of the plans, and the dose distribution is acceptable achieving the protocol objectives.

Keywords: hypofrationation, VMAT, chestwall, radiotherapy planning

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Authors: Rumeysa Gunduz, Dirk Koester, Thomas Schack

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Previous behavioral studies have shown that working memory (WM) and manual actions share limited capacity cognitive resources, which in turn results in execution costs of manual actions in WM. However, to the best of our knowledge, there is no study investigating the neurophysiology of execution costs. The current study aims to fill this research gap investigating the neurophysiology of execution costs of grasping in WM phases (encoding, maintenance, retrieval) considering verbal and visuospatial domains of WM. A WM-grasping dual task paradigm was implemented to examine execution costs. Baseline single task required performing verbal or visuospatial version of a WM task. Dual task required performing the WM task embedded in a high precision grasp to place task. 30 participants were tested in a 2 (single vs. dual task) x 2 (visuo-spatial vs. verbal WM) within subject design. Event related potentials (ERPs) were extracted for each WM phase separately in the single and dual tasks. Memory performance for visuospatial WM, but not for verbal WM, was significantly lower in the dual task compared to the single task. Encoding related ERPs in the single task revealed different ERPs of verbal WM and visuospatial WM at bilateral anterior sites and right posterior site. In the dual task, bilateral anterior difference disappeared due to bilaterally increased anterior negativities for visuospatial WM. Maintenance related ERPs in the dual task revealed different ERPs of verbal WM and visuospatial WM at bilateral posterior sites. There was also anterior negativity for visuospatial WM. Retrieval related ERPs in the single task revealed different ERPs of verbal WM and visuospatial WM at bilateral posterior sites. In the dual task, there was no difference between verbal WM and visuospatial WM. Behavioral and ERP findings suggest that execution of grasping shares cognitive resources only with visuospatial WM, which in turn results in domain specific execution costs. Moreover, ERP findings suggest unique patterns of costs in each WM phase, which supports the idea that each WM phase reflects a separate cognitive process. This study not only contributes to the understanding of cognitive principles of manual action control, but also contributes to the understanding of WM as an entity consisting of separate modalities and cognitive processes.

Keywords: dual task, grasping execution, neurophysiology, working memory domains, working memory phases

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Authors: Thomas Arink, Isam Janajreh

Abstract:

The petroleum industry generates significant amounts of waste in the form of drill cuttings, contaminated soil and oily sludge. Drill cuttings are a product of the off-shore drilling rigs, containing wet soil and total petroleum hydrocarbons (TPH). Contaminated soil comes from different on-shore sites and also contains TPH. The oily sludge is mainly residue or tank bottom sludge from storage tanks. The two main treatment methods currently used are incineration and thermal desorption (TD). Thermal desorption is a method where the waste material is heated to 450ºC in an anaerobic environment to release volatiles, the condensed volatiles can be used as a liquid fuel. For the thermal desorption unit dry contaminated soil is mixed with moist drill cuttings to generate a suitable mixture. By thermo gravimetric analysis (TGA) of the TD feedstock it was found that less than 50% of the TPH are released, the discharged material is stored in landfill. This study proposes co-gasification of petroleum waste with waste tires as an alternative to thermal desorption. Co-gasification with a high-calorific material is necessary since the petroleum waste consists of more than 60 wt% ash (soil/sand), causing its calorific value to be too low for gasification. Since the gasification process occurs at 900ºC and higher, close to 100% of the TPH can be released, according to the TGA. This work consists of three parts: 1. a mathematical gasification model, 2. a reactive flow CFD model and 3. experimental work on a drop tube reactor. Extensive material characterization was done by means of proximate analysis (TGA), ultimate analysis (CHNOS flash analysis) and calorific value measurements (Bomb calorimeter) for the input parameters of the mathematical and CFD model. The mathematical model is a zero dimensional model based on Gibbs energy minimization together with Lagrange multiplier; it is used to find the product species composition (molar fractions of CO, H2, CH4 etc.) for different tire/petroleum feedstock mixtures and equivalence ratios. The results of the mathematical model act as a reference for the CFD model of the drop-tube reactor. With the CFD model the efficiency and product species composition can be predicted for different mixtures and particle sizes. Finally both models are verified by experiments on a drop tube reactor (1540 mm long, 66 mm inner diameter, 1400 K maximum temperature).

Keywords: computational fluid dynamics (CFD), drop tube reactor, gasification, Gibbs energy minimization, petroleum waste, waste tires

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Authors: Oris Tom-Lawyer, Michael Thomas

Abstract:

This paper seeks to analyse the hegemony of the English language in Western Africa through the lens of educational policies and the socio-economic functions of the language. It is based on the premise that there is a positive link between the English language and development contexts. The study aims to fill a gap in the research literature by examining the usefulness of hegemony as a concept to explain the role of English language in the region, thus countering the negative connotations that often accompany it. The study identified four main research questions: i. What are the socio-economic functions of English in Francophone/lusophone countries? ii. What factors promote the hegemony of English in anglophone countries? iii. To what extent is the hegemony of English in West Africa? iv. What are the implications of the non-hegemony of English in Western Africa? Based on a meta-analysis of the research literature between 2003 and 2018, the findings of the study revealed that in francophone/lusophone countries, English functions in the following socio-economic domains; they are peace keeping missions, regional organisations, commercial and industrial sectors, as an unofficial international language and as a foreign language. The factors that promote linguistic hegemony of English in anglophone countries are English as an official language, a medium of instruction, lingua franca, cultural language, language of politics, language of commerce, channel of development and English for media and entertainment. In addition, the extent of the hegemony of English in West Africa can be viewed from the factors that contribute to the non-hegemony of English in the region; they are French language, Portuguese language, the French culture, neo-colonialism, level of poverty, and economic ties of French to its former colonies. Finally, the implications of the non-hegemony of English language in West Africa are industrial backwardness, poverty rate, lack of social mobility, drop out of school rate, growing interest in English, access to limited internet information and lack of extensive career opportunities. The paper concludes that the hegemony of English has resulted in the development of anglophone countries in Western Africa, while in the francophone/lusophone regions of the continent, industrial backwardness and low literacy rates have been consequences of English language marginalisation. In conclusion, the paper makes several recommendations, including the need for the early introduction of English into French curricula as part of a potential solution.

Keywords: developmental tool, English language, linguistic hegemony, West Africa

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Authors: Tarek K. Jalouta, Jolietta R. Holliman, Kathryn R. Burke, Kathleen M. Bewley-Thomas

Abstract:

Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. In the United States, HCV screening awareness, treatment, and linkage to care are under continues ascending progress. However, still millions of people are asymptomatically infected and undiagnosed yet. Through this community mission, we sought to identify the best and the newest strategies to identify those infected people to educate them, link them to care and cure them. Methods: We have identified patients that did not have a prior HCV screening in our Electronic medical record (EMR) including all our different hospital locations (South Suburban Chicago, Northern, Western and Central Indiana). Providing education to all Primary care/Gastroenterology/Infectious diseases providers and staff in the clinic to increase awareness of the HCV screening. Health-related quality of life, chronic clinical complications, and demographics data were collected for each patient. All outcomes of HCV antibody-reactive and HCV RNA–positive results were identified and statistically analyzed. Results: From July 2016 to July 2018 we screened 35,720 individuals of birth cohort in our different Franciscan’s health medical centers. Of the screened population, 986 (2.7%) individuals were HCV AB-reactive. Of those, 319 (1%) patients were HCV RNA-positive, and 264 patients were counseled and linked to providers. 34 patients initiated anti-HCV therapy with successful treatment. Conclusions: Our HCV screening augmentation project considered the largest screening program in the Midwest. Augmenting the HCV screening process through creating a Best Practice Alert (BPA) in the EMR (Epic Sys.) and point of care testing could be helpful. Although continued work is required, our team is working on increase screening through adding HCV test to CBC-Panels in Emergency Department settings, phone calls to all birth cohort individuals through Robo-Calling System aimed to reach 75,000 individuals by 2019. However, a better linkage to care and referral monitoring system to all HCV RNA positive patients is still needed, and access to therapy, especially for uninsured patients, is challenging.

Keywords: chronic hepatitis C, chronic hepatitis C treatment, chronic hepatitis C screening, chronic hepatitis C prevention, liver cancer

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