Search

ObjectivesLimited research exists on COVID-19 associated brain fog, and on the long-term cognitive and psychiatric sequelae in racially and ethnically diverse patients. We characterize the neuropsychological sequelae of post-acute COVID-19 in a diverse cohort and investigate whether COVID-19 clinical severity remains associated with brain fog and cognitive deficits approximately 2 years post infection.MethodsA cross-sectional study of patients with a history of COVID-19 hospitalization (March-September 2020). COVID-19 clinical severity was indexed using the National Early Warning Score 2 and a comprehensive neuropsychological tele-battery was administered 2 years post discharge. Pearson's r correlations assessed association, while independent sample t-tests examined group differences. Significant outcomes were further analyzed using multiple regression and ANCOVAs, adjusting for key covariates.ResultsIn 41 adult patients (19 female, 30 Hispanic, 13 Black, mean age of 65 (SD = 15), COVID-19 level of severity was associated with greater number of endorsed brain fog symptoms (Pearson's r = .34, 95% CI [.04, .59]), worse overall cognitive functioning (global cognition: r = -.36, 95% CI [-.61, -.05]) and reduced performance on an attention and working memory task (digit span backwards: r = -.41, 95% CI [-.66, -.09]) at 2-year follow-up. Brain fog symptoms most associated with COVID-19 severity included difficulty focusing (r = .46, 95% CI [.18, .67]), detached (r = .41, 95% CI [.12, .64]) and feeling sleepy (r = .40, 95% CI [.11, .63]). Patients' cognitive performance was generally below average (global cognition z-score: M = -.96, SD = .66), with group differences based on sex and ethnicity evidenced on individual cognitive tests.DiscussionThis study emphasizes the importance of continued research on the long-term effects of COVID-19 infection on neuropsychological outcomes, particularly among underrepresented, health-disparate groups. Greater understanding of these associations could improve detection and treatment of those at increased risk of cognitive decline or impairment.

This study investigates the effectiveness of integrating short stories with task-based learning activities in English as a foreign language (EFL) class to promote vocabulary development and motivation among L2 learners. Six short stories were selected by the participants based on their interests, pre- and post-tests were conducted to evaluate vocabulary acquisition and a questionnaire was used to gather information about the perception of task-based activities after reading short stories among students. The study involved 60 intermediate level English students at the SEEU Language Center, assigned to either the control or experimental group. The experimental group completed post-reading tasks such as keeping vocabulary notebooks, reading circle discussions, sequencing activities, plot structure understanding, and group poster presentations after reading each story. The findings suggest that the incorporating engaging reading activities had a favorable effect on language learning. The experimental group exhibited greater vocabulary acquisition and comprehension than the control group. The follow-up tasks created a sense of achievement, improved communication and interaction among the students. According to the study, including comprehensible input through extensive reading along with constructive output from task-oriented exercises can effectively promote language progress and enhance students’ motivation thus effectively facilitating language development in L2 learners.

Damià Valero-Bover,1,2 David Monterde,2,3 Gerard Carot-Sans,1,2 Miguel Cainzos-Achirica,4,5 Josep Comin-Colet,6– 8 Emili Vela,1,2 Montse Clèries,1,2 Júlia Folguera,1,2 Sònia Abilleira,9 Miquel Arrufat,3 Yolanda Lejardi,3 Òscar Solans,2,10 Toni Dedeu,11 Marc Coca,1,2 Pol Pérez-Sust,1 Caridad Pontes,1,2,12 Jordi Piera-Jiménez1,2,13 1Catalan Health Service, Barcelona, Spain; 2Digitalization for the Sustainability of the Healthcare System (DS3) – Institut d’Investigacions Biomèdiques de Bellvitge (IDIBELL), Barcelona, Spain; 3Catalan Institute of Health, Barcelona, Spain; 4Center for Outcomes Research, Houston Methodist, Houston, TX, USA; 5Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 6Cardiology Department, Bellvitge University Hospital (IDIBELL), Barcelona, Spain; 7Department of Medicine, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain; 8CIBER Cardiovascular (CIBERCV), L’Hospitalet de Llobregat, Barcelona, Spain; 9CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; 10Health Department, eHealth Unit, Barcelona, Spain; 11WHO European Centre for Primary Health Care, Almaty, Kazakhstan; 12Department of Pharmacology, Autonomous University of Barcelona, Barcelona, Spain; 13Faculty of Informatics, Telecommunications and Multimedia, Universitat Oberta de Catalunya, Barcelona, SpainCorrespondence: Jordi Piera-Jiménez, Catalan Health Service, Gran Via de les Corts Catalanes 587, Barcelona, 08007, Spain, Tel +34 93 403 85 85, Email jpiera@catsalut.catPurpose: To assess the contribution of age and comorbidity to the risk of critical illness in hospitalized COVID-19 patients using increasingly exhaustive tools for measuring comorbidity burden.Patients and Methods: We assessed the effect of age and comorbidity burden in a retrospective, multicenter cohort of patients hospitalized due to COVID-19 in Catalonia (North-East Spain) between March 1, 2020, and January 31, 2022. Vaccinated individuals and those admitted within the first of the six COVID-19 epidemic waves were excluded from the primary analysis but were included in secondary analyses. The primary outcome was critical illness, defined as the need for invasive mechanical ventilation, transfer to the intensive care unit (ICU), or in-hospital death. Explanatory variables included age, sex, and four summary measures of comorbidity burden on admission extracted from three indices: the Charlson index (17 diagnostic group codes), the Elixhauser index and count (31 diagnostic group codes), and the Queralt DxS index (3145 diagnostic group codes). All models were adjusted by wave and center. The proportion of the effect of age attributable to comorbidity burden was assessed using a causal mediation analysis.Results: The primary analysis included 10,551 hospitalizations due to COVID-19; of them, 3632 (34.4%) experienced critical illness. The frequency of critical illness increased with age and comorbidity burden on admission, irrespective of the measure used. In multivariate analyses, the effect size of age decreased with the number of diagnoses considered to estimate comorbidity burden. When adjusting for the Queralt DxS index, age showed a minimal contribution to critical illness; according to the causal mediation analysis, comorbidity burden on admission explained the 98.2% (95% CI 84.1– 117.1%) of the observed effect of age on critical illness.Conclusion: Comorbidity burden (when measured exhaustively) explains better than chronological age the increased risk of critical illness observed in patients hospitalized with COVID-19.Keywords: COVID-19, comorbidities, comorbidity burden, risk assessment, hospitalized patients, case-mix tool

By analyzing an understudied type of comparative, namely, subcomparatives with surface-phrasal standards of comparison, this article offers an answer to three long-debated questions regarding the internal structure and semantic composition of comparative constructions in opposition to traditional assumptions and reductionist analyses. First I offer syntactic tests evidencing the non-clausal status of the standard in these subcomparatives in Basque, Spanish and English. Second, regarding the question of the linkage type between the compared elements (either a dependence relation or a coordination relation), I present previous and novel syntactic evidence showing that phrasal subcomparatives invariably behave like common phrasal coordinates. Therefore, I defend an architecture of these comparatives involving a phrasal coordinate structure and offer a transparent mapping between the surface syntax and semantic interpretation of these constructions. Third, subcomparatives involve the obligatory omission of a measure modifier from the standard. This process known as comparative subdeletion cannot be explained as the result of wh-movement within a clause, given the non-clausal status of the standard. Alternatively, comparative subdeletion is defined not as an ad hoc deletion rule but rather as the result of an obligatory deletion operation independently attested in common coordinate structures.

Sophia W Light,1 Allison Pack,1 Alyssa Vela,2 Stacy C Bailey,1 Andrea Zuleta,1 Rachel O’Conor,1 Michael S Wolf1 1Division of General Internal Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; 2Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USACorrespondence: Sophia W Light, Center for Applied Health Research on Aging (CAHRA), Division of General Internal Medicine, Northwestern University Feinberg School of Medicine, 750 N. Lake Shore Drive, 10th Floor, Chicago, IL, 60611, USA, Tel +1(312)503-5015, Email sophia.wl@northwestern.eduPurpose: Historically marginalized communities disproportionately impacted by the pandemic are demonstrating lower uptake of COVID-19 vaccines. To facilitate the development of culturally tailored, language concordant educational materials promoting COVID-19 vaccination, we first explored older Latinx adults’ awareness, attitudes, and beliefs about COVID-19 vaccines and factors involved in vaccination decisions within their communities.Patients and Methods: Individual, semi-structured interviews were conducted with 15 participants who self-identified as Latinx/Hispanic, aged 50 and older, and living in Chicago. Eight interviews were conducted in English and seven in Spanish. Thematic analysis was used to analyze participants’ responses.Results: Participants revealed four key factors influencing vaccination decisions: 1. protecting oneself and loved ones (against COVID-19 (n=14), or from perceived dangers of the vaccine (n=9)); 2. trust in authorities (trusting information (n=9), or worrying the vaccine is being manipulated (n=5)); 3. access and availability (gratitude to live in a country where vaccines are available (n=5), or fear of going to vaccination sites due to immigration and insurance status (n=4)); and 4. Employment and semblance of normalcy (vaccination to create opportunities (n=6), or concern about missing out due to side effects (n=9)).Conclusion: Our findings illuminate key factors influencing decisions for COVID-19 vaccination among Latinx older adults in Chicago. Vaccination information aiming to increase vaccination rates among this important population may benefit from leveraging collective pronouns and spirituality, language concordance, low-tech options, building trust, and addressing insurance and immigration doubts. Next steps include developing educational materials based on these themes, followed by dissemination and evaluation. Lessons learned may be of interest to public health experts responding to the ongoing pandemic and other public health crises experienced by historically marginalized communities.Keywords: qualitative, COVID-19 vaccines, COVID-19, Latinx, older adult

Capital Appreciation Ltd v First National Nominees (Pty) Ltd 2022 ZASCA 85 The connection between share re-acquisitions, schemes of arrangement, and appraisal rights under the Companies Act 71 of 2008

In the present study, the effect of various weight percentages (0, 20, 30, and 40 wt.%) of Tungsten Carbide (WC) reinforcement in the Nickel-Chromium (Ni-Cr) alloy was investigated. The coatings were deposited on a 316L stainless steel substrate using Plasma Transferred Arc Welding (PTAW) process. Additionally, the As Welded (AW) NiCr-WC coatings were subjected to Short Time Heat-Treatment (STHT) and Laser Re-Melting (LRM) processes and a comparative study has been carried out with that of AW coatings. X-ray Diffraction (XRD), Scanning Electron Microscope (SEM), Vickers hardness and Pin on disc wear testing facilities were employed to characterize the phase structures, microstructure, dilution, crystallization, hardness and wear properties of the deposits. Wear mechanisms were studied using the 3D surface analyzer and SEM images. The STHT and LRM coatings showed an increased hardness and more crystalline phases than the As-Welded (AW) coatings. The correlation between the intermetallic phases, residual stress, microstructural evolution and friction-wear behaviour among the AW, STHT and LRM NiCr and NiCr-WC coatings were discussed in detail.

The present study aims to determine if the successful implementation of a blended learning methodology is more dependent on the course subject matter or on the teacher. Using the Evaluation Scale on the Influence of Course Subject and Teachers on B-learning, we analyzed five factors: Expectations, Web Tools 2.0, Feedback, Cooperative/collaborative Learning, and Social Relations. The results show that student expectations and cooperative/collaborative learning are dependent on the course subject matter while all five factors crucially depend on the role of the teacher. We concluded that teachers have a much greater influence than the course subject on the successful implementation of an effective blended learning model.

David Monterde,1,2 Gerard Carot-Sans,2,3 Miguel Cainzos-Achirica,4,5 Sònia Abilleira,1,6 Marc Coca,2,3 Emili Vela,2,3 Montse Clèries,2,3 Damià Valero-Bover,2,3 Josep Comin-Colet,7– 9 Luis García-Eroles,2,3 Pol Pérez-Sust,3 Miquel Arrufat,1 Yolanda Lejardi,1 Jordi Piera-Jiménez2,3,10 1Catalan Institute of Health, Barcelona, Spain; 2Digitalization for the Sustainability of the Healthcare System (DS3), Sistema de Salut de Catalunya, Barcelona, Spain; 3Servei Català de la Salut, Barcelona, Spain; 4Center for Outcomes Research, Houston Methodist, Houston, TX, USA; 5Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medical Institutions, Baltimore, MD, USA; 6CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; 7Department of Cardiology, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain; 8Bioheart-Cardiovascular Diseases Research Group (Idibell), L’Hospitalet de Llobregat, Barcelona, Spain; 9Department of Clinical Sciences, School of Medicine, Universität de Barcelona - UB, L’Hospitalet de Llobregat, Barcelona, Spain; 10Open Evidence Research Group, Universitat Oberta de Catalunya, Barcelona, SpainCorrespondence: Jordi Piera-JiménezServei Català de la Salut (CatSalut), Travessera de les Corts, 131-159 (Edifici Olímpia), Barcelona, 08028, SpainTel +34 634283110Email jpiera@catsalut.catBackground: Comorbidity burden has been identified as a relevant predictor of critical illness in patients hospitalized with coronavirus disease 2019 (COVID-19). However, comorbidity burden is often represented by a simple count of few conditions that may not fully capture patients’ complexity.Purpose: To evaluate the performance of a comprehensive index of the comorbidity burden (Queralt DxS), which includes all chronic conditions present on admission, as an adjustment variable in models for predicting critical illness in hospitalized COVID-19 patients and compare it with two broadly used measures of comorbidity.Materials and Methods: We analyzed data from all COVID-19 hospitalizations reported in eight public hospitals in Catalonia (North-East Spain) between June 15 and December 8 2020. The primary outcome was a composite of critical illness that included the need for invasive mechanical ventilation, transfer to ICU, or in-hospital death. Predictors including age, sex, and comorbidities present on admission measured using three indices: the Charlson index, the Elixhauser index, and the Queralt DxS index for comorbidities on admission. The performance of different fitted models was compared using various indicators, including the area under the receiver operating characteristics curve (AUROCC).Results: Our analysis included 4607 hospitalized COVID-19 patients. Of them, 1315 experienced critical illness. Comorbidities significantly contributed to predicting the outcome in all summary indices used. AUC (95% CI) for prediction of critical illness was 0.641 (0.624– 0.660) for the Charlson index, 0.665 (0.645– 0.681) for the Elixhauser index, and 0.787 (0.773– 0.801) for the Queralt DxS index. Other metrics of model performance also showed Queralt DxS being consistently superior to the other indices.Conclusion: In our analysis, the ability of comorbidity indices to predict critical illness in hospitalized COVID-19 patients increased with their exhaustivity. The comprehensive Queralt DxS index may improve the accuracy of predictive models for resource allocation and clinical decision-making in the hospital setting.Keywords: comorbidity, multimorbidity, COVID-19, hospitalization, risk

The present study reports the effect of WC particle (20%, 30%, and 40%) and secondary processes (Heat Treatment and Laser Treatment) on the mechanical properties of NiCrBSi and NiCrBSi–WC deposits. A detailed comparative analysis of As Welded (AW), Heat Treated (HT) and Laser Treated (LT) deposits was made in terms of morphology, interface thickness, hardness, residual stress, tensile and flexural strength. Higher surface hardness was obtained for Laser treated NiCrBSi–WC(40%) deposits as compared to the heat-treated and as-welded deposits. The higher weight percentage of WC particles modified the solidification pattern and stress distribution in the NiCrBSi matrix, which eventually decreased the mechanical strength of NiCrBSi–WC (40%) deposits. In addition, fractographic examinations were used to delineate the various toughening mechanisms present in the post-treated NiCrBSi and NiCrBSi–WC deposits.

Genetic disorders of the dentin are known for several years, and reviews have been published mainly in the form of case reports. Dentinogenesis imperfecta (DI) is a disease characterized by an abnormal formation and abnormal structure of the dentin, generally affecting both primary and permanent dentition. The only epidemiological data available were published in 1975 by Witkop, who estimated the incidence of dentinogenesis imperfecta to be between 1/6000 and 1/8000. We present a case of DI III with an unusual presentation of rhizomegaly, dilacerations of the root, and taurodontism, seldom reported in the English literature for any genetic disorder of dentin. Clinical management is challenging in such cases, as the literature mentions that only an early diagnosis and early treatment with periodic follow-up can help improve the quality of life. Psychological and genetic counseling along with a multidisciplinary approach is mandatory for the cases such as the one presented here. Patient education and motivation had a paramount role in making the patient accept the treatment.

Debris flows are one of the most frequent and dangerous phenomena affecting the Alpine environment; they are responsible of 36% of casualties due to gravitational phenomena in the Italian Alps during the last century. In the Western Italian Alps (Piemonte, Italy) a Territorial Debris Flow Early Warning System (Te-DFEWS) aimed to forecast and predict the occurrence of sediment mass-transport has been developed, based on the characterization of small Alpine catchments (< 50 km2) and the processes that take place in these. The Te-DFWES is based on the identification of predisposing and triggering factors that determinate debris flow occurrence. The Te-DFEWS operates from 2010 in present-time and nowcasting using weather radar observations as input data. Recently (2021), the Te-DFEWS has been improved extending the forecasting window (up to 48h from simulation) by the introduction of Quantitative Precipitation Estimate/Forecast (QPE/QPF) input from COSMO-2I and ICON-IT, local high-resolution weather models. The Te-DFEWS, named DEFENSE (DEbris Flows triggEred by storms - Nowcasting SystEm) and the related warning procedures are presented as an operational tool integrated in the Regional Warning System for Geo-hydrological and Hydraulic Risk at the Functional Centre of Piemonte, managed by the Regional Agency for Environmental Protection of Piemonte (Arpa Piemonte).

Many components in the assembly section of Sodium-cooled Fast Reactor are made of good corrosion-resistant 316 LN Stainless Steel material. To avoid self-welding of the components with the coolant sodium at elevated temperature, hardfacing is inevitable. Ni-based colmonoy-5 is used for hardfacing due to its lower dose rate by Plasma Transferred Arc process due to its low dilution. Since Ni–Cr–B–Si alloy becomes very fluidic while depositing, the major height of the weld overlay rests inside the groove. Hardfacing is also done over the plain surface where grooving is not possible. Therefore, grooved and un-grooved hardfaced specimens were prepared at different travel speeds. Fe content at every 100 μm of the weld overlay was studied by Energy Dispersive Spectroscopy and also the micro hardness was determined at those locations. A correlation between iron dilution from the base metal and the micro hardness was established. Therefore, if the Fe content of the weld overlay is known, the hardness at that location can be obtained using the correlation and vice-versa. A new correlation between micro hardness and dilution coefficient is obtained at different locations. A comparative study between those specimens is carried out to recommend the optimum travel speed for lower dilution. Keywords: Dilution, Hardness, Ni alloy, Austenitic stainless steel, Plasma transferred arc hardfacing (PTAH), Travel speed

Miguel Angel Zapata,1 Dídac Royo-Fibla,1 Octavi Font,1 José Ignacio Vela,2,3 Ivanna Marcantonio,2,3 Eduardo Ulises Moya-Sánchez,4,5 Abraham Sánchez-Pérez,5 Darío Garcia-Gasulla,4 Ulises Cortés,4,6 Eduard Ayguadé,4,6 Jesus Labarta4,6 1Optretina, Barcelona, Spain; 2Ophthalmology Department, Hospital de la Santa Creu I de Sant Pau, Barcelona 08041, Spain; 3Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Barcelona, Spain; 4Barcelona Supercomputing Center (BSC), Barcelona, Spain; 5Universidad Autónoma de Guadalajara - Postgrado en Ciencias Computacionales, Guadalajara, Mexico; 6Universitat Politècnica de Catalunya - BarcelonaTECH, Campus Nord, Barcelona, SpainCorrespondence: Miguel Angel ZapataOptretina, C/ Las Palmas 11, 08195 Sant Cugat del Vallès, Barcelona, SpainTel +34 655809682Email mazapata@optretina.comPurpose: To assess the performance of deep learning algorithms for different tasks in retinal fundus images: (1) detection of retinal fundus images versus optical coherence tomography (OCT) or other images, (2) evaluation of good quality retinal fundus images, (3) distinction between right eye (OD) and left eye (OS) retinal fundus images,(4) detection of age-related macular degeneration (AMD) and (5) detection of referable glaucomatous optic neuropathy (GON).Patients and Methods: Five algorithms were designed. Retrospective study from a database of 306,302 images, Optretina’s tagged dataset. Three different ophthalmologists, all retinal specialists, classified all images. The dataset was split per patient in a training (80%) and testing (20%) splits. Three different CNN architectures were employed, two of which were custom designed to minimize the number of parameters with minimal impact on its accuracy. Main outcome measure was area under the curve (AUC) with accuracy, sensitivity and specificity.Results: Determination of retinal fundus image had AUC of 0.979 with an accuracy of 96% (sensitivity 97.7%, specificity 92.4%). Determination of good quality retinal fundus image had AUC of 0.947, accuracy 91.8% (sensitivity 96.9%, specificity 81.8%). Algorithm for OD/OS had AUC 0.989, accuracy 97.4%. AMD had AUC of 0.936, accuracy 86.3% (sensitivity 90.2% specificity 82.5%), GON had AUC of 0.863, accuracy 80.2% (sensitivity 76.8%, specificity 83.8%).Conclusion: Deep learning algorithms can differentiate a retinal fundus image from other images. Algorithms can evaluate the quality of an image, discriminate between right or left eye and detect the presence of AMD and GON with a high level of accuracy, sensitivity and specificity.Keywords: artificial intelligence, retinal diseases, screening, retinal fundus image

Background: The emergence of oral dryness unrelated to salivary flow volume has always raised many questions over the hypothesis of oral dryness in postmenopausal women. The current research article tries to focus on qualitative changes in saliva in the postmenopausal women suffering from oral dryness. Aim and Objectives: To correlate the severity of oral dryness with qualitative changes in serum estrogen, serum parathyroid (PTH), serum calcium levels in postmenopausal women. Materials and Methodology: This case-control study was carried out on 60 postmenopausal women with 30 forming the case groups as having oral dryness and 30 forming control group without oral dryness. The severity of oral dryness was assessed through the Xerostomia Inventory Score (XI Score). Serum estrogen and serum parathyroid levels were assessed by the ELISA method and serum calcium levels were assessed by Arsenazo III reaction using a semi-autoanalyzer in all participants. Statistical analysis was done by student's t- test and Pearson correlation. Results: Significant differences were observed in the mean values of serum estrogen levels, serum parathyroid levels, and XI score between the case and control groups. (P < 0.001). Serum calcium levels did not show significant variation (P= 0.385) between the groups. The correlation proved that there was an inverse correlation between estrogen levels and XI scores (r-value -0.777). Conclusion: The severity of oral dryness was associated with decreased levels of estrogen and increased levels of parathyroid hormones in postmenopausal women. Fall in estrogen levels is associated with an increase in oral dryness.

The late Hellenistic period is a time of deep entanglement, interconnectedness and complexity. The breakdown of local political systems and the unification of economic spaces had strong repercussions on the perception and expression of several aspects of the cultural identities of local communities. Rapid waves of change can be observed in local religious identities and in the Etruscan sacred landscape: cult buildings were destroyed, sacred places abandoned or replaced by residential areas, and new organisational forms of managing cults appeared; Latin names and new iconographies were given to traditional deities in public religious buildings dedicated to the official religion, while private and popular worshipping polarized around salvation cults. Changes in the sacred landscape regarded both topographic aspects, such as the visibility of cult sites and their connections to settlements, as well as social aspects, such as the patronage of sacred buildings. This paper proposes to employ a relational approach in order to understand changes in the sacred landscape. It analyzes the geographic and social components of the Etruscan sacred landscape by means of Social Network Analysis (SNA), and it does so by looking at the landscape in its entanglement to the archaeological and epigraphic record between 350 and 80 BCE.

Goldenhar syndrome (GS) is a condition with a multitude of abnormalities, classically involving ocular and ear defects, hemifacial microsomia, and vertebral anomalies, which may also be associated with cardiovascular and renal malformations. It is a rare congenital anomaly of unclear etiology. The purpose of reporting this case of a 16-year-old boy with GS is, to update, the existing literature of new oral findings observed.

Bullying has been a recurrent phenomenon throughout the history of education. Among those most vulnerable are those with intellectual disabilities who tend to suffer greater levels of victimisation. The purpose of this research is to analyse the prevalence of bullying of students with intellectual disability in ordinary schools compared to special education schools. The project used a nonexperimental, descriptive and correlational methodology with a sample of 99 students who completed the validated European Bellying Intervention Project Questionnaire measurement tool. The results show that the majority of students who were victimised by bullies left their ordinary school during secondary education. Within ordinary schools, students with disabilities are more likely to experience bullying in the role of victim while in special education schools the most frequent role is that of observer.

Leisure participation enhances the learning of adaptive skills and the quality of life in youth with developmental disabilities. The goal of this study was to evaluate the effects of a leisure education program in individuals with developmental disabilities in terms of adaptive behavior and quality of life. Nine participants divided into two small groups and their families were included. A quasi-experimental design was employed to determine whether there was a program effect. The Adaptive Behavior Assessment System, the KIDSCREEN-27, and the Family Quality of Life Scale were administered before and after the intervention. There was a significant increase in social, home, and school skills as well as a better perception of quality of life in relationships with parents, social support, and school. In addition, the program affected the family's perception of practical and emotional support. Findings provide support for the application of this leisure program to enhance quality of life outcomes.

Research capacity building is a process by which individuals and organizations develop skills and infrastructure resulting in greater ability to conduct useful research. Frequently, research quality and productivity measures focus on outcomes, such as peer-reviewed publications or grants awarded. Such distal measures are not informative when measuring initial stages of research, a common situation in low- and middle-income countries. This study used Cooke's six-principle framework to assess the progress of an autism research collaborative in northern Mexico. We established 64 criteria across the six principles and rated them as Not Started, In Progress, or Achieved, based on narratives and process documentation collected for this purpose. Ratings were established for the years 2018, 2020, and 2022, which correspond to Years 5, 7, and 9 since the beginning of the collaborative, respectively. As of 2022, Principles 2 and 3 ("Close to practice" and "Linkages, collaborations, and partnerships," respectively) had all begun; no criteria were rated as Not started. The principles with the highest Achieved rates were "Linkages, collaborations, and partnerships" (90%), and "Infrastructure" (Principle 6, 70%). Cooke's research capacity building framework is a useful way to monitor progress of research capacity building and contribute to harmonious development of relevant principles at different levels.

Carmen Almansa,1 Christopher S Frampton,2 José Miguel Vela,1 Steve Whitelock,3 Carlos R Plata-Salamán4 1Esteve Pharmaceuticals, S.A., Parc Cientific Barcelona, Barcelona 08028, Spain; 2Rbar3 Ltd, Cambridge, UK; 3Mundipharma Research Ltd, Cambridge, UK; 4Esteve Pharmaceuticals, S.A., Torre Esteve, Barcelona 08038, SpainCorrespondence: Carmen AlmansaEsteve Pharmaceuticals, S.A., Parc Cientific Barcelona, C/Baldiri Reixac 4–8, Barcelona 08028, SpainTel +34 93 446 6148Fax +34 93 446 6432Email calmansa@esteve.comAbstract: Pain is highly prevalent, but frequently untreated or under-treated, and health care professionals are faced with a range of treatment challenges. Multimodal therapy is recommended and can be achieved using open combinations (ie, concomitant administration) of individual agents, fixed-dose combinations (FDCs), or multimodal agents (ie, single agents with multiple mechanisms of action). Co-crystallization of active pharmaceutical ingredients (APIs) offers another approach, with the potential to provide drugs with unique properties and advantages for therapeutic applications compared to combinations. API–API co-crystals are single-entity forms that offer a unique possibility of improving the physicochemical properties of both constituent APIs, as well as permitting their synchronous release. Consequently, this may positively impact on their pharmacokinetic (PK) properties and profiles, providing a potential advantage over FDCs and translating into improved clinical efficacy and safety profiles. We report here a revision of the literature concerning API–API co-crystals for the treatment of pain. It becomes apparent that identifying APIs with complementary mechanisms of action that can be adequately co-crystallized in an appropriate molecular ratio applicable for therapeutic use is challenging. In addition, API–API co-crystals normally result in a mere increased exposure of an API without defined clinical benefits (since, to maintain the benefit-risk, the dose needs to be proportionally reduced to adjust for the increased exposure). An exception to this is the co-crystal of tramadol-celecoxib (CTC), that represents a unique concept in co-crystal technology. In CTC neither of its three active components that have complementary mechanisms of action (ie, the two enantiomers of tramadol and celecoxib) show increased exposure levels versus commercially available single-entity reference products, but rather show a change in their PK profile with potential clinical advantages. CTC is in Phase III clinical development for the treatment of pain.Keywords: co-crystal, efficacy, pain, multimodal, pharmacokinetics, physicochemical properties, safety

Background: Thyroid carcinomas are the most common endocrine tumors – they account for 95% of all endocrine tumors. Thyroid carcinomas are more vascular than normal thyroid tissue. For the tumor to grow and subsequently metastasize it is crucial that it induces angiogenesis. This requires a change in the balance between certain angiogenic factors such as the vascular endothelial growth factor-A (VEGF-A) and the inhibitors of angiogenesis. The aim of this study was to evaluate the role of VEGF-A expression in thyroid carcinomas.

Section 58(1) of the Companies Act 71 of 2008 gives a shareholder the right to appoint a proxy "at any time" for the purpose of participating in, speaking and voting on behalf of that shareholder at a shareholders′ meeting, or providing or withholding written consent on behalf of the shareholder in terms of section 60. One important issue that arises in regard to the appointment of a proxy relates to the proper interpretation of section 58(1) of the Companies Act 71 of 2008, namely whether this section, as read with section 58(3)(c), constitutes an unalterable provision giving a shareholder an unlimited right to appoint a proxy "at any time" before the proxy exercises the shareholder's rights at the shareholders meeting, or whether the time period within which the instrument of a proxy′s appointment must be delivered to the company may be restricted by the MOI. This issue was considered by the SCA in the Richard Du Plessis Barry case in view of the appellant′s contention that the provisions of the MOI that limited the time period within which the instrument appointing a proxy must be delivered to the company, or other person on behalf of the company, were valid. In this note, I examine the Richard Du Plessis Barry case with a focus on the proper interpretation of the right of a shareholder to appoint a proxy "at any time" as conferred by section 58(1) of the Companies Act 71 of 2008. I provide some critical comments on the main issues that this judgement raises, including the interpretation of section 58(1) in the context of "alterable" and "unalterable" provisions of the Companies Act 71 of 2008, a purposive interpretation of section 58(1), the interaction between section 58(1) and section 58(3)(c), the significance of the difference in the wording of section 58(1) of the Companies Act 71 of 2008 and section 189 of the previous Companies Act 61 of 1973, as well as the practical implications of the court's decision in this matter. This is followed by a brief comparative analysis with selected international jurisdictions and some concluding remarks.

Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.