ABSTRACT
Human immune responses to viral infections are highly variable, but the genetic factors that contribute to this variability are not well characterized. We used VirScan, a high-throughput epitope scanning technology, to analyze pan-viral antibody reactivity profiles of twins and SNP-genotyped individuals. Using these data, we determined the heritability and genomic loci associated with antibody epitope selection, response breadth, and control of Epstein-Barr virus (EBV) viral load. 107 EBV peptide reactivities were heritable and at least two Epstein-Barr nuclear antigen 2 (EBNA-2) reactivities were associated with variants in the MHC class II locus. We identified an EBV serosignature that predicted viral load in peripheral blood mononuclear cells and was associated with variants in the MHC class I locus. Our study illustrates the utility of epitope profiling to investigate the genetics of pathogen immunity, reports heritable features of the antibody response to viruses, and identifies specific HLA loci important for EBV epitope selection.
Subject(s)
Antibodies, Viral/metabolism , Epitopes/metabolism , Epstein-Barr Virus Infections/genetics , Epstein-Barr Virus Nuclear Antigens/metabolism , Genotype , Herpesvirus 4, Human/physiology , Immunodominant Epitopes/metabolism , Viral Proteins/metabolism , Adolescent , Adult , Aged , Cohort Studies , Epitope Mapping , Epitopes/genetics , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Nuclear Antigens/genetics , Female , HLA Antigens/genetics , HLA Antigens/metabolism , Humans , Immunity, Humoral , Immunodominant Epitopes/genetics , Male , Middle Aged , Peptides/genetics , Polymorphism, Single Nucleotide , Quantitative Trait, Heritable , Seroepidemiologic Studies , Viral Load , Viral Proteins/genetics , Young AdultABSTRACT
Microbial exposures are crucial environmental factors that impact healthspan by sculpting the immune system and microbiota. Antibody profiling via Phage ImmunoPrecipitation Sequencing (PhIP-Seq) provides a high-throughput, cost-effective approach for detecting exposure and response to microbial protein products. We designed and constructed a library of 95,601 56-amino acid peptide tiles spanning 14,430 proteins with "toxin" or "virulence factor" keyword annotations. We used PhIP-Seq to profile the antibodies of â¼1,000 individuals against this "ToxScan" library. In addition to enumerating immunodominant antibody epitopes, we studied the age-dependent stability of the ToxScan profile and used a genome-wide association study to find that the MHC-II locus modulates bacterial epitope selection. We detected previously described anti-flagellin antibody responses in a Crohn's disease cohort and identified an association between anti-flagellin antibodies and juvenile dermatomyositis. PhIP-Seq with the ToxScan library is thus an effective tool for studying the environmental determinants of health and disease at cohort scale.
Subject(s)
Bacteriophages , Peptide Library , Amino Acid Sequence , Antibodies , Antibody Formation , Bacteriophages/genetics , Genome-Wide Association Study , Humans , Immunodominant Epitopes , Prevalence , Virulence Factors/geneticsABSTRACT
Non-coding genetic variants may cause disease by modulating gene expression. However, identifying these expression quantitative trait loci (eQTLs) is complicated by differences in gene regulation across fluid functional cell states within cell types. These states-for example, neurotransmitter-driven programs in astrocytes or perivascular fibroblast differentiation-are obscured in eQTL studies that aggregate cells1,2. Here we modelled eQTLs at single-cell resolution in one complex cell type: memory T cells. Using more than 500,000 unstimulated memory T cells from 259 Peruvian individuals, we show that around one-third of 6,511 cis-eQTLs had effects that were mediated by continuous multimodally defined cell states, such as cytotoxicity and regulatory capacity. In some loci, independent eQTL variants had opposing cell-state relationships. Autoimmune variants were enriched in cell-state-dependent eQTLs, including risk variants for rheumatoid arthritis near ORMDL3 and CTLA4; this indicates that cell-state context is crucial to understanding potential eQTL pathogenicity. Moreover, continuous cell states explained more variation in eQTLs than did conventional discrete categories, such as CD4+ versus CD8+, suggesting that modelling eQTLs and cell states at single-cell resolution can expand insight into gene regulation in functionally heterogeneous cell types.
Subject(s)
Genetic Predisposition to Disease , Memory T Cells , Quantitative Trait Loci , Gene Expression Regulation , Genetic Predisposition to Disease/genetics , Humans , Memory T Cells/immunology , Memory T Cells/metabolism , Peru , Quantitative Trait Loci/geneticsABSTRACT
OBJECTIVE: To describe the texture characteristics in several anatomical structures within fetal ultrasound images by applying an image segmentation technique through an application developed in MATLAB mathematical processing software. METHODS: Prospective descriptive observational study with an analytical component. 2D fetal ultrasound images were acquired in patients admitted to the Maternal Fetal Medicine Unit of the Hospital de San José, Bogotá-Colombia. These images were loaded into the developed application to carry out the segmentation and characterization stages by means of 23 numerical texture descriptors. The data were analyzed with central tendency measures and through an embedding process and Euclidean distance. RESULTS: Forty ultrasound images were included, characterizing 54 structures of the fetal placenta, skull, thorax, and abdomen. By embedding the descriptors, the differentiation of biologically known structures as distinct was achieved, as well as the non-differentiation of similar structures, evidenced using 2D and 3D graphs and numerical data with statistical significance. CONCLUSION: The texture characterization of the labeled structures in fetal ultrasound images through the numerical descriptors allows the accurate discrimination of these structures.
Subject(s)
Fetus , Ultrasonography, Prenatal , Pregnancy , Female , Humans , Ultrasonography, Prenatal/methods , Ultrasonography , Fetus/diagnostic imaging , Placenta , Prospective Studies , Image Processing, Computer-Assisted/methodsABSTRACT
Refractive errors, myopia, and hyperopia are common visual disorders greatly affecting older individuals. Refraction is determined by genetic factors but only a small percentage of its variation has been explained. We performed a genetic association analysis with three ocular phenotypes: spherical equivalent (a continous measure of refraction), axial length, and corneal curvature in 1,871 European-Americans from the Beaver Dam Eye Study. Individuals were genotyped on the Illumina exome array and imputed to the Haplotype Reference Consortium reference panel. After increasing the number of analyzed variants in targeted protein-coding regions 10-fold via imputation, we confirmed associations for two previously known loci with corneal curvature (chr4q12, rs2114039; g.55092626T > C, ß = -0.03 (95% confidence interval [CI]): -0.06, -0.01, P value = 0.01) and spherical equivalent (chr15q14, rs634990; g.35006073T > C, ß = -0.27, 95% CI: -0.45, -0.09, P value = 3.79 × 10-3 ). Despite increased single nucleotide polymorphism (SNP) density, we did not detect any novel significant variants after correction for multiple comparisons. In summary, we confirmed two previous loci associated with corneal curvature and spherical equivalent in a European-American population highlighting the potential biological role of those regions in these traits.
Subject(s)
Chromosomes, Human, Pair 15/genetics , Chromosomes, Human, Pair 4/genetics , Exome Sequencing/methods , Polymorphism, Single Nucleotide , Refractive Errors/genetics , White People/genetics , Aged , Aged, 80 and over , Chromosome Mapping , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Phenotype , United States/ethnologyABSTRACT
Background: Cryptosporidium species are enteric protozoa that cause significant morbidity and mortality in children worldwide. We characterized the epidemiology of Cryptosporidium in children from 8 resource-limited sites in Africa, Asia, and South America. Methods: Children were enrolled within 17 days of birth and followed twice weekly for 24 months. Diarrheal and monthly surveillance stool samples were tested for Cryptosporidium by enzyme-linked immunosorbent assay. Socioeconomic data were collected by survey, and anthropometry was measured monthly. Results: Sixty-five percent (962/1486) of children had a Cryptosporidium infection and 54% (802/1486) had at least 1 Cryptosporidium-associated diarrheal episode. Cryptosporidium diarrhea was more likely to be associated with dehydration (16.5% vs 8.3%, P < .01). Rates of Cryptosporidium diarrhea were highest in the Peru (10.9%) and Pakistan (9.2%) sites. In multivariable regression analysis, overcrowding at home was a significant risk factor for infection in the Bangladesh site (odds ratio, 2.3 [95% confidence interval {CI}, 1.2-4.6]). Multiple linear regression demonstrated a decreased length-for-age z score at 24 months in Cryptosporidium-positive children in the India (ß = -.26 [95% CI, -.51 to -.01]) and Bangladesh (ß = -.20 [95% CI, -.44 to .05]) sites. Conclusions: This multicountry cohort study confirmed the association of Cryptosporidium infection with stunting in 2 South Asian sites, highlighting the significance of cryptosporidiosis as a risk factor for poor growth. We observed that the rate, age of onset, and number of repeat infections varied per site; future interventions should be targeted per region to maximize success.
Subject(s)
Cryptosporidiosis/epidemiology , Diarrhea/epidemiology , Poverty Areas , Africa/epidemiology , Asia/epidemiology , Child, Preschool , Cohort Studies , Crowding , Cryptosporidium/isolation & purification , Diarrhea/parasitology , Feces/parasitology , Female , Growth Disorders/parasitology , Humans , Infant , Infant, Newborn , Male , Malnutrition/parasitology , Regression Analysis , Risk Factors , Socioeconomic Factors , South America/epidemiology , Surveys and QuestionnairesABSTRACT
Background: Traumatic ventricular septal defects (VSDs) are life-threatening complications of blunt or stab chest trauma. The standard of care is surgical closure or secondary percutaneous closure due to high surgical risk because of recent sternotomy. Case summary: We present a 22-year-old male with an ice pick-related VSD. It was successfully closed by primary percutaneous approach. After 6 months, the echo Doppler shows no residual shunt, normal pulmonary artery pressure, and normal biventricular function. Discussion: To our knowledge, this is one of the first primary percutaneous closures for knife-related VSD. Early diagnosis and treatment can prevent heart failure and long-term complications. Less necrotic tissue surrounding the VSD compared with post-infarction (PI) VSD allows for early and secure treatment. Percutaneous closure is a feasible and effective choice even in patients who had no prior sternotomy or who reject surgery as a primary treatment strategy.
ABSTRACT
OBJECTIVE: We aim to report the outcomes and feasibility of endoscopic spine surgery used to treat symptomatic spinal metastases patients. This is the most extensive series of spinal metastases patients who underwent endoscopic spine surgery. METHODS: A worldwide collaborative network group of endoscopic spine surgeons, named 'ESSSORG,' was established. Patients diagnosed with spinal metastases who underwent endoscopic spine surgery from 2012 to 2022 were retrospectively reviewed. All related patient data and clinical outcomes were gathered and analyzed before the surgery and the followtime period of 2 weeks, 1 month, 3 months, and 6 months. RESULTS: A total of 29 patients from South Korea, Thailand, Taiwan, Mexico, Brazil, Argentina, Chile, and India, were included. The mean age was 59.59 years, and 11 of them were female. The total number of decompressed levels was 40. The technique was relatively equal (15 uniportal; 14 biportal). The average length of admission was 4.41 days. Of all patients with an American Spinal Injury Association Impairment Scale of D or lower before surgery, 62.06% reported having at least one recovery grade after the surgery. Almost all clinical outcomes parameters statistically significantly improved and maintained from 2 weeks to 6 months after the surgery. Few surgical-related complications (4 cases) were reported. CONCLUSION: Endoscopic spine surgery is a valid option for treating spinal metastases patients as it could yield comparable results to other minimally invasive spine surgery techniques. As the aim is to improve the quality of life, this procedure is valuable and holds value in palliative oncologic spine surgery.
ABSTRACT
The human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation and cancer. While coding variation in HLA genes has been extensively documented, regulatory genetic variation modulating HLA expression levels has not been comprehensively investigated. Here we mapped expression quantitative trait loci (eQTLs) for classical HLA genes across 1,073 individuals and 1,131,414 single cells from three tissues. To mitigate technical confounding, we developed scHLApers, a pipeline to accurately quantify single-cell HLA expression using personalized reference genomes. We identified cell-type-specific cis-eQTLs for every classical HLA gene. Modeling eQTLs at single-cell resolution revealed that many eQTL effects are dynamic across cell states even within a cell type. HLA-DQ genes exhibit particularly cell-state-dependent effects within myeloid, B and T cells. For example, a T cell HLA-DQA1 eQTL ( rs3104371 ) is strongest in cytotoxic cells. Dynamic HLA regulation may underlie important interindividual variability in immune responses.
Subject(s)
Gene Expression Regulation , Quantitative Trait Loci , Humans , Gene Expression Regulation/genetics , Quantitative Trait Loci/genetics , Genome-Wide Association Study , Polymorphism, Single NucleotideABSTRACT
The human leukocyte antigen (HLA) locus plays a critical role in complex traits spanning autoimmune and infectious diseases, transplantation, and cancer. While coding variation in HLA genes has been extensively documented, regulatory genetic variation modulating HLA expression levels has not been comprehensively investigated. Here, we mapped expression quantitative trait loci (eQTLs) for classical HLA genes across 1,073 individuals and 1,131,414 single cells from three tissues, using personalized reference genomes to mitigate technical confounding. We identified cell-type-specific cis-eQTLs for every classical HLA gene. Modeling eQTLs at single-cell resolution revealed that many eQTL effects are dynamic across cell states even within a cell type. HLA-DQ genes exhibit particularly cell-state-dependent effects within myeloid, B, and T cells. Dynamic HLA regulation may underlie important interindividual variability in immune responses.
ABSTRACT
We present an algorithm based on three PCR assays for Leishmania (Viannia) species identification and assessed its performance using 70 specimens from Peruvian patients. The succession of the assayed targets can be ordered according to species prevalence. Sequential progression through the algorithm reduced the number of samples here studied by approximately 30% after each step.
Subject(s)
Leishmania/isolation & purification , Leishmaniasis, Cutaneous/diagnosis , Molecular Diagnostic Techniques/methods , Parasitology/methods , Polymerase Chain Reaction/methods , Algorithms , Humans , PeruABSTRACT
Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present a hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor and 13 subclonal lines across 9 time points over 5 broad conditions: self-renewal, early neuronal differentiation, neural precursor cells (NPCs), assembled rosettes, and differentiated neuronal cells. We identify widespread changes in the expression of both individual features and global patterns of transcription. We next demonstrate that co-culturing human NPCs with rodent astrocytes results in mutually synergistic maturation, and that cell type-specific expression data can be extracted using only sequencing read alignments without cell sorting. We lastly adapt a previously generated RNA deconvolution approach to single-cell expression data to estimate the relative neuronal maturity of iPSC-derived neuronal cultures and human brain tissue. Using many public datasets, we demonstrate neuronal cultures are maturationally heterogeneous but contain subsets of neurons more mature than previously observed.
Subject(s)
Cell Differentiation/genetics , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/physiology , Neural Stem Cells/physiology , Transcriptome , Algorithms , Animals , Astrocytes/cytology , Cells, Cultured , Cerebral Cortex/cytology , Coculture Techniques , Databases, Genetic , Gene Expression Regulation , Humans , Models, Neurological , Neural Stem Cells/cytology , Neurons/cytology , Neurons/physiology , RatsABSTRACT
Molecular methods such as PCR have become attractive tools for diagnosis of cutaneous leishmaniasis (CL), both for their high sensitivity and for their specificity. However, their practical use in routine diagnosis is limited due to the infrastructural requirements and the lack of any standardization. Recently, a simplified and standardized PCR format for molecular detection of Leishmania was developed. The Leishmania OligoC-TesT is based on simple and rapid detection using a dipstick with PCR-amplified Leishmania DNA. In this study, we estimated the diagnostic accuracy of the Leishmania OligoC-TesT for 61 specimens from 44 CL-suspected patients presenting at the leishmaniasis clinic of the Instituto de Medicina Tropical Alexander von Humboldt, Peru. On the basis of parasitological detection and the leishmanin skin test (LST), patients were classified as (i) confirmed CL cases, (ii) LST-positive cases, and (iii) LST-negative cases. The sensitivities of the Leishmania OligoC-TesT was 74% (95% confidence interval (CI), 60.5% to 84.1%) for lesion aspirates and 92% (95% CI, 81.2% to 96.9%) for scrapings. A significantly higher sensitivity was observed with a conventional PCR targeting the kinetoplast DNA on the aspirates (94%) (P = 0.001), while there was no significant difference in sensitivity for the lesion scrapings (88%) (P = 0.317). In addition, the Leishmania OligoC-TesT was evaluated for 13 CL-suspected patients in two different peripheral health centers in the central jungle of Peru. Our findings clearly indicate the high accuracy of the Leishmania OligoC-TesT for lesion scrapings for simple and rapid molecular diagnosis of CL in Peru.
Subject(s)
Leishmania/isolation & purification , Leishmaniasis, Cutaneous/diagnosis , Molecular Diagnostic Techniques/methods , Polymerase Chain Reaction/methods , Reagent Kits, Diagnostic , Animals , Humans , Leishmania/genetics , Leishmaniasis, Cutaneous/parasitology , Peru , Sensitivity and Specificity , Skin/parasitologyABSTRACT
The hippocampus formation, although prominently implicated in schizophrenia pathogenesis, has been overlooked in large-scale genomics efforts in the schizophrenic brain. We performed RNA-seq in hippocampi and dorsolateral prefrontal cortices (DLPFCs) from 551 individuals (286 with schizophrenia). We identified substantial regional differences in gene expression and found widespread developmental differences that were independent of cellular composition. We identified 48 and 245 differentially expressed genes (DEGs) associated with schizophrenia within the hippocampus and DLPFC, with little overlap between the brain regions. 124 of 163 (76.6%) of schizophrenia GWAS risk loci contained eQTLs in any region. Transcriptome-wide association studies in each region identified many novel schizophrenia risk features that were brain region-specific. Last, we identified potential molecular correlates of in vivo evidence of altered prefrontal-hippocampal functional coherence in schizophrenia. These results underscore the complexity and regional heterogeneity of the transcriptional correlates of schizophrenia and offer new insights into potentially causative biology.
Subject(s)
Frontal Lobe , Gene Expression Regulation, Developmental/physiology , Hippocampus , Schizophrenia/genetics , Schizophrenia/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Frontal Lobe/embryology , Frontal Lobe/growth & development , Frontal Lobe/metabolism , Gene Ontology , Genetic Predisposition to Disease , Genome-Wide Association Study , Hippocampus/embryology , Hippocampus/growth & development , Hippocampus/metabolism , Humans , Male , Middle Aged , Young AdultABSTRACT
Resumen La polimiositis es una miopatía autoinmune que causa cada año a nivel mundial 4 casos por cada millón de habitantes, es de diagnóstico clínico y necesita tratamiento rápido y agresivo porque puede llevar a desenlaces fatales. Esta patología es infrecuente en hombres con una proporción mujer/hombre de 2.5:1, por lo que el objetivo del artículo fue describir y comparar con la literatura el caso de un paciente masculino con polimiositis quien debutó con debilidad muscular y dolor poliarticular de 20 días de evolución, con valores de creatina quinasa de 24000 UI/L, asociado a pérdida de peso y respondiendo adecuadamente al tratamiento médico brindado en el momento. Después de 3 años asintomático, sufrió una agudización que fue manejada con medicamentos de primera línea, pero sin mejoría, por lo que requirió metilprednisolona oral a altas dosis e inmunomoduladores. En ningún momento presentó compromiso de órganos vitales, actualmente es sintomático y se encuentra en manejo médico. MÉD.UIS.2022;35(1):49-56.
Abstract Polymyositis is an autoimmune myopathy and each year it causes 4 cases per million in the worldwide population, it is clinically diagnosed and needs rapid and aggressive treatment because it can lead to fatal outcomes. This pathology is infrequent in men, with a proportion women/men 2.5:1, the objective of the article was to describe and compare with the literature the case of a male patient with polymyositis, who presented with muscle weakness and polyarticular pain of 20 days of evolution, with Creatine kinase values of 24,000 IU/L, associated with weight loss, and responding adequately to the medical treatment provided at the time. After 3 years asymptomatic, he suffered an acute phase that was managed with first-line medications but without improvement, for which he required oral methylprednisolone at high doses and inmunomodulators. At no time did he present vital organ involvement, he is currently symptomatic and is under medical management. MÉD.UIS.2022;35(1):49-56.
Subject(s)
Humans , Middle Aged , Polymyositis , Rheumatology , Autoimmune Diseases , Muscle Weakness , Creatine KinaseABSTRACT
Reconstruction of brain sources from magnetoencephalography and electroencephalography (M/EEG) data is a well known problem in the neuroengineering field. A inverse problem should be solved and several methods have been proposed. Low Resolution Electromagnetic Tomography (LORETA) and the different variations proposed as standardized LORETA (sLORETA) and the standardized weighted LORETA (swLORETA) have solved the inverse problem following a non-parametric approach, that is by setting dipoles in the whole brain domain in order to estimate the dipole positions from the M/EEG data and assuming some spatial priors. Errors in the reconstruction of sources are presented due the low spatial resolution of the LORETA framework and the influence of noise in the observable data. In this work a kernel temporal enhancement (kTE) is proposed in order to build a preprocessing stage of the data that allows in combination with the swLORETA method a improvement in the source reconstruction. The results are quantified in terms of three dipole error localization metrics and the strategy of swLORETA + kTE obtained the best results across different signal to noise ratio (SNR) in random dipoles simulation from synthetic EEG data.
Subject(s)
Algorithms , Brain Mapping/methods , Brain/diagnostic imaging , Electromagnetic Phenomena , Tomography/methods , Electroencephalography , Humans , Signal-To-Noise RatioABSTRACT
RESUMEN Introducción: El paludismo es una parasitosis producida por protozoos del género Plasmodium que puede causar disfunción orgánica. A pesar del control y prevención, es un problema de salud pública que contribuye a la morbilidad y mortalidad, especialmente en países tropicales. Objetivo: Identificar factores predisponentes para la complicación del paludismo en el departamento del Cauca, Colombia. Métodos: Se desarrolló un estudio observacional tipo casos y controles no pareados en el departamento del Cauca durante 2016-2019 con pacientes notificados al Sistema Nacional de Vigilancia en Salud Pública. Se recolectaron 445 pacientes con paludismo, aquellos con alguna complicación fueron definidos como casos (n= 89) y a cada uno se asignaron 4 controles (n= 356). La información de los complicados se contrastó con la historia clínica. Resultados: De la población estudiada (n= 445), 281 fueron hombres (63,1%), la edad media fue 28,34 años y 397 eran originarios del departamento del Cauca (89,2%). Noveta y nueve requirieron hospitalización (22,2 %) y tres fallecieron (0,7 %). Sesenta y uno complicados fueron por P. falciparum (68,5%). Los casos importados (p= 0,000), etnia negra (p=0,000), tratamiento después de 3 días (p= 0,000), procedencia urbana (p= 0,025), régimen contributivo (p=0,026), P. vivax (p= 0,000) y presencia de gametocitos (p=0,000) se asociaron con complicaciones. Conclusiones: La ubicación geográfica, redes hospitalarias ineficientes, desconocimiento de la enfermedad, entre otros factores deben intervenirse. La falta de estudios sobre paludismo y sus complicaciones limitan tomar decisiones.
ABSTRACT Introduction: Malaria is a parasitic infection caused by protozoa of the genus Plasmodium. This condition may lead to organ dysfunction. Despite the actions implemented to control and prevent malaria, it continues to be a public health problem contributing to morbidity and mortality, mainly in tropical countries. Objective: Identify the predisposing factors for complicated malaria in Cauca Department, Colombia. Methods: An observational non-paired case-control study was conducted in Cauca Department in the period 2016-2019. The study sample was 445 patients notified to the National Public Health Surveillance System. Patients with complications were defined as cases (n= 89). Each case was assigned four controls (n= 356). Information about complicated cases was contrasted with the medical records. Results: Of the total population studied (n= 445), 281 were men (63.1%) and 397 were from Cauca Department (89.2%). Mean age was 28.34 years. Ninety-nine patients required hospitalization (22.2%) and three died (0.7%). Sixty-one of the complicated patients were infected by P. falciparum (68.5%). The following factors were associated to complications: imported cases (p= 0.000), black ethnic group (p=0.000), treatment after three days (p= 0.000), urban area of residence (p= 0.025), contributory regime (p=0.026), P. vivax (p= 0.000) and presence of gametocytes (p=0.000). Conclusions: Actions should be implemented concerning geographic location, inefficient hospital networks and insufficient knowledge about the disease, among other factors. Lack of studies about malaria and its complications limit decision making.
ABSTRACT
BACKGROUND: Cryptosporidiosis is a common cause of infectious diarrhea in young children worldwide, and is a significant contributor to under-five mortality. Current treatment options are limited in young children. In this study, we describe the natural history of Cryptosporidium spp. infection in a birth cohort of children in Bangladesh and evaluate for association with malnutrition. METHODOLOGY/PRINCIPAL FINDINGS: This is a longitudinal birth cohort study of 392 slum-dwelling Bangladeshi children followed over the first two years of life from 2008 to 2014. Children were monitored for diarrheal disease, and stool was tested for intestinal protozoa. Anthropometric measurements were taken at 3-month intervals. A subset of Cryptosporidium positive stools were genotyped for species and revealed that C. hominis was isolated from over 90% of samples. In the first two years of life, 77% of children experienced at least one infection with Cryptosporidium spp. Non-diarrheal infection (67%) was more common than diarrheal infection (6.3%) although 27% of children had both types of infection. Extreme poverty was associated with higher rates of infection (chi-square, 49.7% vs 33.3%, p = 0.006). Malnutrition was common in this cohort, 56% of children had stunted growth by age two. Children with Cryptosporidium spp. infection had a greater than 2-fold increased risk of severe stunting at age two compared to uninfected children (odds ratio 2.69, 95% CI 1.17, 6.15, p = 0.019) independent of sex, income, maternal body-mass index, maternal education and weight for age adjusted z (WAZ) score at birth. CONCLUSIONS/SIGNIFICANCE: Cryptosporidium infection is common (77%) in this cohort of slum-dwelling Bangladeshi children, and both non-diarrheal and diarrheal infections are significantly associated with a child's growth at 2 years of age.
Subject(s)
Cryptosporidiosis/complications , Cryptosporidiosis/epidemiology , Infant Nutrition Disorders/complications , Malnutrition/complications , Malnutrition/epidemiology , Poverty Areas , Bangladesh/epidemiology , Cohort Studies , Cryptosporidiosis/parasitology , Cryptosporidium/classification , Cryptosporidium/genetics , Cryptosporidium/isolation & purification , Diarrhea/parasitology , Female , Genotype , Humans , Infant , Infant Nutrition Disorders/epidemiology , Longitudinal Studies , Male , Prospective Studies , Risk FactorsABSTRACT
Human emotion recognition (HER) allows the assessment of an affective state of a subject. Until recently, such emotional states were described in terms of discrete emotions, like happiness or contempt. In order to cover a high range of emotions, researchers in the field have introduced different dimensional spaces for emotion description that allow the characterization of affective states in terms of several variables or dimensions that measure distinct aspects of the emotion. One of the most common of such dimensional spaces is the bidimensional Arousal/Valence space. To the best of our knowledge, all HER systems so far have modelled independently, the dimensions in these dimensional spaces. In this paper, we study the effect of modelling the output dimensions simultaneously and show experimentally the advantages in modeling them in this way. We consider a multimodal approach by including features from the Electroencephalogram and a few physiological signals. For modelling the multiple outputs, we employ a multiple output regressor based on support vector machines. We also include an stage of feature selection that is developed within an embedded approach known as Recursive Feature Elimination (RFE), proposed initially for SVM. The results show that several features can be eliminated using the multiple output support vector regressor with RFE without affecting the performance of the regressor. From the analysis of the features selected in smaller subsets via RFE, it can be observed that the signals that are more informative into the arousal and valence space discrimination are the EEG, Electrooculogram/Electromiogram (EOG/EMG) and the Galvanic Skin Response (GSR).