Structure analysis and lesion detection from retinal fundus images

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Ocular pathology is one of the main health problems worldwide. The number of people with retinopathy symptoms has increased considerably in recent years. Early adequate treatment has demonstrated to be effective to avoid the loss of the vision. The analysis of fundus images is a non intrusive option for periodical retinal screening. Different models designed for the analysis of retinal images are based on supervised methods, which require of hand labelled images and processing time as part of the training stage. On the other hand most of the methods have been designed under the basis of specific characteristics of the retinal images (e.g. field of view, resolution). This compromises its performance to a reduce group of retinal image with similar features. For these reasons an unsupervised model for the analysis of retinal image is required, a model that can work without human supervision or interaction. And that is able to perform on retinal images with different characteristics. In this research, we have worked on the development of this type of model. The system locates the eye structures (e.g. optic disc and blood vessels) as first step. Later, these structures are masked out from the retinal image in order to create a clear field to perform the lesion detection. We have selected the Graph Cut technique as a base to design the retinal structures segmentation methods. This selection allows incorporating prior knowledge to constraint the searching for the optimal segmentation. Different link weight assignments were formulated in order to attend the specific needs of the retinal structures (e.g. shape). This research project has put to work together the fields of image processing and ophthalmology to create a novel system that contribute significantly to the state of the art in medical image analysis. This new knowledge provides a new alternative to address the analysis of medical images and opens a new panorama for researchers exploring this research area.Mexican National Council of Science and Technolog

Enlaces in Reflections and (Re)memberings as Latina Border-Crossers: Journeys of Childhood and Professional Un/Welcomings

We are humbled to be part of this special issue honoring the life work of Jonathan Silin. His scholarship and activism have opened spaces for future generations, like our own, to share our testimonios. We are straddling between being former early childhood teachers and current teacher educators—between our profe lives and our everyday lived experiences as Latina border crossers. Testimonios, which we engage in for this piece, have herstorically captured intimate tellings that connect individual struggles and strengths to the larger collective (Delgado Bernal, Burciaga, & Flores Carmona, 2012; Latina Feminist Group, 2001). It is in these testimonios that women of color (and in our case, Latina) scholars have felt hospitality and welcoming. Although our tellings may be painful to write and read, Lorde (1984) and Anzaldúa (1987) remind us that we must write for survival and tell our stories in our own words. In that way, we acknowledge the deep intergenerational wounds felt by Latinx peoples and Black, Indigenous, and People of Color (BIPOC), while providing a means for conocimiento/healing

La calidad de vida en adultos con diabetes mellitus tipo 2 en centros de salud de Guadalajara, Jalisco (México)

Objetivo: Evaluar la percepción de Calidad de Vida Relacionada con la Salud (CVRS) de Objetivos: Evaluar la relación de la diabetes sobre la calidad de vida, utilizando el cuestionario Diabetes 39 en pacientes diagnosticados como diabéticos que acuden a visita ambulatoria a centros de salud. Materiales y métodos: Con un diseño transversal en una muestra no probabilística determinada por un periodo de tiempo en cuatro centros de salud de la Secretaría de Salud Jalisco (SSJ) en la Zona Metropolitana de Guadalajara, en pacientes que acuden a control de diabetes. Se estudiaron tres variables: calidad de vida, socio-demográficas y específicas de la enfermedad. Resultados: En la muestra de 198 pacientes ambulatorios con diabetes tipo 2 y con un tiempo de evolución de 9.51 ± 8 años, un 76.7% sin complicaciones relacionadas con la diabetes, una mitad (47.9%) fueron tratados con dieta. Con base en los dominios medidos con el Diabetes 39, las puntuaciones más altas se dan en la "calidad de vida" con un dete- rioro en la misma seguida de la percepción que se tiene sobre la "severidad de la diabetes", de los cinco dominios los de "energía y movilidad" y el de "funcionamiento sexual" fueron los que tienen una mayor media del total de la muestra. Las diferencias significativas por género se dan en el dominio de "funcionamiento sexual" para los hombres. Conclusiones: La calidad de vida se ve afectada en pacientes con diabetes, especialmen- te en el dominio de energía y movilidad y en el funcionamiento sexual, lo que indica la necesidad de un programa de intervención en actividades física-recreativas y en asesoría educativa-psicológica. Palabras clave: Diabetes 39, Calidad de vida, Diabetes mellitus, Adultos. Abstract Objectives: To evaluate the relationships of the diabetes on the quality of life, being used questionnaire Diabetes 39 to patients diagnosed like diabetics who go ambulatory visit to health centers. Materials and methods: With a transversal design in a nonrandom sampling determi- ned by a time period in four centers of health of the salubrity secretary was made (SSA) in the Metropolitan Zone of Guadalajara, in patients attending diabetic control. Three variables were studied: quality of life, socio-demographics and the disease specific. Results: In the sample of 198 ambulatory patients with diabetes type 2 iand with a du- ration of 9.51 ± 8 years, 76,7% without diabetes-related complications, one half (47.95) were treated with diet. Based on the dominions measured with Diabetes 39, the highest scores occur in the dominion of "quality of life" with a followed deterioration in their lives and in their perception about the "severity of the diabetes", of the five dominions those of "energy and mobility" and the one of "sexual operation" was those that they have a greater average of the total of the sample. The significant differences by gender differences exist in the domain of "sexual performance" for men. Conclusions: The quality of life is affected in patients with diabetes, especially in the do- minion of energy and mobility and in the sexual operation, which indicates the necessity of a program of intervention in physical-recreational activities and educative-psychological consultant's office. The greater negative impact of the diabetes in the quality of life was associated with man, low entrance to the average and with presence of complications by the diabetes. Keywords: Diabetes 39, Quality of life, Diabetes mellitus, Adults

Myocardial Response to Biomechanical Stress

Biomechanical stress of the myocardium is the situation resulting from hypoxia, hypertension, and other forms of myocardial injury, that invariably lead to increased demands for cardiac work and/or loss of functional myocardium. As a consequence of biomechanical stress a number of responses develop involving all the myocardial cells, namely cardiomyocytes. As a result some myocardial phenotypic changes develop that are initially compensatory (i.e., hypertrophy) but which may mediate the eventual decline in myocardial function that occurs with the transition from hypertrophy to failure in conditions of persistent stress (i.e., apoptosis and fibrosis). This review focuses on the steps involved in the response of the myocardium to biomechanical stress and highlights the most recent developments in the molecular mechanisms involved in the development of heart failure

Novel Somatic Genetic Variants as Predictors of Resistance to EGFR-Targeted Therapies in Metastatic Colorectal Cancer Patients

Background: About 40% of RAS/BRAF wild-type metastatic colorectal cancer (mCRC) patients undergoing anti-EGFR-based therapy have poor outcomes. Treatment failure is not only associated with poorer prognosis but higher healthcare costs. Our aim was to identify novel somatic genetic variants in the primary tumor and assess their effect on anti-EGFR response. Patients and Methods: Tumor (somatic) and blood (germline) DNA samples were obtained from two well-defined cohorts of mCRC patients, those sensitive and those resistant to EGFR blockade. Genetic variant screening of 43 EGFR-related genes was performed using targeted next-generation sequencing (NGS). Relevant clinical data were collected through chart review to assess genetic results. Results: Among 61 patients, 38 were sensitive and 23 were resistant to treatment. We identified eight somatic variants that predicted non-response. Three were located in insulin-related genes (I668N and E1218K in IGF1R, T1156M in IRS2) and three in genes belonging to the LRIG family (T152T in LRIG1, S697L in LRIG2 and V812M in LRIG3). The remaining two variants were found in NRAS (G115Efs*46) and PDGFRA (T301T). We did not identify any somatic variants related to good response. Conclusions: This study provides evidence that novel somatic genetic variants along the EGFR-triggered pathway could modulate the response to anti-EGFR drugs in mCRC patients. It also highlights the influence of insulin-related genes and LRIG genes on anti-EGFR efficacy. Our findings could help characterize patients who are resistant to anti-EGFR blockade despite harboring RAS/BRAF wild-type tumors

The activity of circulating dipeptidyl peptidase-4 is associated with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus

Background: Patients with type 2 diabetes mellitus (T2DM) present subclinical left ventricular systolic and/or diastolic dysfunction (LVD). Dipeptidyl peptidase-4 (DPP4) inactivates peptides that possess cardioprotective actions. Our aim was to analyze whether the activity of circulating DPP4 is associated with echocardiographically defined LVD in asymptomatic patients with T2DM. Methods: In this cross-sectional study, we examined 83 T2DM patients with no coronary or valve heart disease and 59 age and gender-matched non-diabetic subjects. Plasma DPP4 activity (DPP4a) was measured by enzymatic assay and serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by enzyme-linked immunosorbent assay. LV function was assessed by two-dimensional echocardiographic imaging, targeted M-mode recordings and Doppler ultrasound measurements. Differences in means were assessed by t-tests and one-way ANOVA. Associations were assessed by adjusted multiple linear regression and logistic regression analyses. Results: DPP4a was increased in T2DM patients as compared with non-diabetic subjects (5855 ± 1632 vs 5208 ± 957 pmol/min/mL, p < 0.05). Clinical characteristics and echocardiographic parameters assessing LV morphology were similar across DPP4a tertiles in T2DM patients. However, prevalence of LVD progressively increased across incremental DPP4a tertiles (13%, 39% and 71%, all p < 0.001). Multivariate regression analysis confirmed the independent associations of DPP4a with LVD in T2DM patients (p < 0.05). Similarly, multiple logistic regression analysis showed that an increase of 100 pmol/min/min plasma DPP4a was independently associated with an increased frequency of LVD with an adjusted odds ratio of 1.10 (95% CI, 1.04 to 1.15, p = 0.001). Conclusions: An excessive activity of circulating DPP4 is independently associated with subclinical LVD in T2DM patients. Albeit descriptive, these findings suggest that DPP4 may be involved in the mechanisms of LVD in T2DM

Estudio petrográfico de las rocas volcánicas cenozoicas en el sur del Perú y sus implicancias con la mineralización

Las rocas volcánicas que afloran en el límite de la Cordillera Occidental y Altiplano en el Sur del Perú (Fig. 1), entre las localidades de Sibayo, Tisco, Condoroma y Ocuviri forman parte del volcanismo Eoceno al Mioceno (Klinck et al., 1996) y fueron emitidos por cuatro periodos de actividad volcánica denominados Tacaza, Palca, Sillapaca, Barroso Inferior (Cereceda et al., 2010). Además, existe una relación entre el control estructural y la formación de ocurrencias minerales en el emplazamiento del volcanismo de los periodos Tacaza y Sillapaca (Cerpa et al., 2011; Aguilar et al., 2010). El objetivo de este trabajo se centra en realizar una caracterización petrográfica de los periodos volcánicos Tacaza (30-24 Ma) y Sillapaca (16-10 Ma). En el periodo volcánico Tacaza, los centros volcánicos Cotacota y Ajopichaca no están asociados a ocurrencias minerales significativas, en cambio los centros volcánicos Acocunca y Choquepirhua presentan ocurrencias de Ag-Pb-Zn (Cu). En el periodo volcánico Sillapaca, los centros volcánicos Turputa y Machocondori hospedan yacimientos de alta sulfuración (Au-Ag), en tanto que los centros volcánicos Huishuillane y Tacamani están relacionados a ocurrencias de Cu-Ag-Zn. Por lo cual la finalidad es establecer una relación entre la textura microscópica con la mineralización asociada a estos períodos volcánicos

COVID-19 testing, infection, and vaccination among deported Mexican migrants: Results from a survey on the Mexico-U.S. border

BackgroundMigrants detained and held in immigration and other detention settings in the U.S. have faced increased risk of COVID-19 infection, but data on this population is scarce. This study sought to estimate rates of COVID-19 testing, infection, care seeking, and vaccination among Mexican migrants detained by U.S. immigration authorities and forcibly returned to Mexico.MethodsWe conducted a cross-sectional probability survey of Mexican migrants deported from the U.S. to three Mexican border cities: Tijuana, Ciudad Juárez, and Matamoros (N = 306). Deported migrants were recruited at Mexican migration facilities after being processed and cleared for departure. A two-stage sampling strategy was used. Within each city, a selection of days and shifts were selected during the operating hours of these deportation facilities. The probability of selection was proportional to the volume of migrants deported on each day of the month and during each time period. During the selected survey shifts, migrants were consecutively approached, screened for eligibility, and invited to participate in the survey. Survey measures included self-reported history of COVID-19 testing, infection, care seeking, vaccination, intentions to vaccinate, and other prevention and risk factors. Weighted data were used to estimate population-level prevalence rates. Bivariate tests and adjusted logistic regression models were estimated to identify associations between these COVID-19 outcomes and demographic, migration, and contextual factors.ResultsAbout 84.1% of migrants were tested for COVID-19, close to a third were estimated to have been infected, and, among them, 63% had sought care for COVID-19. An estimated 70.1% had been vaccinated against COVID-19 and, among those not yet vaccinated, 32.5% intended to get vaccinated. Close to half (44.3%) of respondents had experienced crowdedness while in detention in the U.S. Socio-demographic (e.g. age, education, English fluency) and migration-related (e.g. type of detention facility and time in detention) variables were significantly associated with COVID-19 testing, infection, care seeking, and vaccination history. Age, English fluency, and length of detention were positively associated with testing and vaccination history, whereas detention in an immigration center and length of time living in the U.S. were negatively related to testing, infection, and vaccination history. Survey city and survey quarter also showed adjusted associations with testing, infection, and vaccination history, reflecting potential variations in access to services across geographic regions and over time as the pandemic unfolded.ConclusionThese findings are evidence of increased risk of COVID-19 infection, insufficient access to testing and treatment, and missed opportunities for vaccination among Mexican migrants detained in and deported from the U.S. Deportee receiving stations can be leveraged to reduce disparities in testing and vaccination for deported migrants. In addition, decarceration of migrants and other measures informed by public health principles must be implemented to reduce COVID-19 risk and increase access to prevention, diagnostic, and treatment services among this underserved population

Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice:Relevance to Psychotic Disorders

BACKGROUND: Kynurenine 3-monooxygenase converts kynurenine to 3-hydroxykynurenine, and its inhibition shunts the kynurenine pathway-which is implicated as dysfunctional in various psychiatric disorders-toward enhanced synthesis of kynurenic acid, an antagonist of both α7 nicotinic acetylcholine and N-methyl-D-aspartate receptors. Possibly as a result of reduced kynurenine 3-monooxygenase activity, elevated central nervous system levels of kynurenic acid have been found in patients with psychotic disorders, including schizophrenia. METHODS: In the present study, we investigated adaptive-and possibly regulatory-changes in mice with a targeted deletion of Kmo (Kmo-/-) and characterized the kynurenine 3-monooxygenase-deficient mice using six behavioral assays relevant for the study of schizophrenia. RESULTS: Genome-wide differential gene expression analyses in the cerebral cortex and cerebellum of these mice identified a network of schizophrenia- and psychosis-related genes, with more pronounced alterations in cerebellar tissue. Kynurenic acid levels were also increased in these brain regions in Kmo-/- mice, with significantly higher levels in the cerebellum than in the cerebrum. Kmo-/- mice exhibited impairments in contextual memory and spent less time than did controls interacting with an unfamiliar mouse in a social interaction paradigm. The mutant animals displayed increased anxiety-like behavior in the elevated plus maze and in a light/dark box. After a D-amphetamine challenge (5 mg/kg, intraperitoneal), Kmo-/- mice showed potentiated horizontal activity in the open field paradigm. CONCLUSIONS: Taken together, these results demonstrate that the elimination of Kmo in mice is associated with multiple gene and functional alterations that appear to duplicate aspects of the psychopathology of several neuropsychiatric disorders