Search results for: clinical prediction score

Authors: Daniel Tscharnuter, Eliza Truszkiewicz, Gerald Pinter

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High-quality surfaces of plastic parts can be achieved in a very cost-effective manner using in-mold processes, where e.g. scratch resistant or high gloss polymer films are pre-formed and subsequently receive their support structure by injection molding. The pre-forming may be done by high-pressure forming. In this process, a polymer sheet is heated and subsequently formed into the mold by pressurized air. Due to the heat transfer to the cooled mold the polymer temperature drops below its glass transition temperature. This ensures that the deformed microstructure is retained after depressurizing, giving the sheet its final formed shape. The development of a forming process relies heavily on the experience of engineers and trial-and-error procedures. Repeated mold design and testing cycles are however both time- and cost-intensive. It is, therefore, desirable to study the process using reliable computer simulations. Through simulations, the construction of the mold and the effect of various process parameters, e.g. temperature levels, non-uniform heating or timing and magnitude of pressure, on the deformation of the polymer sheet can be analyzed. Detailed knowledge of the deformation is particularly important in the forming of polymer films with integrated electro-optical functions. Care must be taken in the placement of devices, sensors and electrical and optical paths, which are far more sensitive to deformation than the polymers. Reliable numerical prediction of the deformation of the polymer sheets requires sophisticated material models. Polymer films are often either transversely isotropic or orthotropic due to molecular orientations induced during manufacturing. The anisotropic behavior affects the resulting strain field in the deformed film. For example, parts of the same shape but different strain fields may be created by varying the orientation of the film with respect to the mold. The numerical simulation of the high-pressure forming of such films thus requires material models that can capture the nonlinear anisotropic mechanical behavior. There are numerous commercial polymer grades for the engineers to choose from when developing a new part. The effort required for comprehensive material characterization may be prohibitive, especially when several materials are candidates for a specific application. We, therefore, propose a class of models for compressible hyperelasticity, which may be determined from basic experimental data and which can capture key features of the mechanical response. Invariant-based hyperelastic models with a reduced number of invariants are formulated in a semi-numerical way, such that the models are determined from a single uniaxial tensile tests for isotropic materials, or two tensile tests in the principal directions for transversely isotropic or orthotropic materials. The simulation of the high pressure forming of an orthotropic polymer film is finally done using an orthotropic formulation of the hyperelastic model.

Keywords: hyperelastic, anisotropic, polymer film, thermoforming

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Authors: L. Beltran, S. Solano, T. Lacruz, M. Blanco, M. Rojo, M. Graell, A. R. Sepulveda

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Introduction and Objective: Given the difficulties of assessing Binge Eating Disorder during childhood, episodes of Loss of Control (LOC) eating can be a key symptom. The objective is to know the prevalence of food psychopathology depending on the type of evaluation and find out which psychological characteristics differentiate overweight or obese children who present LOC from those who do not. Material and Methods: 170 children from 8 to 12 years of age with overweight or obesity (P > 85) were evaluated through the Primary Care Centers of Madrid. Sociodemographic data and psychological measures were collected through the Kiddie-Schedule for Affective Disorders & Schizophrenia, Present & Lifetime Version (K-SADS-PL) diagnostic interview and self-applied questionnaires: Children's eating attitudes (ChEAT), depressive symptomatology (CDI), anxiety (STAIC), general self-esteem (LAWSEQ), body self-esteem (BES), perceived teasing (POTS) and perfectionism (CAPS). Results: 15.2% of the sample exceeded the ChEAT cut-off point, presenting a risk of pathological eating; 5.88% presented an Eating Disorder through the diagnostic interview (2.35% Binge Eating disorder), and 33.53% had LOC episodes. No relationship was found between the presence of LOC and clinical diagnosis of eating disorders according to DSM-V; however, the group with LOC presented a higher risk of eating psychopathology using the ChEAT (p < .02). Significant differences were found in the group with LOC (p < .02): higher z-BMI, lower body self-esteem, greater anxious symptomatology, greater frequency of teasing towards weight, and greater effect of teasing both towards weight and competitions; compared to their peers without LOC. Conclusion: According to previous studies in samples with overweight children, in this Spanish sample of children with obesity, we found a prevalence of moderate eating disorder and a high presence of LOC episodes, which is related to both eating and general psychopathology. These findings confirm that the exclusion of LOC episodes as a diagnostic criterion can underestimate the presence of eating psychopathology during this developmental stage. According to these results, it is highly recommended to promote school context programs that approach LOC episodes in order to reduce associated symptoms. This study is included in a Project funded by the Ministry of Innovation and Science (PSI2011-23127).

Keywords: childhood obesity, eating psychopathology, loss-of-control eating, psychological symptomatology

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Authors: Lucie Matricon, Anne Roubaud, Geert Haarlemmer, Christophe Geantet

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Introduction: This case discusses the management of two floor of mouth (FOM) Squamous Cell Carcinomas (SCC) not identified upon initial biopsy. Case Report: A 51 year-old male presented with right FOM erythroleukoplakia. Relevant medical history included alcoholic dependence syndrome and alcoholic liver disease. Relevant drug therapy encompassed acamprosate, folic acid, hydroxocobalamin and thiamine. The patient had a 55.5 pack-year smoking history and alcohol dependence from age 14, drinking 16 units/day. FOM incisional biopsy and histopathological analysis diagnosed Carcinoma in situ. Treatment involved wide local excision. Specimen analysis revealed two separate foci of pT1 moderately differentiated SCCs. Carcinoma staging scans revealed no pathological lymphadenopathy, no local invasion or metastasis. SCCs had been excised in completion with narrow margins. MDT discussion concluded that in view of the field changes it would be difficult to identify specific areas needing further excision, although techniques such as Lugol’s Iodine were considered. Further surgical resection, surgical neck management and sentinel lymph node biopsy was offered. The patient declined intervention, primary management involved close monitoring alongside alcohol and smoking cessation referral. Discussion: Narrow excisional margins can increase carcinoma recurrence risk. Biopsy failed to identify SCCs, despite sampling an area of clinical concern. For gross field change multiple incisional biopsies should be considered to increase chance of accurate diagnosis and appropriate treatment. Coupling of tobacco and alcohol has a synergistic effect, exponentially increasing the relative risk of oral carcinoma development. Tobacco and alcoholic control is fundamental in reducing treatment‑related side effects, recurrence risk, and second primary cancer development.

Keywords: microalgae, biofuels, hydrothermal liquefaction, biomass

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Authors: Chen Wang, Jared Evans, Yan Asmann

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With the quick evolvement of next-generation sequencing techniques, whole-exome or exome-panel data have become a cost-effective way for detection of small exonic mutations, but there has been a growing desire to accurately detect copy number variations (CNVs) as well. In order to address this research and clinical needs, we developed a sequencing coverage pattern-based method not only for copy number detections, data integrity checks, CNV calling, and visualization reports. The developed methodologies include complete automation to increase usability, genome content-coverage bias correction, CNV segmentation, data quality reports, and publication quality images. Automatic identification and removal of poor quality outlier samples were made automatically. Multiple experimental batches were routinely detected and further reduced for a clean subset of samples before analysis. Algorithm improvements were also made to improve somatic CNV detection as well as germline CNV detection in trio family. Additionally, a set of utilities was included to facilitate users for producing CNV plots in focused genes of interest. We demonstrate the somatic CNV enhancements by accurately detecting CNVs in whole exome-wide data from the cancer genome atlas cancer samples and a lymphoma case study with paired tumor and normal samples. We also showed our efficient reuses of existing exome sequencing data, for improved germline CNV calling in a family of the trio from the phase-III study of 1000 Genome to detect CNVs with various modes of inheritance. The performance of the developed method is evaluated by comparing CNV calling results with results from other orthogonal copy number platforms. Through our case studies, reuses of exome sequencing data for calling CNVs have several noticeable functionalities, including a better quality control for exome sequencing data, improved joint analysis with single nucleotide variant calls, and novel genomic discovery of under-utilized existing whole exome and custom exome panel data.

Keywords: bioinformatics, computational genetics, copy number variations, data reuse, exome sequencing, next generation sequencing

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Authors: Thanooja Naushad, Meena Natarajan, Tushar Vasant Kulkarni

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Background: The Lacey Assessment of Preterm Infants (LAPI) is used in clinical practice to identify premature babies at risk of neuromotor impairments, especially cerebral palsy. This study attempted to find the validity of the Lacey assessment of preterm infants to predict neuromotor outcomes of premature babies at 12 months corrected age and to compare its predictive ability with the brain ultrasound. Methods: This prospective cohort study included 89 preterm infants (45 females and 44 males) born below 35 weeks gestation who were admitted to the neonatal intensive care unit of a government hospital in Dubai. Initial assessment was done using the Lacey assessment after the babies reached 33 weeks postmenstrual age. Follow up assessment on neuromotor outcomes was done at 12 months (± 1 week) corrected age using two standardized outcome measures, i.e., infant neurological international battery and Alberta infant motor scale. Brain ultrasound data were collected retrospectively. Data were statistically analyzed, and the diagnostic accuracy of the Lacey assessment of preterm infants (LAPI) was calculated -when used alone and in combination with the brain ultrasound. Results: On comparison with brain ultrasound, the Lacey assessment showed superior specificity (96% vs. 77%), higher positive predictive value (57% vs. 22%), and higher positive likelihood ratio (18 vs. 3) to predict neuromotor outcomes at one year of age. The sensitivity of Lacey assessment was lower than brain ultrasound (66% vs. 83%), whereas specificity was similar (97% vs. 98%). A combination of Lacey assessment and brain ultrasound results showed higher sensitivity (80%), positive (66%), and negative (98%) predictive values, positive likelihood ratio (24), and test accuracy (95%) than Lacey assessment alone in predicting neurological outcomes. The negative predictive value of the Lacey assessment was similar to that of its combination with brain ultrasound (96%). Conclusion: Results of this study suggest that the Lacey assessment of preterm infants can be used as a supplementary assessment tool for premature babies in the neonatal intensive care unit. Due to its high specificity, Lacey assessment can be used to identify those babies at low risk of abnormal neuromotor outcomes at a later age. When used along with the findings of the brain ultrasound, Lacey assessment has better sensitivity to identify preterm babies at particular risk. These findings have applications in identifying premature babies who may benefit from early intervention services.

Keywords: brain ultrasound, lacey assessment of preterm infants, neuromotor outcomes, preterm

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Authors: Mami Miyasaka, Kaichi Yanaoka

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Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity; symptoms often manifest during childhood. In children with ADHD, the development of inhibitory processes is impaired. Inhibitory control allows people to avoid processing unnecessary stimuli and to behave appropriately in various situations; thus, people with ADHD require interventions to improve inhibitory control. Positive or negative reinforcements (i.e., reward or punishment) help improve the performance of children with such difficulties. However, in order to optimize impact, reward and punishment must be presented immediately following the relevant behavior. In regular elementary school classrooms, such supports are uncommon; hence, an alternative practical intervention method is required. One potential intervention involves setting goals to keep children motivated to perform tasks. This study examined whether goal setting improved inhibitory performances, especially for children with severe ADHD-related symptoms. We also focused on giving feedback on children's task performances. We expected that giving children feedback would help them set reasonable goals and monitor their performance. Feedback can be especially effective for children with severe ADHD-related symptoms because they have difficulty monitoring their own performance, perceiving their errors, and correcting their behavior. Our prediction was that goal setting by itself would be effective for children with mild ADHD-related symptoms, and goal setting based on feedback would be effective for children with severe ADHD-related symptoms. Japanese elementary school children and their parents were the sample for this study. Children performed two kinds of go/no-go tasks, and parents completed a checklist about their children's ADHD symptoms, the ADHD Rating Scale-IV, and the Conners 3rd edition. The go/no-go task is a cognitive task to measure inhibitory performance. Children were asked to press a key on the keyboard when a particular symbol appeared on the screen (go stimulus) and to refrain from doing so when another symbol was displayed (no-go stimulus). Errors obtained in response to a no-go stimulus indicated inhibitory impairment. To examine the effect of goal-setting on inhibitory control, 37 children (Mage = 9.49 ± 0.51) were required to set a performance goal, and 34 children (Mage = 9.44 ± 0.50) were not. Further, to manipulate the presence of feedback, in one go/no-go task, no information about children’s scores was provided; however, scores were revealed for the other type of go/no-go tasks. The results revealed a significant interaction between goal setting and feedback. However, three-way interaction between ADHD-related inattention, feedback, and goal setting was not significant. These results indicated that goal setting was effective for improving the performance of the go/no-go task only with feedback, regardless of ADHD severity. Furthermore, we found an interaction between ADHD-related inattention and feedback, indicating that informing inattentive children of their scores made them unexpectedly more impulsive. Taken together, giving feedback was, unexpectedly, too demanding for children with severe ADHD-related symptoms, but the combination of goal setting with feedback was effective for improving their inhibitory control. We discuss effective interventions for children with ADHD from the perspective of goal setting and feedback. This work was supported by the 14th Hakuho Research Grant for Child Education of the Hakuho Foundation.

Keywords: attention deficit disorder with hyperactivity, feedback, goal-setting, go/no-go task, inhibitory control

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Authors: Vrinda Hari Ankolekar, Anne D. Souza, Mamatha Hosapatna

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Introduction: Precise anatomical assessment of femoral neck anteversion (FNA) and the neck shaft angles (NSA) would be essential in diagnosing the pathological conditions involving hip joint and its ligaments. FNA of greater than 20 degrees is considered excessive femoral anteversion, whereas a torsion angle of fewer than 10 degrees is considered femoral retroversion. Excessive femoral torsion is not uncommon and has been associated with certain neurologic and orthopedic conditions. The enlargement and maturation of the hip joint increases at the 20th week of gestation and the NSA ranges from 135- 140◦ at birth. Material and methods: 48 femurs were tagged according to the GA and two photographs for each femur were taken using Nikon digital camera. Each femur was kept on a horizontal hard desk and end on an image of the upper end was taken for the estimation of FNA and a photograph in a perpendicular plane was taken to calculate the NSA. The images were transferred to the computer and were stored in TIFF format. Microsoft Paint software was used to mark the points and Image J software was used to calculate the angles digitally. 1. Calculation of FNA: The midpoint of the femoral head and the neck were marked and a line was drawn joining these two points. The angle made by this line with the horizontal plane was measured as FNA. 2. Calculation of NSA: The midpoint of the femoral head and the neck were marked and a line was drawn joining these two points. A vertical line was drawn passing through the tip of the greater trochanter to the inter-condylar notch. The angle formed by these lines was calculated as NSA. Results: The paired t-test for the inter-observer variability showed no significant difference between the values of two observers. (FNA: t=-1.06 and p=0.31; NSA: t=-0.09 and p=0.9). The FNA ranged from 17.08º to 33.97 º on right and 17.32 º to 45.08 º on left. The NSA ranged from 139.33 º to 124.91 º on right and 143.98 º to 123.8 º on left. Unpaired t-test was applied to compare the mean angles between the second and third trimesters which did not show any statistical significance. This shows that the FNA and NSA of femur did not vary significantly during the third trimester. The FNA and NSA were correlated with the GA using Pearson’s correlation. FNA appeared to increase with the GA (r=0.5) but the increase was not statistically significant. A decrease in the NSA was also noted with the GA (r=-0.3) which was also statistically not significant. Conclusion: The present study evaluates the FNA and NSA of the femur in fetuses and correlates their development with the GA during second and third trimesters. The FNA and NSA did not vary significantly during the third trimester.

Keywords: anteversion, coxa antetorsa, femoral torsion, femur neck shaft angle

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Authors: Getahun Nigusie Demise

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Background; antiretroviral treatment reduce HIV-related morbidity, and prolonged survival of patients however, there is lack of up-to-date information concerning the treatment long term effect on the survival of HIV positive children especially in the study area. Objective: The aim of this study is to assess the incidence and predictors of mortality among HIV positive children on antiretroviral therapy (ART) in public hospitals of Harer town who were enrolled from 2011 to 2021. Methodology: Institution based retrospective cohort study was conducted among 429 HIV positive children enrolled in ART clinic from January 1st 2011 to December30th 2021. Data were collected from medical cards by using a data extraction form, Descriptive analyses were used to Summarized the results, and life table was used to estimate survival probability at specific point of time after introduction of ART. Kaplan Meier survival curve together with log rank test was used to compare survival between different categories of covariates, and Multivariate Cox-proportional hazard regression model was used to estimate adjusted Hazard rate. Variables with p-values ≤0.25 in bivariable analysis were candidates to the multivariable analysis. Finally, variables with p-values < 0.05 were considered as significant variables. Results: The study participants had followed for a total of 2549.6 child-years (30596 child months) with an overall mortality rate of 1.5 (95% CI: 1.1, 2.04) per 100 child-years. Their median survival time was 112 months (95% CI: 101–117). There were 38 children with unknown outcome, 39 deaths, and 55 children transfer out to different facility. The overall survival at 6, 12, 24, 48 months were 98%, 96%, 95%, 94% respectively. being in WHO clinical Stage four (AHR=4.55, 95% CI:1.36, 15.24), having anemia(AHR=2.56, 95% CI:1.11, 5.93), baseline low absolute CD4 count (AHR=2.95, 95% CI: 1.22, 7.12), stunting (AHR=4.1, 95% CI: 1.11, 15.42), wasting (AHR=4.93, 95% CI: 1.31, 18.76), poor adherence to treatment (AHR=3.37, 95% CI: 1.25, 9.11), having TB infection at enrollment (AHR=3.26, 95% CI: 1.25, 8.49),and no history of change their regimen(AHR=7.1, 95% CI: 2.74, 18.24), were independent predictors of death. Conclusion: more than half of death occurs within 2 years. Prevalent tuberculosis, anemia, wasting, and stunting nutritional status, socioeconomic factors, and baseline opportunistic infection were independent predictors of death. Increasing early screening and managing those predictors are required.

Keywords: human immunodeficiency virus-positive children, anti-retroviral therapy, survival, treatment, Ethiopia

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Authors: Mazoun Nasser Rashid Al Kharusi, Nada Al Siyabi

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Objectives: The main aim of this study is to Find the rate of susceptibility of ESBL E. coli causing UTI to oral antibiotics. Secondary objectives: Prevalence of ESBL E. coli from community urine samples, identify the best empirical oral antibiotics with the least resistance rate for UTI and identify alternative oral antibiotics for testing and utilization. Methods: This study is a retrospective descriptive study of the last three years in five major hospitals in Oman (Khowla Hospital, AN’Nahdha Hospital, Rustaq Hospital, Nizwa Hospital, and Ibri Hospital) equipped with a microbiologist. Inclusion criteria include all eligible outpatient urine culture isolates, excluding isolates from admitted patients with hospital-acquired urinary tract infections. Data was collected through the MOH database. The MOH hospitals are using different types of testing, automated methods like Vitek2 and manual methods. Vitek2 machine uses the principle of the fluorogenic method for organism identification and a turbidimetric method for susceptibility testing. The manual method is done by double disc diffusion for identifying ESBL and the disc diffusion method is for antibiotic susceptibility. All laboratories follow the clinical laboratory science institute (CLSI) guidelines. Analysis was done by SPSS statistical package. Results: Total urine cultures were (23048). E. coli grew in (11637) 49.6% of the urine, whereas (2199) 18.8% of those were confirmed as ESBL. As expected, the resistance rate to amoxicillin and cefuroxime is 100%. Moreover, the susceptibility of those ESBL-producing E. coli to nitrofurantoin, trimethoprim+sulfamethoxazole, ciprofloxacin and amoxicillin-clavulanate is progressing over the years; however, still low. ESBL E. coli was predominating in the female gender and those aged 66-74 years old throughout all the years. Other oral antibiotic options need to be explored and tested so that we add to the pool of oral antibiotics for ESBL E. coli causing UTI in the community. Conclusion: High rate of ESBL E. coli in urine from the community. The high resistance rates to oral antibiotics highlight the need for alternative treatment options for UTIs caused by these bacteria. Further research is needed to identify new and effective treatments for UTIs caused by ESBL-E. Coli.

Keywords: UTI, ESBL, oral antibiotics, E. coli, susceptibility

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Authors: Dina Siniora, Jasia Baig

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During the past few decades, the healthcare system has undergone profound changes in their healthcare decision-making competencies and moral aptitudes due to the vast advancement in technology, clinical skills, and scientific knowledge. Healthcare decision-making deals with morally contentious dilemmas ranging from illness, life and death judgments that require sensitivity and awareness towards the patient’s preferences while taking into consideration medicine’s abilities and boundaries. As the ever-evolving field of medicine continues to become more scientifically and morally multifarious; physicians and the hospital administrators increasingly rely on ethics committees to resolve problems that arise in everyday patient care. The role and latitude of responsibilities of ethics committees which includes being dispute intermediaries, moral analysts, policy educators, counselors, advocates, and reviewers; suggest the importance and effectiveness of a fully integrated committee. Despite achievements on Integrated Ethics and progress in standards and competencies, there is an imminent necessity for further improvement in quality within ethics consultation services in areas of credentialing, professionalism and standards of quality, as well as the quality of healthcare throughout the system. These concerns can be resolved first by collecting data about particular quality gaps and comprehend the level to which ethics committees are consistent with newly published ASBH quality standards. Policymakers should pursue improvement strategies that target both academic bioethics community and major stakeholders at hospitals, who directly influence ethics committees. This broader approach oriented towards education and intervention outcome in conjunction with preventive ethics to address disparities in quality on a systematic level. Adopting tools for improving competencies and processes within ethics consultation by implementing a credentialing process, upholding normative significance for the ASBH core competencies, advocating for professional Code of Ethics, and further clarifying the internal structures will improve productivity, patient satisfaction, and institutional integrity. This cannot be systemically achieved without a written certification exam for HCEC practitioners, credentialing and privileging HCEC practitioners at the hospital level, and accrediting HCEC services at the institutional level.

Keywords: ethics consultation, hospital, medical ethics, quality

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Authors: Lakshmi Sujeesh, Aaron Ramzeen, Ricky Ziming Guo, Abhishek Agrawal

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Introduction: Range of motion (ROM) is often measured by physiotherapists using hand-held goniometer as part of mobility assessment for diagnosis. Due to the nature of hand-held goniometer measurement procedure, readings often tend to have some variations depending on the physical therapist taking the measurements (Riddle et al.). This study aims to validate computer vision software readings against goniometric measurements for quick and consistent ROM measurements to be taken by clinicians. The use of this computer vision software hopes to improve the future of musculoskeletal space with more efficient diagnosis from recording of patient’s ROM with minimal human error across different physical therapists. Methods: Using the hand-held long arm goniometer measurements as the “gold-standard”, healthy study participants (n = 20) were made to perform 4 exercises: Front elevation, Abduction, Internal Rotation, and External Rotation, using both arms. Assessment of active ROM using computer vision software at different angles set by goniometer for each exercise was done. Interclass Correlation Coefficient (ICC) using 2-way random effects model, Box-Whisker plots, and Root Mean Square error (RMSE) were used to find the degree of correlation and absolute error measured between set and recorded angles across the repeated trials by the same rater. Results: ICC (2,1) values for all 4 exercises are above 0.9, indicating excellent reliability. Lowest overall RMSE was for external rotation (5.67°) and highest for front elevation (8.00°). Box-whisker plots showed have showed that there is a potential zero error in the measurements done by the computer vision software for abduction, where absolute error for measurements taken at 0 degree are shifted away from the ideal 0 line, with its lowest recorded error being 8°. Conclusion: Our results indicate that the use of computer vision software is valid and reliable to use in clinical settings by physiotherapists for measuring shoulder ROM. Overall, computer vision helps improve accessibility to quality care provided for individual patients, with the ability to assess ROM for their condition at home throughout a full cycle of musculoskeletal care (American Academy of Orthopaedic Surgeons) without the need for a trained therapist.

Keywords: physiotherapy, frozen shoulder, joint range of motion, computer vision

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Authors: O. O. Oku, K. S. Jerry-Alagbaoso

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It is universally acknowledged that the primary function of universities is the generation and dissemination of knowledge. This mission is pursued through the research component of the university programme especially at the post-graduate level. The senior academic staff teach, supervise and provide general academic leadership to post-graduate students who are expected to carry out research leading to the presentation of dissertation as requirement for the award of doctoral degree in their various disciplines. Carrying out the research enterprises involves a lot of corroboration among individuals and communities. The need to safeguard the interest of everyone involved in the enterprise makes the development of ethical standard in research imperative. Ensuring the development and effective application of such ethical standard falls within the leadership role of the vice –chancellors, Deans of post-graduate schools/ faculties, Heads of Departments and supervisors. It is the relevance and application of such ethical standard in Nigerian university research efforts that this study discussed. The study adopted the descriptive research design. A researcher-made 4 point rating scale was used to elicit information from the post-graduate dissertation supervisors sampled from one university each from the six geo-political zones in Nigeria using the purposive sampling technique. The data collected was analysed using the mean score and standard deviation. The findings of the study include among others that there are several cases of unethical practices by Ph.D dissertation students in Nigerian universities. Prominent among these include duplicating research topics, making unauthorized copies of data paper or computer programme, failing to acknowledge contributions of relevant people and authors, rigging an experiment to prempt the result among others. Some of the causes of the unethical practices according to the respondents include inadequate funding of universities resulting in inadequate remuneration for university teachers, inadequacy of equipment and infrastructures, poor supervision of Ph.D students,’ poverty on the side of the student researchers and non-application of sanctions on violators. Improved funding of the Nigerian universities system with emphasis on both staff and student research efforts, admitting academic oriented students into the Ph.D programme and ensuring the application of appropriate sanctions in cases of unethical conduct in research featured prominently in the needed leadership imperatives. Based on the findings of the study, the researchers recommend the development of university research policies that is closely tied to each university’s strategic plan. Such plan should explain the research focus that will attract more funding and direct students interest towards it without violating the principle of academic freedom. The plan should also incorporate the establishment of a research administration office to provide the necessary link between the students and funding agencies and also organise training for supervisors on leadership activities expected of them while educating students on the processes involved in carrying out a qualitative and acceptable research study. Such exercise should include the ethical principles and guidelines that comprise all parts of research from research topic through the literature review to the design and the truthful reporting of results.

Keywords: academic leadership, ethical standards, research stakeholders, research enterprise

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Authors: Anna Tokajuk, Agnieszka Zakrzeska, Ewa Chabielska, Halina Car

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Whey is a by-product generated mainly in the production of cheese and casein. Powder forms of whey are used widely in the food industry as well as a high-protein food for infants, for convalescents, by athletes and especially by bodybuilders to increase muscle mass during exercise. Whey protein concentrate-80 (WPC-80) is a source of bioactive peptides with beneficial effects on the cardiovascular system. It is known that whey proteins health beneficial properties include antidiabetic, blood pressure lowering, improving cardiovascular system function, antibacterial, antiviral and other effects. To study its influence on the development of thrombosis, venous thrombosis model was performed according to the protocol featured by Reyers with modification by Chabielska and Gromotowicz. Male Wistar-Crl: WI (Han) rats from researched groups were supplemented with two doses of WPC-80 (0.3 or 0.5 g/kg) for 7, 14 or 21 days and after these periods, one-hour venous thrombosis model was performed. Control group received 0.9 % NaCl solution and was sham operated. The statistical significance of results was computed by Mann – Whitney’s test. We observed that thrombus weight was decreased in animals obtaining WPC-8080 and that was statistically significant in 14 and 21-day supplemented groups. Blood count parameters did not differ significantly in rats with and without thrombosis induction whether they were fed with WPC-80 or not. Moreover, the number of platelets (PLT) was within the normal range in each group. The examined coagulation parameters in rats of the control groups were within normal limits. After WPC-80 supplementation there was the tendency to prolonged activated partial thromboplastin time (aPTT), but in comparison, the results did not turn out significant. In animals that received WPC-80 0.3 g·kg-1 for 21 days with and without induced thrombosis, prothrombin time (PT) and an international normalized ratio (INR) was somewhat decreased, remaining within the normal range, but the nature and significance of this observation are beyond the framework of the current study. Additionally, fibrinogen and thrombin time (TT) did not differ significantly between groups. Therefore the exact effect of WPC-80 on coagulation system is still elusive and requires further thorough research including mechanisms of action. Determining the potential clinical application of WPC-80 requires the selection of the optimal dose and duration of supplementation.

Keywords: antithrombotic, rats, venous thrombosis, WPC-80

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Authors: Mmamapudi Kubjane, Natacha Berkowitz, Rene Goliath, Naomi S. Levitt, Robert J. Wilkinson, Tolu Oni

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Background: South Africa remains a high tuberculosis (TB) burden country globally and the burden of diabetes – a TB risk factor is growing rapidly. As an infectious disease, TB also induces transient hyperglycaemia. Therefore, screening for diabetes in newly diagnosed tuberculosis patients may result in misclassification of transient hyperglycaemia as diabetes. Objective: The objective of this study was to determine and compare the prevalence of hyperglycaemia (diabetes and impaired glucose regulation (IGR)) in TB patients and to assess the cross-sectional association between TB and hyperglycaemia at enrolment and after three months of follow-up. Methods: Consecutive adult TB and non-TB participants presenting at a TB clinic in Cape Town were enrolled in this cross-sectional study and follow-up between July 2013 and August 2015. Diabetes was defined as self-reported diabetes, fasting plasma glucose (FPG) ≥ 7.0 mmol·L⁻¹ or glycated haemoglobin (HbA1c) ≥ 6.5%. IGR was defined as FPG 5.5– < 7.0 mmol·L⁻¹ or HbA1c 5.7– < 6.5%. TB patients initiated treatment. After three months, all participants were followed up and screened for diabetes again. The association between TB and hyperglycaemia was assessed using logistic regression adjusting for potential confounders including sex, age, income, hypertension, waist circumference, previous prisoner, marital status, work status, HIV status. Results: Diabetes screening was performed in 852 participants (414 TB and 438 non-TB) at enrolment and in 639 (304 TB and 335 non-TB) at three-month follow-up. The prevalence of HIV-1 infection was 69.6% (95% confidence interval (CI), 64.9–73.8 %) among TB patients, and 58.2% (95% CI, 53.5–62.8 %) among the non-TB participants. Glycaemic levels were much higher in TB patients than in the non-TB participants but decreased over time. Among TB patients, the prevalence of IGR was 65.2% (95% CI 60.1 - 69.9) at enrollment and 21.5% (95% CI 17.2-26.5) at follow-up; and was 50% (45.1 - 54.94) and 32% (95% CI 27.9 - 38.0) respectively, among non-TB participants. The prevalence of diabetes in TB patients was 12.5% (95% CI 9.69 – 16.12%) at enrolment and 9.2% (95% CI, 6.43–13.03%) at follow-up; and was 10.04% (95% CI, 7.55–13.24%) and 8.06% (95% CI, 5.58–11.51) respectively, among non-TB participants. The association between TB and IGT was significant at enrolment (adjusted odds ratio (OR) 2.26 (95% CI, 1.55-3.31) but disappeared at follow-up 0.84 (0.53 - 1.36). However, the TB-diabetes association remained positive and significant both at enrolment (2.41 (95% CI, 1.3-4.34)) and follow-up (OR 3.31 (95% CI, 1.5 - 7.25)). Conclusion: Transient hyperglycaemia exists during tuberculosis. This has implications on diabetes screening in TB patients and suggests a need for diabetes confirmation tests during or after TB treatment. Nonetheless, the association between TB and diabetes noted at enrolment persists at 3 months highlighting the importance of diabetes control and prevention for TB control. Further research is required to investigate the impact of hyperglycaemia (transient or otherwise) on TB outcomes to ascertain the clinical significance of hyperglycemia at enrolment.

Keywords: diabetes, impaired glucose regulation, transient hyperglycaemia, tuberculosis

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Tiago Sigal Linhares, Ana Amélia Nascimento da Silva Bones, Juliana Miola, McArthur Alexander Barrow, Airton Tetelbom Stein

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Introduction: As a result of increased globalization and changing migration trends, it is expected that a significant portion of People Living with HIV/AIDS (PLWHA) will change their place of residence over time. In order to provide better health care, monitor the HIV epidemic and plan urban public health care and policies, there is a growing need to formulate a strategy for monitoring PLWHA care, location and migration patterns. The Porto Alegre District is characterized by a high prevalence of PLWHA and is considered one of the epicenters of HIV epidemic in Latin America. Objectives: The aim of this study is to create a digital and easily editable map in order to create a visual representation of the location of PLWHA and to monitor their migration within the city and the country in an effort to promote longitudinal care. Methods: This Experience Report used Google Maps Map Creator to generate an active digital map showing the location and changes in residence of 165 PLWHA who received care at two Primary Health Care (PHC) clinics, which attended an estimated population of five thousand patients, in downtown Porto Alegre over the last four years. Their current addresses were discovered in the unified Brazilian health care system digital records (e-SUS) and updated on the map. Results: A digital map with PLWHA current residence location was created. It was possible to demonstrate visually areas with a large concentration of PLWHA and the migration of the population within the city as wells as other cities, regions and states. Conclusions: An easily reproducible and free map could aid in PLWHA monitoring, urban public health planning, target interventions and situational diagnosis. Moreover, a visual representation of PLWHA location and migration could help bring more attention and investments to areas with geographic inequities or higher prevalence of PLWHA. It also enables notification of local PHC units of monitored patients inside their area, which are in clinical risk or with treatment abandonment through active case findings, improving the care of PLWHA.

Keywords: health care, medical public health, theoretical and conceptual innovations, urban public health

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Authors: Madhusudana S. N., Reeta Mani, Ashwini S. Satishchandra P., Netravati, Udhani V., Fiaz A., Karande S.

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Rabies is an acute encephalitis which is considered 100% fatal despite occasional reports of survivors. However, in recent times more cases of human rabies survivors are being reported. In the last 5 years, there are six laboratories confirmed human rabies survivors in India alone. All cases were children below 15 years and all contracted the disease by dog bites. All of them also had received the full or partial course of rabies vaccination and 4 out of 6 had also received rabies immunoglobulin. All cases were treated in intensive care units in hospitals at Bangalore, Mumbai, Chandigarh, Lucknow and Goa. We report here the results of immunological and virological studies conducted at our laboratory on these patients. The clinical samples that were obtained from these patients were Serum, CSF, nuchal skin biopsy and saliva. Serum and CSF samples were subjected to standard RFFIT for estimation of rabies neutralizing antibodies. Skin biopsy, CSF and saliva were processed by TaqMan real-time PCR for detection of viral RNA. CSF, saliva and skin homogenates were also processed for virus isolation by inoculation of suckling mice. The PBMCs isolated from fresh blood was subjected to ELISPOT assay to determine the type of immune response (Th1/Th2). Both CSF and serum were also investigated for selected cytokines by Luminex assay. The level of antibodies to virus G protein and N protein were determined by ELISA. All survivors had very high titers of RVNA in serum and CSF 100 fold higher than non-survivors and vaccine controls. A five-fold rise in titer could be demonstrated in 4 out of 6 patients. All survivors had a significant increase in antibodies to G protein in both CSF and serum when compared to non-survivors. There was a profound and robust Th1 response in all survivors indicating that interferon gamma could play an important factor in virus clearance. We could isolate viral RNA in only one patient four years after he had developed symptoms. The partial N gene sequencing revealed 99% homology to species I strain prevalent in India. Levels of selected cytokines in CSF and serum did not reveal any difference between survivors and non-survivors. To conclude, survival from rabies is mediated by virus-specific immune responses of the host and clearance of rabies virus from CNS may involve the participation of both Th2 and Th1 immune responses.

Keywords: rabies, rabies treatment, rabies survivors, immune reponse in rabies encephalitis

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Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

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The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

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Authors: Zbigniew Izdebski, Alicja Kozakiewicz, Maciej Białorudzki, Joanna Mazur

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Work is an extremely important part of everyone's life and affects functioning in daily life. Healthcare workers (HCW) are suffering from negative actions in and out of the workplace, such as harassment, abuse, long working hours, mental suffering, exhaustion, and professional burnout. Staff burnout is detrimental not only in terms of individual employees but also to working with patients and to the healthcare institution as a whole. The purpose of this study was to explore the level of professional burnout among HCW working in medical institutions during the COVID-19 pandemic in Poland. The extent to which selected sociodemographic factors and perceived stress increase the risk of professional burnout was assessed. In addition, the frequency of use of professional psychological help and less formal support groups by HCW in relation to the level of professional burnout was presented. The survey was conducted as part of a larger project on the humanization of medicine and clinical communication from February-April 2022. This study used a self-administered online survey (CAWI) technique and PAPI (pen and paper interview) technique. The BAT-12 scale was used to measure burnout, the PSS-4 scale was used to measure stress, and questions formulated by the research team were also used. For the purpose of analysis, the sample was limited to 2196 HCWs who worked on a daily basis with patients during the COVID-19 pandemic. Frequency distributions were analyzed, and multivariate logistic regression was performed. The mean scores (scores) of job burnout as measured by the BAT-12 scale ranged among the professional groups from 2.15(0.69) to 2.30 (0.69) and remained highest for the nurses' group. The groups differed significantly in levels of burnout (chi-sq=17.719; d.f.=8; p<0.023). In the final model, raised stress most likely increased the risk of burnout (OR=3.88; 95%CI <3.13-3.81>; p<0,001). Other significant predictors of burnout included: traumatic work-related experience (OR=1.91, p<0.001), mobbing (OR=1.83, p<0.001), and a higher workload than before the pandemic (OR=1.41, p=0.002). Only 7% of respondents decided to use various forms of psychological support during the pandemic. HCW experiences challenges in dealing with an unpredictable pandemic. Limited preparedness can lead to physical and psychological problems such as high-stress levels, anxiety, fear, helplessness, hopelessness, anger and stigma. The workload can lead to professional burnout, as well as threaten patient safety.

Keywords: burnout, work, healthcare, healthcare worker, stress

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Authors: Ananya Hazare, Ranjit Kamble

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Introduction: Patients with Cleft lip and palate (CL/P) can present with a maxillary retrution after cleft repair. Anterior Maxillary distraction osteogenesis (AMD) is a technique that provides simultaneous skeletal advancement and expansion of the soft tissues related to an anterior segment of the maxilla. This case presented is a case of AMD. The advantage of this technique is that the occlusion in the posterior segment can be maintained, and only the segment in cross bite is advanced for correction of the midfacial deficiency. The other alternative treatment is anterior movement by a Lefort 1 osteotomy. When a Lefort 1 osteotomy is compared with the Distraction osteogenesis or AMD, the disadvantages of the Le Fort 1 include a higher risk of morbidity, requirement of fixation, relapse tendency and unexpected changes in the nasal form. These complications were eliminated by AMD technique. This was followed by placement of the implant in the bone formed after AMD. Hence complete surgical, orthodontic and prosthodontics rehabilitation of the patient was done by an interdisciplinary approach. Methods: Patient presented with repaired UCL/P of the right side with midfacial retrusion. Intro-oral examination revealed a good occlusion in the posterior arch and anterior Crossbite from canine to canine. Patient's both maxillary lateral incisors were missing. The lower arch was well aligned with all teeth present. The study models when scored according to GOSLON yardstick received a score of 4. After pre-surgical orthodontic phase was completed an intraoral distractor was fabricated by modification of HYRAX expansion screw. After surgery, low subapical osteotomy cuts were placed and the distractor was fixed. The latency period of 5 days was observed after which the distraction was started. Distraction was done at a rate of 1 mm/day with a rhythm of 0.5mm in morning and 0.5mm in the evening. The total distraction of 12 mm was done. After a consolidation period, the distractor was removed, and retention by a removable partial denture was given. Radiographic examination confirmed mature bone formation in the distracted segment. Implants were placed and allowed to osseointegrate for approximately 4 months and were then loaded with abutments. Results: Total distraction done was 12mm and after relapse it was 8mm. After consolidation phase the radiographic examination revealed a B2 quality of bone according to the Misch's classification and sufficient height from the maxillary sinus. These findings were indicative for placement of implants in the distracted bone formed in premolar region. Implants were placed and after radiographic evidence of osseointegration was seen they were loaded with abutments. Thus resulting in a complete rehabilitation of a cleft patient by an interdisciplinary approach. Conclusion: Anterior maxillary distraction can be used as an alternative method instead of complete distraction osteogenesis or Lefort 1 advancement of maxilla in cases where the advancement needed is minimum. Use of HYRAX expansion screw modified as intra-oral distractor can be used in such cases, which significantly reduces the cost of treatment, as expensive distractors are not used. This technique is very useful and efficient in countries like India where the patient cannot afford expensive treatment options.

Keywords: cleft lip and palate, distraction osteogenesis, anterior maxillary distraction, orthodontics and dentofacial orthopaedics, hyrax expansion screw modification

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Authors: Shamini Dhana, G. Subrahmanya VRK Rao

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The fashion industry is advancing towards a mindset of zero waste, personalization, creativity, and circularity. The trend of upcycling clothing and materials into personalized fashion is being demanded by the next generation. There is a need for a digital tool to accelerate the process towards mass customization. Dhana’s D/Sphere fashion technology platform uses digital tools to accelerate upcycling. In essence, advanced fashion garments can be designed and developed via reuse, repurposing, recreating activities, and using existing fabric and circulating materials. The D/Sphere platform has the following objectives: to provide (1) An opportunity to develop modern fashion using existing, finished materials and clothing without chemicals or water consumption; (2) The potential for an everyday customer and designer to use the medium of fashion for creative expression; (3) A solution to address the global textile waste generated by pre- and post-consumer fashion; (4) A solution to reduce carbon emissions, water, and energy consumption with the participation of all stakeholders; (5) An opportunity for brands, manufacturers, retailers to work towards zero-waste designs and as an alternative revenue stream. Other benefits of this alternative approach include sustainability metrics, trend prediction, facilitation of disassembly and remanufacture deep learning, and hyperheuristics for high accuracy. A design tool for mass personalization and customization utilizing existing circulating materials and deadstock, targeted to fashion stakeholders will lower environmental costs, increase revenues through up to date upcycled apparel, produce less textile waste during the cut-sew-stitch process, and provide a real design solution for the end customer to be part of circular fashion. The broader impact of this technology will result in a different mindset to circular fashion, increase the value of the product through multiple life cycles, find alternatives towards zero waste, and reduce the textile waste that ends up in landfills. This technology platform will be of interest to brands and companies that have the responsibility to reduce their environmental impact and contribution to climate change as it pertains to the fashion and apparel industry. Today, over 70% of the $3 trillion fashion and apparel industry ends up in landfills. To this extent, the industry needs such alternative techniques to both address global textile waste as well as provide an opportunity to include all stakeholders and drive circular fashion with new personalized products. This type of modern systems thinking is currently being explored around the world by the private sector, organizations, research institutions, and governments. This technological innovation using digital tools has the potential to revolutionize the way we look at communication, capabilities, and collaborative opportunities amongst stakeholders in the development of new personalized and customized products, as well as its positive impacts on society, our environment, and global climate change.

Keywords: circular fashion, deep learning, digital technology platform, personalization

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Authors: Varsha Salian, Shama Rao, N. Narendra, B. Mohana Kumar

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Evolving evidence proposes the existence of a highly tumorigenic subpopulation of undifferentiated, self-renewing cancer stem cells, responsible for exhibiting resistance to conventional anti-cancer therapy, recurrence, metastasis and heterogeneous tumor formation. Importantly, the mechanisms exploited by cancer stem cells to resist chemotherapy are very less understood. Oral squamous cell carcinoma (OSCC) is one of the most regularly diagnosed cancer types in India and is associated commonly with alcohol and tobacco use. Therefore, the isolation and in vitro characterization of cancer stem-like cells from patients with OSCC is a critical step to advance the understanding of the chemoresistance processes and for designing therapeutic strategies. With this, the present study aimed to establish and characterize cancer stem-like cells in vitro from OSCC. The primary cultures of cancer stem-like cell lines were established from the tissue biopsies of patients with clinical evidence of an ulceroproliferative lesion and histopathological confirmation of OSCC. The viability of cells assessed by trypan blue exclusion assay showed more than 95% at passage 1 (P1), P2 and P3. Replication rate was performed by plating cells in 12-well plate and counting them at various time points of culture. Cells had a more marked proliferative activity and the average doubling time was less than 20 hrs. After being cultured for 10 to 14 days, cancer stem-like cells gradually aggregated and formed sphere-like bodies. More spheroid bodies were observed when cultured in DMEM/F-12 under low serum conditions. Interestingly, cells with higher proliferative activity had a tendency to form more sphere-like bodies. Expression of specific markers, including membrane proteins or cell enzymes, such as CD24, CD29, CD44, CD133, and aldehyde dehydrogenase 1 (ALDH1) is being explored for further characterization of cancer stem-like cells. To summarize the findings, the establishment of OSCC derived cancer stem-like cells may provide scope for better understanding the cause for recurrence and metastasis in oral epithelial malignancies. Particularly, identification and characterization studies on cancer stem-like cells in Indian population seem to be lacking thus provoking the need for such studies in a population where alcohol consumption and tobacco chewing are major risk habits.

Keywords: cancer stem-like cells, characterization, in vitro, oral squamous cell carcinoma

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Authors: Suehyun Cho, Darrell Harrington, Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Alex Kiselyov, Michael Shpigelmacher

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The Dandy-Walker malformation (DWM) represents a clinical syndrome manifesting as a combination of posterior fossa cyst, hypoplasia of the cerebellar vermis, and obstructive hydrocephalus. Anatomic hallmarks include hypoplasia of the cerebellar vermis, enlargement of the posterior fossa, and cystic dilatation of the fourth ventricle. Current treatments of DWM, including shunting of the cerebral spinal fluid ventricular system and endoscopic third ventriculostomy (ETV), are frequently clinically insufficient, require additional surgical interventions, and carry risks of infections and neurological deficits. Bionaut Labs develops an alternative way to treat Dandy-Walker Malformation (DWM) associated with non-communicating hydrocephalus. We utilize our discreet microsurgical Bionaut™ particles that are controlled externally and remotely to perform safe, accurate, effective fenestration of the Dandy-Walker cyst, specifically in the posterior fossa of the brain, to directly normalize intracranial pressure. Bionaut™ allows for complex non-linear trajectories not feasible by any conventional surgical techniques. The microsurgical particle safely reaches targets in the lower occipital section of the brain. Bionaut™ offers a minimally invasive surgical alternative to highly involved posterior craniotomy or shunts via direct fenestration of the fourth ventricular cyst at the locus defined by the individual anatomy. Our approach offers significant advantages over the current standards of care in patients exhibiting anatomical challenge(s) as a manifestation of DWM, and therefore, is intended to replace conventional therapeutic strategies. Current progress, including platform optimization, Bionaut™ control, and real-time imaging and in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of ovine models, will be discussed.

Keywords: Bionaut™, cerebral spinal fluid, CSF, cyst, Dandy-Walker, fenestration, hydrocephalus, micro-robot

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Authors: Chuyu Huang, Itsuki Minemi, Kuanlin Chen, Yuki Hirose

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It remains unclear how language speakers are able to perceive phonological contrasts that do not exist on their own. This experiment uses the vowel-length distinction in Japanese, which is phonologically contrastive and co-occurs with tonal change in some cases. For speakers whose first language does not distinguish vowel length, contrastive duration is usually misperceived, e.g., Mandarin speakers. Two alternative hypotheses for how Mandarin speakers would perceive a phonological contrast that does not exist in their language make different predictions. The stress parameter model does not have a clear prediction about the impact of tonal type. Mandarin speakers will likely be not able to perceive vowel length as well as Japanese native speakers do, but the performance might not correlate to tonal type because the prosody of their language is distinctive, which requires users to encode lexical prosody and notice subtle differences in word prosody. By contrast, cue-based phonetic models predict that Mandarin speakers may rely on pitch differences, a secondary cue, to perceive vowel length. Two groups of Mandarin speakers, including naive non-Japanese speakers and beginner learners, were recruited to participate in an AX discrimination task involving two Japanese sound stimuli that contain a phonologically contrastive environment. Participants were asked to indicate whether the two stimuli containing a vowel-length contrast (e.g., maapero vs. mapero) sound the same. The experiment was bifactorial. The first factor contrasted three syllabic positions (syllable position; initial/medial/final), as it would be likely to affect the perceptual difficulty, as seen in previous studies, and the second factor contrasted two pitch types (accent type): one with accentual change that could be distinguished with the lexical tones in Mandarin (the different condition), with the other group having no tonal distinction but only differing in vowel length (the same condition). The overall results showed that a significant main effect of accent type by applying a linear mixed-effects model (β = 1.48, SE = 0.35, p < 0.05), which implies that Mandarin speakers tend to more successfully recognize vowel-length differences when the long vowel counterpart takes on a tone that exists in Mandarin. The interaction between the accent type and the syllabic position is also significant (β = 2.30, SE = 0.91, p < 0.05), showing that vowel lengths in the different conditions are more difficult to recognize in the word-final case relative to the initial condition. The second statistical model, which compares naive speakers to beginners, was conducted with logistic regression to test the effects of the participant group. A significant difference was found between the two groups (β = 1.06, 95% CI = [0.36, 2.03], p < 0.05). This study shows that: (1) Mandarin speakers are likely to use pitch cues to perceive vowel length in a non-native language, which is consistent with the cue-based approaches; (2) an exposure effect was observed: the beginner group achieved a higher accuracy for long vowel perception, which implied the exposure effect despite the short period of language learning experience.

Keywords: cue-based perception, exposure effect, prosodic perception, vowel duration

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Authors: Camila Lemos Pinto, Juliana Alves Carneiro, Patrícia Borges Botelho, João Felipe Mota

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Sarcopenia, a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength, currently affects over 50 million people and increases the risk of adverse outcomes such as physical disability, poor quality of life and death. The aim of this study was to examine the efficacy of creatine supplementation associated with resistance training on muscle mass in the elderly. A 12-week, double blind, randomized, parallel group, placebo controlled trial was conducted. Participants were randomly allocated into one of the following groups: placebo with resistance training (PL+RT, n=14) and creatine supplementation with resistance training (CR + RT, n=13). The subjects from CR+RT group received 5 g/day of creatine monohydrate and the subjects from the PL+RT group were given the same dose of maltodextrin. Participants were instructed to ingest the supplement on non-training days immediately after lunch and on training days immediately after resistance training sessions dissolved in a beverage comprising 100 g of maltodextrin lemon flavored. Participants of both groups undertook a supervised exercise training program for 12 weeks (3 times per week). The subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle mass, assessed by dual energy X-ray absorptiometry (DXA). The secondary outcome included diagnose participants with one of the three stages of sarcopenia (presarcopenia, sarcopenia and severe sarcopenia) by skeletal muscle mass index (SMI), handgrip strength and gait speed. CR+RT group had a significant increase in SMI and muscle (p<0.0001), a significant decrease in android and gynoid fat (p = 0.028 and p=0.035, respectively) and a tendency of decreasing in body fat (p=0.053) after the intervention. PL+RT only had a significant increase in SMI (p=0.007). The main finding of this clinical trial indicated that creatine supplementation combined with resistance training was capable of increasing muscle mass in our elderly cohort (p=0.02). In addition, the number of subjects diagnosed with one of the three stages of sarcopenia at baseline decreased in the creatine supplemented group in comparison with the placebo group (CR+RT, n=-3; PL+RT, n=0). In summary, 12 weeks of creatine supplementation associated with resistance training resulted in increases in muscle mass. This is the first research with elderly of both sexes that show the same increase in muscle mass with a minor quantity of creatine supplementation in a short period. Future long-term research should investigate the effects of these interventions in sarcopenic elderly.

Keywords: creatine, dietetic supplement, elderly, resistance training

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Authors: May Fadheel Estephan, Richard Perks

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Context: Cancer is a serious health concern that affects millions of people worldwide. Early detection and treatment are essential for improving patient outcomes. However, current methods for cancer detection have limitations, such as low sensitivity and specificity. Research Aim: The aim of this study was to develop an optical sensor for cancer detection using elastic light scattering spectroscopy (ELSS). ELSS is a noninvasive optical technique that can be used to characterize the size and concentration of particles in a solution. Methodology: An optical probe was fabricated with a 100-μm-diameter core and a 132-μm centre-to-centre separation. The probe was used to measure the ELSS spectra of polystyrene spheres with diameters of 2, 0.8, and 0.413 μm. The spectra were then analysed to determine the size and concentration of the spheres. Findings: The results showed that the optical probe was able to differentiate between the three different sizes of polystyrene spheres. The probe was also able to detect the presence of polystyrene spheres in suspension concentrations as low as 0.01%. Theoretical Importance: The results of this study demonstrate the potential of ELSS for cancer detection. ELSS is a noninvasive technique that can be used to characterize the size and concentration of cells in a tissue sample. This information can be used to identify cancer cells and assess the stage of the disease. Data Collection: The data for this study were collected by measuring the ELSS spectra of polystyrene spheres with different diameters. The spectra were collected using a spectrometer and a computer. Analysis Procedures: The ELSS spectra were analysed using a software program to determine the size and concentration of the spheres. The software program used a mathematical algorithm to fit the spectra to a theoretical model. Question Addressed: The question addressed by this study was whether ELSS could be used to detect cancer cells. The results of the study showed that ELSS could be used to differentiate between different sizes of cells, suggesting that it could be used to detect cancer cells. Conclusion: The findings of this research show the utility of ELSS in the early identification of cancer. ELSS is a noninvasive method for characterizing the number and size of cells in a tissue sample. To determine cancer cells and determine the disease's stage, this information can be employed. Further research is needed to evaluate the clinical performance of ELSS for cancer detection.

Keywords: elastic light scattering spectroscopy, polystyrene spheres in suspension, optical probe, fibre optics

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Authors: Albert Amagyei, Julia Carroll, Amanda R. Amorim Adegboye, Laura Strumidlo, Rosie Kneafsey

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Introduction: Classroom-based learning has persisted as the mainstream model of pre-registration nurse education. This model is often rigid, teacher-centered, and unable to support active learning and the practical learning needs of nursing students. Health Education England (HEE), a public body of the Department of Health and Social Care, hypothesises that blended learning (BL) programmes may address health system and nursing profession challenges, such as nursing shortages and lack of digital expertise, by exploring opportunities for providing predominantly online, remote-access study which may increase nursing student recruitment, offering alternate pathways to nursing other than the traditional classroom route. This study will provide evidence for blended learning strategies adopted in nursing education as well as examine nursing student learning experiences concerning the challenges and opportunities related to using blended learning within nursing education. Objective: This review will explore the challenges and opportunities of BL within pre-registration nurse education from the student's perspective. Methods: The search was completed within five databases. Eligible studies were appraised independently by four reviewers. The JBI-convergent segregated approach for mixed methods review was used to assess and synthesize the data. The study’s protocol has been registered with the International Register of Systematic Reviews with registration number// PROSPERO (CRD42023423532). Results: Twenty-seven (27) studies (21 quantitative and 6 qualitative) were included in the review. The study confirmed that BL positively impacts nursing students' learning outcomes, as demonstrated by the findings of the meta-analysis and meta-synthesis. Conclusion: The review compared BL to traditional learning, simulation, laboratory, and online learning on nursing students’ learning and programme outcomes as well as learning behaviour and experience. The results show that BL could effectively improve nursing students’ knowledge, academic achievement, critical skills, and clinical performance as well as enhance learner satisfaction and programme retention. The review findings outline that students’ background characteristics, BL design, and format significantly impact the success of the BL nursing programme.

Keywords: nursing student, blended learning, pre-registration nurse education, online learning

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

Abstract:

The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: Dylan Santos De Pinho, Nabil Ouerhani

Abstract:

Energy consumption of machine-tools is becoming critical for machine-tool builders and end-users because of economic, ecological and legislation-related reasons. Many machine-tool builders are seeking for solutions that allow the reduction of energy consumption of machine-tools while preserving the same productivity rate and the same quality of machined parts. In this paper, we present the first results of a project conducted jointly by academic and industrial partners to reduce the energy consumption of a Swiss-Type lathe. We employ genetic algorithms to find optimal machining parameters – the set of parameters that lead to the best trade-off between energy consumption, part quality and tool lifetime. Three main machining process parameters are considered in our optimization technique, namely depth of cut, spindle rotation speed and material feed rate. These machining process parameters have been identified as the most influential ones in the configuration of the Swiss-type machining process. A state-of-the-art multi-objective genetic algorithm has been used. The algorithm combines three fitness functions, which are objective functions that permit to evaluate a set of parameters against the three objectives: energy consumption, quality of the machined parts, and tool lifetime. In this paper, we focus on the investigation of the fitness function related to energy consumption. Four different energy consumption related fitness functions have been investigated and compared. The first fitness function refers to the Kienzle cutting force model. The second fitness function uses the Material Removal Rate (RMM) as an indicator of energy consumption. The two other fitness functions are non-deterministic, learning-based functions. One fitness function uses a simple Neural Network to learn the relation between the process parameters and the energy consumption from experimental data. Another fitness function uses Lasso regression to determine the same relation. The goal is, then, to find out which fitness functions predict best the energy consumption of a Swiss-Type machining process for the given set of machining process parameters. Once determined, these functions may be used for optimization purposes – determine the optimal machining process parameters leading to minimum energy consumption. The performance of the four fitness functions has been evaluated. The Tornos DT13 Swiss-Type Lathe has been used to carry out the experiments. A mechanical part including various Swiss-Type machining operations has been selected for the experiments. The evaluation process starts with generating a set of CNC (Computer Numerical Control) programs for machining the part at hand. Each CNC program considers a different set of machining process parameters. During the machining process, the power consumption of the spindle is measured. All collected data are assigned to the appropriate CNC program and thus to the set of machining process parameters. The evaluation approach consists in calculating the correlation between the normalized measured power consumption and the normalized power consumption prediction for each of the four fitness functions. The evaluation shows that the Lasso and Neural Network fitness functions have the highest correlation coefficient with 97%. The fitness function “Material Removal Rate” (MRR) has a correlation coefficient of 90%, whereas the Kienzle-based fitness function has a correlation coefficient of 80%.

Keywords: adaptive machining, genetic algorithms, smart manufacturing, parameters optimization

Procedia PDF Downloads 142

Authors: Joulié Aurélien, Jourdain Elsa, Bailly Xavier, Gasqui Patrick, Yang Elise, Leblond Agnès, Rousset Elodie, Sidi-Boumedine Karim

Abstract:

Q fever is a worldwide zoonosis caused by the gram-negative obligate intracellular bacterium Coxiella burnetii. Following the recent outbreaks in the Netherlands, a hyper virulent clone was found to be the cause of severe human cases of Q fever. In livestock, Q fever clinical manifestations are mainly abortions. Although the abortion rates differ between ruminant species, C. burnetii’s virulence remains understudied, especially in enzootic areas. In this study, the infectious potential of three C. burnetii isolates collected from French farms of small ruminants were compared to the reference strain Nine Mile (in phase II and in an intermediate phase) using an in vivo (CD1 mice) model. Mice were challenged with 105 live bacteria discriminated by propidium monoazide-qPCR targeting the icd-gene. After footpad inoculation, spleen and popliteal lymph node were harvested at 10 days post-inoculation (p.i). The strain invasiveness in spleen and popliteal nodes was assessed by qPCR assays targeting the icd-gene. Preliminary results showed that the avirulent strains (in phase 2) failed to pass the popliteal barrier and then to colonize the spleen. This model allowed a significant differentiation between strain’s invasiveness on biological host and therefore identifying distinct virulence profiles. In view of these results, we plan to go further by testing fifteen additional C. burnetii isolates from French farms of sheep, goat and cattle by using the above-mentioned in vivo model. All 15 strains display distant MLVA (multiple-locus variable-number of tandem repeat analysis) genotypic profiles. Five of the fifteen isolates will bee also tested in vitro on ovine and bovine macrophage cells. Cells and supernatants will be harvested at day1, day2, day3 and day6 p.i to assess in vitro multiplication kinetics of strains. In conclusion, our findings might help the implementation of surveillance of virulent strains and ultimately allow adapting prophylaxis measures in livestock farms.

Keywords: Q fever, invasiveness, ruminant, virulence

Procedia PDF Downloads 356