Experimental Study of Tuberculosis: From Animal Models to Complex Cell Systems and Organoids

We acknowledge financial support of the Humane Society International (HIS), Humane Society of the United States (HSUS), and from the Portuguese Foundation for Science and Technology (FCT) for providing a PhD grant to KLF (SFRH/BD/114405/2016). The MS lab is financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 -Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01-0145-FEDER-007274). MS is a FCT Associate Investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Tuberculosis (TB) is a devastating disease to mankind that has killed more people than any other infectious disease. Despite many efforts and successes from the scientific and health communities, the prospect of TB elimination remains distant. On the one hand, sustainable public health programs with affordable and broad implementation of anti-TB measures are needed. On the other hand, achieving TB elimination requires critical advances in three areas: vaccination, diagnosis, and treatment. It is also well accepted that succeeding in advancing these areas requires a deeper knowledge of host-pathogen interactions during infection, and for that, better experimental models are needed. Here, we review the potential and limitations of different experimental approaches used in TB research, focusing on animal and human-based cell culture models. We highlight the most recent advances in developing in vitro 3D models and introduce the potential of lung organoids as a new tool to study Mycobacterium tuberculosis infection

Novel 3D compression methods for geometry, connectivity and texture

A large number of applications in medical visualization, games, engineering design, entertainment, heritage, e-commerce and so on require the transmission of 3D models over the Internet or over local networks. 3D data compression is an important requirement for fast data storage, access and transmission within bandwidth limitations. The Wavefront OBJ (object) file format is commonly used to share models due to its clear simple design. Normally each OBJ file contains a large amount of data (e.g. vertices and triangulated faces, normals, texture coordinates and other parameters) describing the mesh surface. In this paper we introduce a new method to compress geometry, connectivity and texture coordinates by a novel Geometry Minimization Algorithm (GM-Algorithm) in connection with arithmetic coding. First, each vertex (x, y, z) coordinates are encoded to a single value by the GM-Algorithm. Second, triangle faces are encoded by computing the differences between two adjacent vertex locations, which are compressed by arithmetic coding together with texture coordinates. We demonstrate the method on large data sets achieving compression ratios between 87%—99% without reduction in the number of reconstructed vertices and triangle faces. The decompression step is based on a Parallel Fast Matching Search Algorithm (Parallel-FMS) to recover the structure of the 3D mesh. A comparative analysis of compression ratios is provided with a number of commonly used 3D file formats such as VRML, OpenCTM and STL highlighting the performance and effectiveness of the proposed method

EULAR COVID-19 registry: lessons learnt and future considerations.

Future disease outbreaks of epidemic proportion are inevitable. Advance planning and preparation is essential to mitigate future public health risks; the WHO emphasises the importance of in-depth evaluation of response to and lessons learnt from a national/international pandemic.1 Research is critical to an informed, evidence-based response, therefore establishing pandemic research study protocols, systems to manage and report data, and rapid response teams are considered key to well-prepared, accelerated research in public health emergencies.2 Establishing international data collection registries poses many challenges, which are only amplified in the urgent nature of a global pandemic. The aim of this manuscript is to reflect on the successes and challenges of the European Alliance of Associations for Rheumatology (EULAR) COVID-19 registry3 to better understand how the rheumatology community (and other disease-specific communities) can be better prepared for rapid response research in the future. In particular, we consider the successes and challenges of the registry, what can be learnt from this experience, and what procedures and resources should be established and strengthened now in preparation for future pandemics

A tool for routine monitoring and feedback of morbidities following paediatric cardiac surgery

Short-term survival after paediatric cardiac surgery has improved significantly over the past 20 years and increasing attention is being given to measuring and reducing incidence of morbidities following surgery. How to best use routinely collected data to share morbidity information constitutes a challenge for clinical teams interested in analysing their outcomes for quality improvement. We aimed to develop a tool facilitating this process in the context of monitoring morbidities following paediatric cardiac surgery, as part of a prospective multi-centre research study in the United Kingdom. We developed a prototype software tool to analyse and present data about morbidities associated with cardiac surgery in children. We used an iterative process, involving engagement with potential users, tool design and implementation, and feedback collection. Graphical data displays were based on the use of icons and graphs designed in collaboration with clinicians. Our tool enables automatic creation of graphical summaries, displayed as a Microsoft PowerPoint presentation, from a spreadsheet containing patient-level data about specified cardiac surgery morbidities. Data summaries include numbers/percentages of cases with morbidities reported, co-occurrences of different morbidities, and time series of each complication over a time window. Our work was characterised by a very high level of interaction with potential users of the tool, enabling us to promptly account for feedback and suggestions from clinicians and data managers. The United Kingdom centres involved in the project received the tool positively, and several expressed their interest in using it as part of their routine practice

Factors associated with unplanned reinterventions and their relation to early mortality after pediatric cardiac surgery

Objective: Unplanned reintervention (uRE) is used as an indicator of patient morbidity and quality of care in pediatric cardiac surgery. We investigated associated factors and early mortality after uREs. / Methods: Morbidity data were prospectively collected in 5 UK centers between 2015 and 2017; uRE included surgical cardiac, interventional transcatheter cardiac, permanent pacemaker, and diaphragm plication procedures. Mortality (30-day and 6-month) in uRE/no-uRE patients was reported before and after matching. Predicted 30-day mortality was calculated using the Partial Risk Adjustment in Surgery score. / Results: A total of 3090 procedures (2861 patients) were included (median age, 228 days). There were 146 uREs, resulting in an uRE rate of 4.7%. Partial Risk Adjustment in Surgery score, 30-day mortality and 6-month mortality in uRE and no-uRE groups were 2.4% versus 1.3%, 8.9% versus 1%, and 17.1% versus 2.4%, respectively. After matching, mortality at 6 months remained higher in uRE compared with no-uRE (12.2% vs 1.4%; P = .02; 74 pairs). In the uRE group, 21 out of 25 deaths at 6 months occurred when at least 1 additional postoperative complication was present. In multivariable analysis, neonatal age (P = .002), low weight (P = .009), univentricular heart (P < .001), and arterial shunt (P < .001) were associated with increased risk of uRE, but Partial Risk Adjustment in Surgery score was not (only in univariable analysis). / Conclusions: uREs are a relatively frequent complication after pediatric cardiac surgery and are associated with some patient characteristics, but not the Partial Risk Adjustment in Surgery risk score. Early mortality was higher after uRE, independent of preoperative factors, but linked to other postoperative complications

Oportunidades perdidas na prevenção da sífilis congênita e da transmissão vertical do HIV

OBJECTIVE: To estimate the prevalence of missed opportunities for congenital syphilis and HIV prevention in pregnant women who had access to prenatal care and to assess factors associated to non-testing of these infections. METHODS: Cross-sectional study comprising a randomly selected sample of 2,145 puerperal women who were admitted in maternity hospitals for delivery or curettage and had attended at least one prenatal care visit, in Brazil between 1999 and 2000. No syphilis and/or anti-HIV testing during pregnancy was a marker for missed prevention opportunity. Women who were not tested for either or both were compared to those who had at least one syphilis and one anti-HIV testing performed during pregnancy (reference category). The prevalence of missed prevention opportunity was estimated for each category with 95% confidence intervals. Factors independently associated with missed prevention opportunity were assessed through multinomial logistic regression. RESULTS: The prevalence of missed prevention opportunity for syphilis or anti-HIV was 41.2% and 56.0%, respectively. The multivariate analysis showed that race/skin color (non-white), schooling (OBJETIVO: Estimar la prevalencia de oportunidad de pérdida de prevención de la sífilis y el HIV entre gestantes que tuvieron acceso al pre-natal y factores asociados con la no evaluación de estos agravios. MÉTODOS: Se realizó estudio transversal con muestra aleatoria de 2.145 puérperas de Brasil, 1999 y 2000 admitidas en maternidades para parto o curetaje y que habían realizado al menos una consulta de pre-natal. La no realización del examen de prueba para sífilis y/o anti-HIV durante el embarazo fue usada como marcador para oportunidad de pérdida de prevención. Las mujeres que realizaron sólo examen de sífilis o sólo examen de anti-HIV, o que no realizaron ninguno, fueron comparadas con las que realizaron los dos (categoría de referencia). La prevalencia de oportunidad de pérdida de prevención fue estimada para cada categoría, con intervalo de confianza de 95%. Los factores asociados con la oportunidad de pérdida de prevención fueron analizados por medio de regresión logística multinomial. RESULTADOS: La prevalencia de oportunidad de pérdida de prevención para la realización de la prueba de sífilis o anti-HIV fue de 41,2% e 56,0%, respectivamente. El análisis multivariado indicó que raza/color (no blanca), escolaridad (< 8 años de estudio), estado civil (soltera), renta < 3 salarios mínimos, relación sexual durante el embarazo, no haber tenido sífilis anterior al embarazo actual, realización de seis o mas consultas de pre-natal y la realización de la última visita antes del tercer trimestre de embarazo, estaban asociados con mayor riesgo de tener oportunidad de pérdida de prevención. Se observó una asociación negativa entre estado civil (soltera), lugar de realización de pre-natal (hospital) y la realización de la primera consulta pre-natal en el tercer trimestre con oportunidad de pérdida de prevención. CONCLUSIONES: Altos porcentajes de gestantes no evaluadas señalan fallas en la prevención y control de la infección por HIV y de la sífilis congénita en los servicios de salud. Las gestantes continúan interrumpiendo el cuidado pre-natal precozmente y no logran realizar los procedimientos de selección para HIV y sífilis.OBJETIVO: Estimar a prevalência de oportunidade perdida de prevenção a sífilis e HIV entre gestantes que tiveram acesso ao pré-natal e fatores associados a não-testagem para esses agravos. MÉTODOS: Estudo transversal com amostra aleatória de 2.145 puérperas do Brasil, 1999 e 2000 admitidas em maternidades para parto ou curetagem e que haviam realizado pelo menos uma consulta de pré-natal. A não-realização de exame de teste para sífilis e/ou anti-HIV durante a gravidez foi usada como marcador para oportunidade perdida de prevenção. Mulheres que realizaram apenas exame de sífilis ou apenas o anti-HIV, ou não realizaram nenhum, foram comparadas àquelas que realizaram os dois (categoria de referência). A prevalência de oportunidade perdida de prevenção foi estimada para cada categoria, com intervalo de confiança de 95%. Os fatores associados com oportunidade perdida de prevenção foram analisados por meio de regressão logística multinomial. RESULTADOS: A prevalência de oportunidade perdida de prevenção para a realização do teste de sífilis ou anti-HIV foi de 41,2% e 56,0%, respectivamente. A análise multivariada indicou que raça/cor (não branca), escolaridade (< 8 anos de estudo), estado civil (solteira), rend

Definition of important early morbidities related to paediatric cardiac surgery

BACKGROUND: Morbidity is defined as a state of being unhealthy or of experiencing an aspect of health that is "generally bad for you", and postoperative morbidity linked to paediatric cardiac surgery encompasses a range of conditions that may impact the patient and are potential targets for quality assurance. METHODS: As part of a wider study, a multi-disciplinary group of professionals aimed to define a list of morbidities linked to paediatric cardiac surgery that was prioritised by a panel reflecting the views of both professionals from a range of disciplines and settings as well as parents and patients. RESULTS: We present a set of definitions of morbidity for use in routine audit after paediatric cardiac surgery. These morbidities are ranked in priority order as acute neurological event, unplanned re-operation, feeding problems, the need for renal support, major adverse cardiac events or never events, extracorporeal life support, necrotising enterocolitis, surgical site of blood stream infection, and prolonged pleural effusion or chylothorax. It is recognised that more than one such morbidity may arise in the same patient and these are referred to as multiple morbidities, except in the case of extracorporeal life support, which is a stand-alone constellation of morbidity. CONCLUSIONS: It is feasible to define a range of paediatric cardiac surgical morbidities for use in routine audit that reflects the priorities of both professionals and parents. The impact of these morbidities on the patient and family will be explored prospectively as part of a wider ongoing, multi-centre study

Farm management factors associated with bulk tank somatic cell count in Irish dairy herds

The relationship between bulk tank somatic cell count (SCC) and farm management and infrastructure was examined using data from 398 randomly selected, yet representative, Irish dairy farms where the basal diet is grazed grass. Median bulk tank SCC for the farms was 282,887 cells/ml ranging from 82,209 to 773,028 cells/ml. Two questionnaires were administered through face-to-face contact with each farmer. Herd-level factors associated with bulk tank SCC were determined using linear models with annual somatic cell score (i.e., arithmetic mean of the natural logarithm of bulk tank SCC) included as the dependent variable. All herd level factors were analysed individually in separate regression models, which included an adjustment for geographical location of the farm; a multiple regression model was subsequently developed. Management practices associated with low SCC included the use of dry cow therapy, participation in a milk recording scheme and the use of teat disinfection post-milking. There was an association between low SCC and an increased level of hygiene and frequency of cleaning of the holding yard, passageways and cubicles. Herd management factors associated with bulk tank SCC in Irish grazing herds are generally in agreement with most previous studies from confinement systems of milk production