Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach

Background: To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) “black-box” approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). Methods: Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients’ attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/ pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. Results: Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians’ decision pathways to diagnose AMD. C Conclusions: Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support

Artificial neural network based identification of environmental bacteria by gas-chromatographic and electrophoretic data

Chemotaxonomic identification techniques are powerful tools for environmental micro-organisms, for which poor diagnostic schemes are available. Whole cellular fatty acid methyl esters (FAME) content is a stable bacterial profile, the analysis method is rapid, cheap, simple to perform and highly automated. Whole-cell protein is an even more powerful tool because it yields information at or below the species level. The description of new species and genera and subsequent continuous rearrangement provide large amounts of data, resulting in large databases. In order to set up suitable software tools to work on such large databases artificial neural network (ANN) based programs have been used to classify and identify marine bacteria at genus and species levels, starting from the fatty acid profiles and protein profiles respectively.We analysed 50 certified strains belonging to Halomonas, Marinomonas, Marinospirillum, Oceanospirillum and Pseudoalteromonas genera. Both supervised and unsupervised ANNs provide a correct classification of the marine strains analyzed. Moreover, a set of 73 marine fresh isolates were used as an example of identification using ANNs. We propose supervised and unsupervised ANNs as a reliable tool for classification of bacteria by means of their FAME and of whole-protein analyse and as a sound basis for a comprehensive artificial intelligence based system for polyphasic taxonom

Great auricular nerve preservation in parotid surgery: rationale 3 and long-term results insights

Great auricular nerve (GAN) is frequently sacrificed during parotid surgery. GAN preservation during parotidectomy is advised to avoid complications such as sensitive disorders, but debate still exists. In this study, our experience is reported on the matter. From a cohort of 173 parotidectomies carried out in the period 2005–2010, we studied 60 patients: 20 patients in which we preserved only the posterior branch of GAN (group A), 20 patients in which we preserved also the lobular branch (group B) and 20 patients in which the main trunk of GAN was sectioned (group C); we evaluated tactile sensitivity in all the skin supplied by GAN at 1 week, 1 month, 6 months and 1 year after surgery. Group B is the best in terms of loss and recovery of sensitivity after 1-year post-surgery, followed closely by group A, on the contrary group C confirmed to be the worst. Results suggest that saving as many branches of the GAN as possible during parotid surgery could be useful for reducing hypo-disestesia. Preserving posterior and lobular branches of the GAN, when possible, improves the sensitivity of the preauricular area with better quality of life for the patient

Training and mobility: a priority for the Organisation of the European Cancer Institutes. How a national mobility initiative could enhance EU cooperation in cancer research contributing to the development of an European Research Area: the example of the Italian Comprehensive Cancer Centers’ Network

It is widely recognized that productivity gains, sustained economic growth and employment are largely determined by technological progress, innovation and human capital. The 2000 Lisbon strategy to make Europe a competitive knowledge-based economy by 2010 and, more specifically, the Barcelona objectives agreed upon in 2002 to increase R&D investment in the EU to approach 3% of GDP, ensuring that there are sufficient human resources for research, are a preliminary step in this direction. If we want to reach this goal we have to succeed in retaining the best researchers, creating the right environment where they can perform their activities and develop their careers. To this aim the Organization of European Cancer Institutes (OECI) has set up a working group on Education and Training with the mandate to encourage continuing education in cancer research and applications and to verify the feasibility to promote mobility programs inside the network and in association with industries. Until now only few OECI training programs have been launched and a full mobility program has not been developed yet due to limited budget resources. The Italian Network of Comprehensive Cancer Centers, Alleanza Contro il Cancro, has planned the launch of a mobility program awarding 70 annual fellowships over a period of 36 months. This program, which will be open to the world research community, could represent a first interaction through mobility among the members of the OECI network also involving industries. The program is a tangible approach to sustain the translational process needed for the development of an European Research Area in the field of cancer and its related biomedical disciplines, thus providing a practical answer to the 2005 renewed Lisbon Strategy

Forward subtractive libraries containing genes transactivated by dexamethasone in ataxia-telangiectasia lymphoblastoid cells

Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder caused by biallelic mutations in the Ataxia Telangiectasia-mutated gene. A-T shows a complex phenotype ranging from early-onset progressive neurodegeneration to immunodeficiencies, high incidence of infections, and tumors. Unfortunately, no therapy is up to now available for treating this condition. Recently, the short term treatment of ataxia-telangiectasia patients with glucocorticoids was shown to improve their neurological symptoms and possibly reverse cerebellar atrophy. Thus, corticosteroids represent an attractive approach for the treatment of this neurodegenerative disease. However, the molecular mechanism involved in glucocorticoid action in A-T is yet unknown. The aim of our work is to construct cDNA libraries containing those genes which are transactivated by the glucocorticoid analogue, dexamethasone, in A-T human cells. For this purpose, suppression subtractive hybridization has been performed on ATM-null lymphoblastoid cell transcriptome extracted following drug administration. Annotation of whole genes contained in the libraries has been obtained by coupling subtractive hybridization with microarray analysis. Positive transcripts have been validated by quantitative PCR. Through in silico analyses, identified genes have been classified on the basis of the pathway in which they are involved, being able to address signaling required for dexamethasone action. Most of the induced transcripts are involved in metabolic processes and regulation of cellular processes. Our results can help to unravel the mechanism of glucocorticoid action in the reversion of A-T phenotype. Moreover, the induction of a specific region of the ATM transcript has been identified as putative biomarker predictive of dexamethasone efficacy on ataxic patients

Valor pronóstico del péptido natriurético cerebral y la troponina I en la tromboembolia pulmonar de riesgo moderado y alto

Background Brain natriuretic peptide (BNP) and troponins are useful markers for risk stratification in pulmonary embolism (PE). However, it is not clear which of the two biomarkers has better association with the clinical severity of this condition. Objective The aim of this study was to assess both biomarkers in moderate and high risk populations. Methods A prospective study was undertaken to analyze all patients diagnosed with PE who had positive troponin I (TI) or BNP levels. An echocardiogram within the first 24 hours and clinical follow up during hospitalization were performed on these patients. A composite endpoint of death, recurrent PE, shock, hypotension, mechanical respiratory assistance and thrombolytic therapy was established. The association of both serum markers with the described events was assessed. Results Seventy one consecutive patients were included in this study. Patients with moderate or severe right ventricular dysfunction had higher BNP levels (661 pg/ml (420-1113) vs. 316 pg/ml (129-570) p=0.002) without significant difference in TI levels (0.115 ng/ml (0.015-0.345) vs. 0.24 ng/ml (0.076-0.58) p=0.0788). BNP levels were higher in patients with composite endpoint [604 pg/ml (370-934) vs. 316 pg/ml (148-900) p=0.042], whereas no similar association was found for TI [0.12 ng/ml (0.037-0.48) vs. 0.13 ng/ml (0.07-0.41) p=0.46]. Conclusions BNP showed higher values in patients with right ventricular dysfunction and composite endpoint, indicating its greater sensitivity to identify patients with more severe clinical involvement.Introducción El péptido natriurético cerebral (BNP) y las troponinas son marcadores útiles para la estratificación de la tromboembolia pulmonar (TEP), pero se desconoce cuál tiene mejor asociación con la gravedad del cuadro. Objetivo Evaluar ambos marcadores en forma comparativa dentro de una población de riesgo moderado y alto. Material y métodos Se elaboró un registro prospectivo de los pacientes con diagnóstico de TEP que presentaran troponina I (TI) o BNP positivos. Se realizó un ecocardiograma en las primeras 24 horas y seguimiento clínico en la internación. Se estableció un punto combinado de muerte, recurrencia de TEP, shock, hipotensión arterial, asistencia respiratoria mecánica y uso de trombolíticos. Se buscó la asociación entre ambos marcadores y los eventos descriptos. Resultados Se incluyeron 71 pacientes consecutivos. Los pacientes con disfunción moderada o grave del ventrículo derecho presentaron niveles mayores de BNP [661 pg/ml (420-1113) vs. 316 pg/ml (129-570); p = 0,002], sin diferencias en los niveles de TI [0,115 ng/ml (0,015-0,345) vs. 0,24 ng/ml (0,076-0,58); p = 0,0788]. Los niveles de BNP fueron mayores en los que presentaron el punto combinado [604 pg/ml (370-934) vs. 316 pg/ml (148-900); p = 0,042], mientras que con la TI no ocurrió lo mismo [0,12 ng/ml (0,037-0,48) vs. 0,13 ng/ml (0,07-0,41); p = 0,46]. Conclusiones El BNP tuvo valores más elevados en pacientes con disfunción ventricular significativa y en los que tuvieron el punto combinado. Este hallazgo podría reflejar una mayor utilidad del BNP respecto de la TI para identificar a los pacientes con mayor compromiso clínico

Radiological and clinical difficulties in the management of chronic maxillary sinusitis in β Thalassemic paediatric patients

Introduction: Beta thalassemia is a blood dyscrasia that caused a marked expansion of active marrow spaces and extramedullary haematopoiesis results. In these patients various alterations and abnormalities affects different body areas, including increased risk of sinusitis. The marrow expansion in the facial bones results in delay in pneumatisation of the sinuses, overgrowth of the maxillae, and forward displacement of the upper incisors with skeletal deformities.In current literature, maxillary sinuses are not deeply evaluated by CT scan studies in these kind of patients.The aim of our study was to investigate the presence of maxillary sinuses abnormalities by the use of CT in patients with beta-thalassemia major and to compare these findings with a control group free from this disease.Materials and methods: A retrospective analysis of 22 paediatric patients with beta-thalassemia major and 22 control subjects without sinonasal diseases was performed. CT was done using a 64-multidetector-row CT scanner without contrast injection, obtained in axial plane using thin-slice technique. Evaluated parameters were: bone thickness of the lateral and anterior wall, density and volume of the maxillary sinuses.Results: Significant difference was found between the study group and control group in the evaluation of all the parameters examined. The maxillary sinus of beta thalassemic patients was smaller respect of controls, the bone was more dense and thick in the side and anterior wall. Beta-thalassemic patients have a relative risk of 2.87 to develop a maxillary sinusitis.Discussion: In these patients there is an increased incidence of sinonasal infections due to the abnormal development of cranio facial skeleton. These bone alterations might confuse the physicians and lead to an increased rate of sinusitis diagnoses. (C) 2016 Elsevier Ireland Ltd. All rights reserved

Level of Human Immunodeficiency Virus DNA in Peripheral Blood Mononuclear Cells Correlates with Efficacy of Antiretroviral Therapy

A novel colorimetric assay was developed and validated for accurate quantitation of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs). We tested 318 sequential samples from 56 subjects, 53 of whom were undergoing dual or triple therapy. Patients were considered responders when viremia levels were below 5,000 HIV RNA copies/ml. The mean DNA copy numbers for untreated and responder subjects were similar (72 and 75, respectively), while it was 4.54-fold higher for nonresponders (339). This report provides strong evidence that HIV DNA levels in PBMCs correlate with therapeutic efficacy and suggests that DNA quantitation is a useful tool to monitor the decay of the HIV reservoir toward disease remission, especially when viremia is undetectable