Colour perception develops throughout childhood with increased risk of deficiencies in children born prematurely.

AIM: To quantify the impact of prematurity on chromatic discrimination throughout childhood, from 2 to 15 years of age. METHODS: We recruited two cohorts of children, as part of the TrackAI Project, an international project with seven different study sites: a control group of full-term children with normal visual development and a group of children born prematurely. All children underwent a complete ophthalmological exam and an assessment of colour discrimination along the three colour axes: deutan, protan and trytan using a DIVE device with eye tracking technology. RESULTS: We enrolled a total of 1872 children (928 females and 944 males) with a mean age of 6.64 years. Out of them, 374 were children born prematurely and 1498 were full-term controls. Using data from all the children born at term, reference normative curves were plotted for colour discrimination in every colour axis. Pre-term children presented worse colour discrimination than full-term in the three colour axes (p < 0.001). Even after removing from the comparison, all pre-term children with any visual disorder colour discrimination outcomes remained significantly worse than those from full-term children. CONCLUSION: While colour perception develops throughout the first years of life, children born pre-term face an increased risk for colour vision deficiencies.

Experiences of Mothers of Preterm Infants in the Neonatal Intensive Care Unit During the COVID-19 Pandemic.

BACKGROUND: The neonatal intensive care unit (NICU) stay following the birth of a preterm infant can be stressful and traumatic for families. During the COVID-19 pandemic, the NICU environment changed precipitously as infection control and visitor restriction measures were implemented. PURPOSE: Our study aimed to examine the impact of the pandemic policies on the experiences of mothers of preterm infants during their stay in the NICU. METHODS: Semistructured interviews were conducted with mothers of preterm infants hospitalized in a Canadian tertiary-level NICU. Informed by interpretive description methodology, interview content was transcribed and analyzed using a thematic analysis approach. The identified themes were validated, clarified, or refined using investigator triangulation. RESULTS: Nine English-speaking mothers, aged 28 to 40 years, were interviewed. Four themes emerged from the analysis of their experiences: (1) disrupted family dynamic, support, and bonding; (2) physical and emotional isolation; (3) negative psychological impact compounded by added concerns, maternal role change, and survival mode mentality; and (4) positive aspects of the pandemic management measures. IMPLICATIONS FOR PRACTICE: During the pandemic, the way that care was provided in the NICU changed. This study helps to explore how neonatal clinicians can foster individual and organizational resilience to keep patients and families at the center of care, even when the healthcare system is under intense stress. IMPLICATIONS FOR RESEARCH: : Our results show that these changes heightened mothers' distress, but also had a modest positive impact. Further research about long-term consequences of pandemic policies on the mother and preterm infant after NICU discharge is warranted.

Development of oculomotor control throughout childhood: A multicenter and multiethnic study.

Although steady fixation is a key aspect of a proper visual function, it is only subjectively assessed in young and uncooperative children. In the present study, we characterize the development of fixational behavior throughout childhood in a large group of healthy children 5 months of age and up, recruited in five geographically diverse sites. In order to do it, we examined 802 healthy children from April 2019 to February 2020. Their oculomotor behavior was analyzed by means of an automated digital system, based on eye-tracking technology. Oculomotor outcomes were gaze stability, fixation stability and duration of fixations (for both long and short fixational tasks), and saccadic reaction time. Ninety-nine percent of all recruited children were successfully examined. Fixational and saccadic performance improved with age throughout childhood, with more pronounced changes during the first 2 years of life. Gaze and fixation tended to be more stable with age (p < 0.001 for most the outcomes), and saccades tended to be faster. In a multivariate analysis, including age and ethnicity as independent variables and adjusting by data quality, age was related with most fixational outcomes. Our automated digital system and eye-tracking data allow us to quantitatively describe the development of oculomotor control during childhood, assess visual fixation and saccadic performance in children 5 months of age and up, and provide a normative reference of fixational outcomes for clinical practice.

Rare immunofluorescence patterns of autoantibodies on HEp-2 cells defined by ICAP identify different autoimmune diseases in the absence of associated specificities: a Spanish multicentre study.

OBJECTIVES: ANA are the most extensively used test for the diagnosis of systemic autoimmune diseases. However, testing by indirect immunofluorescence assays (IIFAs) on HEp-2 cells, the gold standard test, is time-consuming and needs expertise. Thus there is a trend to replace it with other automated solid-phase assays directed against specific ANA. Nonetheless, the Hep-2 cell is an autoantigen array and ANA have been classified into 29 types, some of them with no clear association with a specificity to be detected. It is especially in these uncommon patterns where no clinical relationship is found and no antigenic specificity is detected. Here we retrospectively collected clinical data from patients with confirmed uncommon HEp-2 IIFA patterns to search for an associated clinical condition. METHODS: We conducted an observational retrospective study including 608 patients with organ-specific and non-organ-specific autoimmune diseases (OSADs and NOSADs, respectively) with a confirmed rare pattern of ANA detected by IIFA on HEp-2 cells in the routine practice of the Spanish European Autoantibodies Standardization Initiative laboratories. Inclusion criteria are the existence of a minimum follow-up of 2 years and the availability of clinical data. RESULTS: Nuclear patterns were more frequent in SLE (P = 0.001) and SS (P = 0.001), whereas the cytoplasmic ones were significantly higher in SSc (P = 0.022) and inflammatory myositis (P = 0.016). Mitotic patterns did not show any preferences for a specific disease and 62.7% of them corresponded to the nuclear mitotic apparatus pattern (AC-26). The most frequent NOSADs in patients with the AC-26 pattern were SLE (28.6%), SS (11.9%) and RA (11.9%). The cytoplasmic HEp-2 IIFA patterns were equally distributed in both groups of patients. In the OSAD patients there was no predominant pattern, except for AC-6 in primary biliary cholangitis due to Sp-100 antibodies (P < 0.001). CONCLUSION: Detection of infrequent ANA might be a unique finding with no disease-associated specificities and could lead to the suspicion of an autoimmune disease.

Oculomotor deficits in children adopted from Eastern Europe.

AIM: We aim to assess oculomotor behaviour in children adopted from Eastern Europe, who are at high risk of maternal alcohol consumption. METHODS: This cross-sectional study included 29 adoptees and 29 age-matched controls. All of them underwent a complete ophthalmological examination. Oculomotor control, including fixation and saccadic performance, was assessed using a DIVE device, with eye tracking technology. Anthropometric and facial measurements were obtained from all the adopted children, to identify features of foetal alcohol spectrum disorders (FASD). Fixational and saccadic outcomes were compared between groups, and the effect of adoption and FASD features quantified. RESULTS: Oculomotor performance was poorer in adopted children. They presented shorter (0.53 vs 1.43 milliseconds in the long task and 0.43 vs 0.82 in the short task) and more unstable fixations (with a bivariate contour ellipse area of 27.9 vs 11.6 degree2 during the long task and 6.9 vs 1.3 degree2 during the short task) and slower saccadic reactions (278 vs 197 milliseconds). Children with sentinel finding for FASD showed the worst oculomotor outcomes. CONCLUSION: Children adopted from Eastern Europe present oculomotor deficits, affecting both fixation and saccadic skills. We highlight prenatal exposure to alcohol as the main cause for these deficits.

Visual cognitive impairments in children at risk of prenatal alcohol exposure.

AIM: To evaluate the relationship between visoperception and anthropometric features related to prenatal alcohol exposure. METHODS: We compared two cohorts of infants aged between 5 and 18 years. Seventy-nine children, adopted from Eastern Europe, were included in the study group. The control group was formed by age and gender matched children born in Spain. All children underwent a full ophthalmologic assessment and standardised testing of visual cognitive skills. RESULTS: Adoptees presented worse visual motor and visual perceptual outcomes in all skills compared with control subjects, with statistically significant difference in test of visual perceptual skills (TVPS) global centile (50.3 vs 66.8; P = 0.001), spatial relationships (64.6 vs 81.9; P = 0.004) and visual figure-ground (52.1 vs 74.1; P = 0.002) tasks. Face recognition was as well significantly worse in adopted children (42.4 vs 57.1; P = 0.009). Twenty-one adopted children (26.6%) had sentinel finding for foetal alcohol spectrum disorders (FASD). Main facial features related to FASD correlated with visual cognitive outcomes. Of the adopted children, those diagnosed of FASD showed incrementally worse visual perceptual and visual motor outcomes (TVPS global centile = 36.86, P = 0.001; TVAS = 10.38, P = 0.002). CONCLUSION: Children adopted from eastern Europe are at increased risk of visual perceptual disabilities, especially those with sentinel findings of foetal alcohol syndrome disorders.

Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes.

PURPOSE: To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administration in rabbit eyes. METHODS: Thirty-two New Zealand albino rabbits were divided into two experimental groups to test intravitreal (IVT group) and suprachoroidal (SCS group) administration of a 100-µl and 50-µl Laponite suspension respectively. Following injection, the eyes were monitored by ocular tonometry, slit-lamp eye examination and indirect ophthalmoscopy, at 24 h, 1, 4, 12, and 14 weeks post administration. Histological examination was also performed to determine whether any ocular pathological change had occurred. Throughout the study, LAP presence in vitreous was estimated by complexometric titration with ethylenediaminetetraacetic acid (EDTA), taking advantage of the Laponite high content of magnesium ions. RESULTS: Neither significant differences in the intraocular pressure, nor relevant ocular complications were found in the two experimental groups after LAP administration. The histology of the retina remained unchanged. LAP presence in vitreous could be indirectly confirmed by complexometric titration until 14 weeks post administration in eyes of IVT group. CONCLUSION: Laponite could be considered as a vehicle for potential clinical use in ocular drug administration, due to its proven ocular biocompatibility and its transparency in gel state.

The brain frequency tuning function for facial emotion discrimination: An ssVEP study.

Steady-state visual evoked potentials have only been applied recently to the study of face perception. We used this method to study the spatial and temporal dynamics of expression perception in the human brain and test the prediction that, as in the case of identity perception, the optimal frequency for facial expression would also be in the range of 5-6 Hz. We presented facial expressions at different flickering frequencies (2-8 Hz) to human observers while recording their brain electrical activity. Our modified adaptation paradigm contrasted blocks with varying expressions versus blocks with a constant neutral expression, while facial identity was kept constant. The presentation of different expressions created a larger steady-state response only at 5 Hz, corresponding to a cycle of 200 ms, over right occipito-temporal electrodes. Source localization using a time-domain analysis showed that the effect localized to the right occipito-temporal cortex, including the superior temporal sulcus and fusiform gyrus.

Interactions between the perception of age and ethnicity in faces: an event-related potential study.

Face perception models propose that different facial attributes are processed by anatomically distinct neural pathways that partially overlap. Whether these attributes interact functionally is an open question. Our goal was to determine if there are interactions between age and ethnicity processing and, if so, at what temporal epoch these interactions are evident. We monitored event-related potentials on electroencephalography while subjects categorized faces by age or ethnicity in two conditions: a baseline in which the other of these two properties not being categorized was held constant and an interference condition in which it also varied, as modelled after the Garner interference paradigm. We found that, when participants were categorizing faces by age, variations in ethnicity increased the amplitude of the right face-selective N170 component. When subjects were categorizing faces by ethnicity, variations in age did not alter the N170. We concluded that there is an asymmetric pattern of influence between age and ethnicity on early face-specific stages of visual processing, which has parallels with behavioural evidence of asymmetric interactions between identity and expression processing of faces.

Temporal dynamics of the face familiarity effect: bootstrap analysis of single-subject event-related potential data.

Prior event-related potential studies using group statistics within a priori selected time windows have yielded conflicting results about familiarity effects in face processing. Our goal was to evaluate the temporal dynamics of the familiarity effect at all time points at the single-subject level. Ten subjects were shown faces of anonymous people or celebrities. Individual results were analysed using a point-by-point bootstrap analysis. While familiarity effects were less consistent at later epochs, all subjects showed them between 130 and 195 ms in occipitotemporal electrodes. However, the relation between the time course of familiarity effects and the peak latency of the N170 was variable. We concluded that familiarity effects between 130 and 195 ms are robust and can be shown in single subjects. The variability of their relation to the timing of the N170 potential may lead to underestimation of familiarity effects in studies that use group-based statistics.

Celiac disease and HLA-DQ genotype: diagnosis of different genetic risk profiles related to the age in Badajoz, southwestern Spain.

BACKGROUND AND OBJECTIVES: celiac disease is associated with the HLA class II alleles: DQA1*05-DQB1*02 and DQB1*0302. The genetic risk for celiac disease may depend on the presence or absence of such alleles, their combination or number of copies. This study aimed to establish the differences in HLA genotypes between celiac patients diagnosed during childhood and adulthood, and between patients and healthy controls, and to determine the risk of disease in each genotypic category. METHODS: we classified 350 celiac patients at time of diagnosis and 218 controls into 14 categories according to their HLA genotype, based on the presence or absence of risk alleles. RESULTS: we found statistically significant differences between the genotype frequencies of celiac patients diagnosed as being children and adults. DQA1*05 (x 1 copy), DQB1*02 (x 1 copy), DQB1*0302 (x 0 copies) was the most frequent genotype in individuals diagnosed in childhood, whereas DQA1*05 (x 1 copy), DQB1*02 (x 2 copies), DQB1*0302 (x 0 copies) was the most frequent in adults. The risk for disease in each genotypic category in celiac children and adults turned out to be different. The presence of DQB1*0302 did not increase risk in children, but did in adults. CONCLUSION: in our celiac population, we found a different genetic pattern according to age of diagnosis. That could suggest that the pathogenic mechanism of the disease is not exactly the same in both age groups, which could somehow determine clinical presentation of the disease, its epidemiology, coexisting diseases, and complications.

A steady-state visual evoked potential approach to individual face perception: effect of inversion, contrast-reversal and temporal dynamics.

Presentation of a face stimulus for several seconds at a periodic frequency rate leads to a right occipito-temporal evoked steady-state visual potential (SSVEP) confined to the stimulation frequency band. According to recent evidence (Rossion and Boremanse, 2011), this face-related SSVEP is largely reduced in amplitude when the exact same face is repeated at every stimulation cycle as compared to the presentation of different individual faces. Here this SSVEP individual face repetition effect was tested in 20 participants stimulated with faces at a 4 Hz rate for 84 s, in 4 conditions: faces upright or inverted, normal or contrast-reversed (2×2 design). To study the temporal dynamics of this effect, all stimulation sequences started with 15s of identical faces, after which, in half of the sequences, different faces were introduced. A larger response to different than identical faces at the fundamental (4 Hz) and second harmonic (8 Hz) components was observed for upright faces over the right occipito-temporal cortex. Weaker effects were found for inverted and contrast-reversed faces, two stimulus manipulations that are known to greatly affect the perception of facial identity. Addition of the two manipulations further decreased the effect. The phase of the fundamental frequency SSVEP response was delayed for inverted and contrast-reversed faces, to the same extent as the latency delay observed at the peak of the face-sensitive N170 component observed at stimulation sequence onset. Time-course analysis of the entire sequence of stimulation showed an immediate increase of 4Hz amplitude at the onset (16th second) of different face presentation, indicating a fast, large and frequency-specific release to individual face adaptation in the human brain. Altogether, these observations increase our understanding of the characteristics of the human steady-state face potential response and provide further support for the interest of this approach in the study of the neurofunctional mechanisms of face perception.

[The regulation of structural telework in Iberoamérica]. / La regulación del teletrabajo estructural en Iberoamérica.

The pandemic occasioned by COVID-19 has caused, as a sudden and unpredictable need, the introduction of teleworking in the productive systems of most of the countries. Many States have had to resort to old and outdated norms that did not assume the few guarantees of the existing international and supranational instruments. However, other countries have taken advantage of the health emergency situation to reform and update their telework regulations. The purpose of this contribution is to analyze the new regulations that emerged during the pandemic and to carry out a general assessment of their contents to check if they are adapted to the demands and recommendations that, in a digital society, should characterize teleworking. The purpose of this contribution is to analyze the new rules that have arisen from the pandemic and to make a general assessment of their contents to check whether they are adapted to the requirements and recommendations that, in a digital society, should characterize teleworking. To do this we make a tour of the international legal system in order to identify the instruments, rules and principles that can help us to outline the basic institutions that should support the regulation of telework to, then, make an assessment of the laws that in recent months have been implemented in some of the countries that make up the Ibero-American space (Argentina, Bolivia, Chile, Colombia, Costa Rica, Spain, El Salvador, Mexico, Peru, Portugal) to deal with this reality.  The analysis carried out shows that, even with few international references, the different legal systems have been able to articulate guaranteeing regulations that observe the few existing guidelines: voluntariness, reversibility, and an important set of rights for teleworkers. However, there are pending issues that need to be addressed in greater depth: those related to the right to occupational health and digital rights, as well as the development of the institution through collective bargaining, a mechanism that could balance the different interests and ensure a greater acceptance of these regulations.

La pandemia originada por la COVID-19 ha provocado, como necesidad súbita e imprevisible, la implantación del teletrabajo en los sistemas productivos de la generalidad de los países. Muchos Estados han tenido que recurrir a normas antiguas y desfasadas que no asumían las pocas garantías de los instrumentos internacionales y supranacionales existentes. Sin embargo, otros países han aprovechado la situación de emergencia sanitaria para reformar y actualizar sus normas de teletrabajo.  La presente contribución tiene por objeto analizar las nuevas normas surgidas con ocasión de la pandemia y efectuar una valoración general de sus contenidos para comprobar si se adaptan a las exigencias y recomendaciones que, en una sociedad digital, deben caracterizar al teletrabajo. Para ello hacemos un recorrido por el ordenamiento internacional con la finalidad de identificar los instrumentos, reglas y principios que nos puedan ayudar a perfilar las instituciones básicas que deben sostener la regulación del teletrabajo para, seguidamente, hacer una valoración de las legislaciones que en los últimos meses se han implantado en algunos de los países que integran el espacio iberoamericano (Argentina, Bolivia, Chile, Colombia, Costa Rica, España, El Salvador, México, Perú, Portugal) para hacer frente a esta realidad.  El análisis efectuado evidencia que, aún con escasos referentes internacionales, los distintos ordenamientos han sabido articular regulaciones garantistas que observan las pocas directrices existentes: voluntariedad, reversibilidad y un conjunto importante de derechos para las personas teletrabajadoras. No obstante, existen cuestiones pendientes que deben ser abordadas con una mayor profundidad: las relacionadas con el derecho a la salud laboral y con los derechos digitales, así como el desarrollo de la institución mediante la negociación colectiva, mecanismo que podría equilibrar los distintos intereses y garantizar una mayor aceptación de estas regulaciones.

Single and Multiple Dose PK-PD Characterization for Carisoprodol. Part I: Pharmacokinetics, Metabolites, and 2C19 Phenotype Influence. Double-Blind, Placebo-Controlled Clinical Trial in Healthy Volunteers.

Carisoprodol was authorised in 1959 without a full pharmacokinetic-pharmacodynamic (PK-PD) characterisation. We designed a crossover, double-blind, placebo-controlled, randomized clinical trial to characterize the PKs of carisoprodol and its main active metabolite, meprobamate, after single (350 mg), multiple (350 mg/8 h, 14 days), and double (700 mg) doses of carisoprodol. Thirteen healthy volunteers were enrolled. After a single (350 mg) dose, the main carisoprodol parameters were (mean ± SD) Cmax: 2580 ± 1214 ng/mL, AUC0-∞: 8072 ± 6303 h·ng/mL, and half-life (T1/2): 2 ± 0.8 h. For meprobamate, the parameters were Cmax: 2181 ± 605 ng/mL and 34,529 ± 7747 h·ng/mL y 9 ± 1.9 h. Different profiles were found for extensive and poor 2C19 metabolizers. After 14 days of treatment (350 mg/8 h) the results for carisoprodol were (mean ± SD) Cmax: 2504 ± 730 ng/mL, AUC0-∞: 7451 ± 3615 h·ng/mL, and T1/2: 2 ± 0.7 h. For meprobamate (a steady state was reached), the parameters were Cmax: 5758 ± 1255 ng/mL and 79,699 ± 17,978 h·ng/mL y 8.7 ± 1.4 h. The study allowed for the full characterization of the pharmacokinetic profile of carisoprodol and meprobamate. Accumulation of meprobamate but not of carisoprodol was evident after 14 days of treatment.

COVID-19 Outbreak: Understanding Moral-Distress Experiences Faced by Healthcare Workers in British Columbia, Canada.

Pandemic-management plans shift the care model from patient-centred to public-centred and increase the risk of healthcare workers (HCWs) experiencing moral distress (MD). This study aimed to understand HCWs' MD experiences during the COVID-19 pandemic and to identify HCWs' preferred coping strategies. Based on a qualitative research methodology, three surveys were distributed at different stages of the pandemic response in British Columbia (BC), Canada. The thematic analysis of the data revealed common MD themes: concerns about ability to serve patients and about the risks intrinsic to the pandemic. Additionally, it revealed that COVID-19 fatigue and collateral impact of COVID-19 were important ethical challenges faced by the HCWs who completed the surveys. These experiences caused stress, anxiety, increased/decreased empathy, sleep disturbances, and feelings of helplessness. Respondents identified self-care and support provided by colleagues, family members, or friends as their main MD coping mechanisms. To a lesser extent, they also used formal sources of support provided by their employer and identified additional strategies they would like their employers to implement (e.g., improved access to mental health and wellness resources). These results may help inform pandemic policies for the future.

Electrophysiological correlates of the composite face illusion: disentangling perceptual and decisional components of holistic face processing in the human brain.

When the bottom halves of two faces differ, people's behavioral judgment of the identical top halves of those faces is impaired: they report that the top halves are different, and/or take more time than usual to provide a response. This behavioral measure is known as the composite face effect (CFE) and has traditionally been taken as evidence that faces are perceived holistically. Recently, however, it has been claimed that this effect is driven almost entirely by decisional, rather than perceptual, factors (Richler, Gauthier, Wenger, & Palmeri, 2008). To disentangle the contribution of perceptual and decisional brain processes, we aimed to obtain an event-related potential (ERP) measure of the CFE at a stage of face encoding (Jacques & Rossion, 2009) in the absence of a behavioral CFE effect. Sixteen participants performed a go/no-go task in an oddball paradigm, lifting a finger of their right or left hand when the top half of a face changed identity. This change of identity of the top of the face was associated with an increased ERP signal on occipito-temporal electrode sites at the N170 face-sensitive component (∼160 ms), the later decisional P3b component, and the lateralized readiness potential (LRP) starting at ∼350 ms. The N170 effect was observed equally early when only the unattended bottom part of the face changed, indicating that an identity change was perceived across the whole face in this condition. Importantly, there was no behavioral response bias for the bottom change trials, and no evidence of decisional biases from electrophysiological data (no P3b and LRP deflection in no-go trials). These data show that an early CFE can be measured in ERPs in the absence of any decisional response bias, indicating that the CFE reflects primarily the visual perception of the whole face.

Dexamethasone delivery to the ocular posterior segment by sustained-release Laponite formulation.

This paper presents a novel nanoformulation for sustained-release delivery of dexamethasone (DEX) to the ocular posterior segment using a Laponite (LAP) carrier-DEX/LAP 1:10 w w-1 formulation; 10 mg ml-1. In vivo ocular feasibility and pharmacokinetics after intravitreal (IV) and suprachoroidal (SC) administration in rabbit eyes are compared against IV administration of a DEX solution (1 mg ml-1). Thirty rabbit eyes were injected with the DEX/LAP formulation (15 suprachoroid/15 intravitreous). Ophthalmological signs were monitored at day 1 and at weeks 1-4-12-24 post-administration. Three eyes per sample time point were used to quantify DEX concentration using high-performance liquid chromatography-mass spectrometry. The ocular tissues' pharmacokinetic parameters (lens, vitreous humour, choroid-retina unit and sclera) were studied. DEX/LAP was well tolerated under both administration methods. Peak intraocular DEX levels from the DEX/LAP were detected in the vitreous humour after both deliveries soon after administration. The vitreous area under the curve was significantly greater after both DEX/LAP deliveries (IV: 205 968.47; SC: 11 442.22 ng g-1 d-1) than after IV administration of the DEX solution (317.17 ng g-1 d-1). Intravitreal DEX/LAP delivery extended higher vitreous DEX levels up to week 24 (466.32 ± 311.15 ng g-1). With SC delivery, DEX levels were detectable in the choroid-retina unit (12.04 ± 20.85 ng g-1) and sclera (25.46 ± 44.09 ng g-1) up to week 24. This study demonstrated the intraocular feasibility of both SC and IV administration of the DEX/LAP formulation. The LAP increased the intraocular retention time of DEX when compared with conventional solutions. DEX/LAP could be considered a biocompatible and useful sustained-release formulation for treating posterior-pole eye diseases.

Development of a system based on artificial intelligence to identify visual problems in children: study protocol of the TrackAI project.

INTRODUCTION: Around 70% to 80% of the 19 million visually disabled children in the world are due to a preventable or curable disease, if detected early enough. Vision screening in childhood is an evidence-based and cost-effective way to detect visual disorders. However, current screening programmes face several limitations: training required to perform them efficiently, lack of accurate screening tools and poor collaboration from young children.Some of these limitations can be overcome by new digital tools. Implementing a system based on artificial intelligence systems avoid the challenge of interpreting visual outcomes.The objective of the TrackAI Project is to develop a system to identify children with visual disorders. The system will have two main components: a novel visual test implemented in a digital device, DIVE (Device for an Integral Visual Examination); and artificial intelligence algorithms that will run on a smartphone to analyse automatically the visual data gathered by DIVE. METHODS AND ANALYSIS: This is a multicentre study, with at least five centres located in five geographically diverse study sites participating in the recruitment, covering Europe, USA and Asia.The study will include children aged between 6 months and 14 years, both with normal or abnormal visual development.The project will be divided in two consecutive phases: design and training of an artificial intelligence (AI) algorithm to identify visual problems, and system development and validation. The study protocol will consist of a comprehensive ophthalmological examination, performed by an experienced paediatric ophthalmologist, and an exam of the visual function using a DIVE.For the first part of the study, diagnostic labels will be given to each DIVE exam to train the neural network. For the validation, diagnosis provided by ophthalmologists will be compared with AI system outcomes. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of Good Clinical Practice. This protocol was approved by the Clinical Research Ethics Committee of Aragón, CEICA, on January 2019 (Code PI18/346).Results will be published in peer-reviewed journals and disseminated in scientific meetings. TRIAL REGISTRATION NUMBER: ISRCTN17316993.

Whole blood genome-wide transcriptome profiling and metagenomics next-generation sequencing in young infants with suspected sepsis in a low-and middle-income country: A study protocol.

Conducting collaborative and comprehensive epidemiological research on neonatal sepsis in low- and middle-income countries (LMICs) is challenging due to a lack of diagnostic tests. This prospective study protocol aims to obtain epidemiological data on bacterial sepsis in newborns and young infants at Kamuzu Central Hospital in Lilongwe, Malawi. The main goal is to determine if the use of whole blood transcriptome host immune response signatures can help in the identification of infants who have sepsis of bacterial causes. The protocol includes a detailed clinical assessment with vital sign measurements, strict aseptic blood culture protocol with state-of-the-art microbial analyses and RNA-sequencing and metagenomics evaluations of host responses and pathogens, respectively. We also discuss the directions of a brief analysis plan for RNA sequencing data. This study will provide robust epidemiological data for sepsis in neonates and young infants in a setting where sepsis confers an inordinate burden of disease.

Use of Machine Learning for Predicting Escitalopram Treatment Outcome From Electroencephalography Recordings in Adult Patients With Depression.

Importance: Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an individual patient's response to treatment could significantly reduce the burden of depression. Objective: To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression. Design, Setting, and Participants: This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment. Interventions: All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment. Main Outcomes and Measures: The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%. Results: Of the 122 participants who completed a baseline EEG recording (mean [SD] age, 36.3 [12.7] years; 76 [62.3%] female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%). Conclusions and Relevance: These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.