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Abstract Background The incidence of sexually transmitted infections (STIs) is increasing, especially among young people. Tools are needed to increase knowledge about sex education and STI prevention and treatment. Gamification can be a good training tool for both young people and health professionals. The primary objective of this study is to assess the impact of a training intervention on STI prevention, detection, and treatment in primary care professionals. Methods/design Multicentre cluster randomized controlled trial. Groups of primary care professionals will receive an intervention (online video game on sex education and STIs [SEXIT]) and will be compared with control groups that will not receive the intervention. Group assignments will be randomized by clusters. The study will consist of a pre-post evaluation of the intervention: a knowledge test will be administered before and after the intervention and 3 months after the intervention. This test will also be carried out on the same time sequence in the control groups. The impact of the training intervention will be assessed over a 6-month period, focusing on various variables associated with the clinical management of STIs. This evaluation entails the clinical records of diagnostic tests and antibiotic prescriptions related to the clinical approach to STIs. The required sample size is 262 (131 per group). Discussion Compared with those in the control group, improvements in knowledge and clinical behavioural outcomes after the intervention are expected for participants in the intervention groups. We plan to develop an educational video game to increase the knowledge about sexuality, STIs and violence. Protocol registered at ISRCTN with reference number ISRCTN17783607.

In this study, we aimed to assess and compare the prevalence of septate uterus using the diagnostic criteria of the ESHRE-ESGE, ASRM 2016, ASRM 2021, and CUME classifications. This prospective observational study included 977 women of reproductive age. Each participant underwent a transvaginal ultrasound, and a 3D volume of the uterus was obtained for further analysis. Offline assessment of the uterine coronal plane was conducted to measure uterine wall thickness, fundal indentation length, and indentation angle. The diagnosis of a septate uterus was determined according to the criteria of the ESHRE-ESGE, ASRM, and CUME classifications. The prevalence of septate uterus was then calculated and compared across these classifications. The ESHRE-ESGE classification identified 132 women (13.5%) with a septate uterus. The 2016 ASRM classification identified nine women (0.9%), with an additional nine women falling into a grey zone. The 2021 ASRM classification identified fourteen women (1.4%), with eleven women in the grey zone. The CUME classification identified 23 women (2.4%). The prevalence of septate uterus was significantly higher when using the ESHRE-ESGE criteria compared to the 2016 ASRM [relative risk (RR): 7.33 (95% CI: 4.52–11.90)], the 2021 ASRM [RR: 5.28 (95% CI: 3.47–8.02)], and the CUME [RR: 5.94 (95% CI: 3.72–8.86)] (p

This work presents a study of a ventilated hollow core slab system (VHCS) that obviates the need to completely replace the slab of an existing residential building. It is assimilated to a heat exchanger to allow its effectiveness to be studied as a function of the area and airflow rate. The balance between the energy consumed by the fan and the heat evacuated by the system is also studied through the use of the thermo-hydraulic performance factor (THPF), for which a series of cases were simulated by CFD following a methodology in which a configuration is achieved by means of the sequential analysis of cases in which both the thermal effectiveness and the THPF are maximized. The configuration chosen in this study was found to benefit from high airflow rates since, although this implies an increase in fan energy consumption, the increase in heat removed is proportionally greater. It has also been found that the design of the airflow distribution through the slab is of high importance as it affects both the heat exchanged with the slab and the pressure losses. An applicability map has been developed as a function of the temperature of the space below and the air temperature at the inlet of the ventilated roof. The heat flux per unit area that the studied envelope is able to evacuate is about 20 W/m2 K.

Pultruded FRP composites have emerged as a promising alternative to traditional materials like concrete, steel, and timber, especially in corrosive environmental conditions. However, the unique properties of these composites necessitate careful consideration during their implementation, as they differ significantly from conventional materials. Proper testing and characterization of FRP pultruded materials is key for their efficient and safe implementation. However, the existing specifications are not unified, resulting in ambiguity among stakeholders. This paper aims to bridge this gap by thoroughly reviewing current destructive and non-destructive test methods for FRP pultruded materials, specifications, quality control, and health monitoring of FRP structures. Each subsection is further divided into subtopics, providing a comprehensive overview of the subject. By shedding light on these crucial aspects, this article aims to accelerate the adoption and utilization of these innovative materials in practical applications.

Quantitative systems pharmacology (QSP) models and spatial agent-based models (ABM) are powerful and efficient approaches for the analysis of biological systems and for clinical applications. Although QSP models are becoming essential in discovering predictive biomarkers and developing combination therapies through in silico virtual trials, they are inadequate to capture the spatial heterogeneity and randomness that characterize complex biological systems, and specifically the tumor microenvironment. Here, we extend our recently developed spatial QSP (spQSP) model to analyze tumor growth dynamics and its response to immunotherapy at different spatio-temporal scales. In the model, the tumor spatial dynamics is governed by the ABM, coupled to the QSP model, which includes the following compartments: central (blood system), tumor, tumor-draining lymph node, and peripheral (the rest of the organs and tissues). A dynamic recruitment of T cells and myeloid-derived suppressor cells (MDSC) from the QSP central compartment has been implemented as a function of the spatial distribution of cancer cells. The proposed QSP-ABM coupling methodology enables the spQSP model to perform as a coarse-grained model at the whole-tumor scale and as an agent-based model at the regions of interest (ROIs) scale. Thus, we exploit the spQSP model potential to characterize tumor growth, identify T cell hotspots, and perform qualitative and quantitative descriptions of cell density profiles at the invasive front of the tumor. Additionally, we analyze the effects of immunotherapy at both whole-tumor and ROI scales under different tumor growth and immune response conditions. A digital pathology computational analysis of triple-negative breast cancer specimens is used as a guide for modeling the immuno-architecture of the invasive front.

ABSTRACT: Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains unknown. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n=168,287) and non-fatal (13 cohorts, n=27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 100,000 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those estimated from cohorts in high-income countries. Funding: Wellcome Trust (214185/Z/18/Z)

Response to cancer immunotherapies depends on the complex and dynamic interactions between T cell recognition and killing of cancer cells that are counteracted through immunosuppressive pathways in the tumor microenvironment. Therefore, while measurements such as tumor mutational burden provide biomarkers to select patients for immunotherapy, they neither universally predict patient response nor implicate the mechanisms that underlie immunotherapy resistance. Recent advances in single-cell RNA sequencing technology measure cellular heterogeneity within cells of an individual tumor but have yet to realize the promise of predictive oncology. In addition to data, mechanistic multiscale computational models are developed to predict treatment response. Incorporating single-cell data from tumors to parameterize these computational models provides deeper insights into prediction of clinical outcome in individual patients. Here, we integrate whole-exome sequencing and scRNA-seq data from Triple-Negative Breast Cancer patients to model neoantigen burden in tumor cells as input to a spatial Quantitative System Pharmacology model. The model comprises a four-compartmental Quantitative System Pharmacology sub-model to represent a whole patient and a spatial agent-based sub-model to represent tumor volumes at the cellular scale. We use the high-throughput single-cell data to model the role of antigen burden and heterogeneity relative to the tumor microenvironment composition on predicted immunotherapy response. We demonstrate how this integrated modeling and single-cell analysis framework can be used to relate neoantigen heterogeneity to immunotherapy treatment outcomes. Our results demonstrate feasibility of merging single-cell data to initialize cell states in multiscale computational models such as the spQSP for personalized prediction of clinical outcomes to immunotherapy.

Abstract Background Delayed cerebral ischemia (DCI) follows a refractory course in a subgroup of patients with aneurysmal subarachnoid hemorrhage (SAH), leading to diffuse ischemic injury. The role of angiographic vasospasm (AV) is unknown. Our goal is to study the angiographic alterations and the clinical profile of refractory DCI patients. Methods Retrospective study of patients with SAH who presented with DCI treated with medical and endovascular therapy, with a refractory evolution, defined as multiple ischemic infarction and brain death. Results Out of a cohort of 336 patients, 7 (2%) developed refractory DCI. The median age of the patients was 48 (38–60) years old. Five patients had ruptured anterior communicating artery (ACoA) aneurysms. Four patients were treated with coil embolization, and three with microsurgical clipping. Angiographic vasospasm was classified as severe in 5 cases. Compromise of bilateral circulation was detected in six patients. Distal circulation vasospasm occurred in five cases. Slow circulatory transit times were observed in three patients. Conclusion Angiographic findings such as bilateral circulatory compromise and distal vasospasm were frequent alterations. Further studies are required to establish the association of these findings with the clinical outcomes.

Increased traffic in combination with growing environmental impacts have led to the accelerated degradation of built infrastructure. In reinforced concrete structures, the corrosion of steel reinforcement is the predominant cause of deterioration. Thus, over the last years the use of glass fiber reinforced polymer (GFRP) composites as internal reinforcement bars (rebars) for concrete structures has been evaluated, and has been proved to be a viable alternative to traditional steel reinforcement mainly due to its tensile strength and non-corrosive nature. However, thus far, the GFRP rebar market is diverse and manufacturers around the world produce GFRP rebar types with different surface enhancements to improve the bond to concrete characteristics. In this study, the bond performance of three dissimilar GFRP rebar types (sand coated, helically grooved and with surface lugs) was evaluated over time in seawater environments, with a focus on the bond strength. Accordingly, specimens were exposed to seawater in circulating chambers at three different temperatures (23 °C, 40 °C and 60 °C) for multiple time periods (60 and 120 days). To evaluate the bond performance, pullout tests were conducted according to ASTM D7913. The results showed that the bond strength varied with the surface enhancement features. However, the bond strength did not vary significantly with exposure time and temperature for all three evaluated rebar types.

Abstract Background Poor quality of life in adults with anorexia nervosa (AN) and persistent high rates of readmission highlight the necessity of developing interventions to optimize treatment outcomes. ECHOMANTRA is a novel online intervention based on interventions for carers (Experienced Carers Helping Others, ECHO) and patients (Maudsley Model of Anorexia Nervosa Treatment for Adults, MANTRA) with anorexia nervosa. The objective of this paper is to describe the study protocol of a randomized control trial (RCT) aimed at evaluating the efficacy of an adaptation of the ECHOMANTRA for adults AN inpatients and outpatients, and their carers, to be implemented as an add-on to treatment-as-usual (TAU). Methods In a multi − center pilot randomized controlled trial (RCT), 148 adult AN patients, and their carers, will be randomized to receive treatment as usual (TAU) or TAU plus ECHOMANTRA. Assessments will take place at baseline (T0), post-intervention (2-month) (T1), 6-month follow-up (T2), and 12-month follow-up (T3). Primary outcomes will be eating disorder psychopathology and psychological well-being. For carers, outcome variables will include psychological well-being, accommodation and enabling behaviors, expressed emotion, illness burden, quality of life and care skills. Discussion This study will provide evidence of the efficacy of this novel, online and protocolized intervention in facilitating the recovery of these patients. Trial registration ISRCTN registry (Identifier: 80253157 https://doi.org/10.1186/ISRCTN80253157 ).

Eating disorders have serious physical, mental and social consequences that can affect the quality of life of the sufferer. This study aimed to evaluate the relationship between the severity of ED-related psychopathology and clinical impairment in adolescents with anorexia nervosa (AN) as well as their perception of health-related quality of life. Eighty-six Spanish young women with AN completed a set of questionnaires assessing eating disorder pathology, clinical impairment, and quality of life. The set included the following instruments: the Eating Disorder Examination Questionnaire, Clinical Impairment Assessment, Short Form-12 Item Health Survey, and the Eating Disorder-Specific Heath-Related Quality of Life instrument. Descriptive and regression analyses were applied to identify associations between variables. Higher scores on clinical impairment domains were associated with greater impairment of mental and physical health. Moreover, clinical impairment domains and concerns due to ED were related to a lower quality of life. In conclusion, adolescents with AN have a poor quality of life. Moreover, the findings suggest that the clinical features of impairment may serve as severity indicators of quality of life.

The article aims to provide an analysis based on the practical experience of social intervention in violence prevention with migrant minors arriving alone in Spain. In order to offer keys and recommendations, and based on situated knowledge, we provide insights on how to approach the intervention framework from a methodological point of view using liminal spaces as border and transition places that need to be named and taken into consideration for a transformative work. Different metaphorical borders, characterized by tension and potential change, are analyzed from a gender and intersectional perspective. We discuss the Law-border and the tension between protection they receive as minors and exclusion/politics of suspicion they receive as migrants. The Age-border (children/men) is discussed taking into account the different gender regimes they cross. The Color-border: here issues of racism and colonialism are considered. Finally, we discuss the Masculinity-border and the tension between reception and the reproduction of violence. We use the concept of liminal masculinities as a specific state or form that subordinate or marginalized masculinity adopts in migrant minors, suspended legally, functionally, and biographically, among others borders.