Evolving Recursive Programs using Non-recursive Scaffolding

Genetic programming has proven capable of evolving solutions to a wide variety of problems. However, the successes have largely been with programs without iteration or recursion; evolving recursive programs has turned out to be particularly challenging. The main obstacle to evolving recursive programs seems to be that they are particularly fragile to the application of search operators: a small change in a correct recursive program generally produces a completely wrong program. In this paper, we present a simple and general method that allows us to pass back and forth from a recursive program to an associated non-recursive program. Finding a recursive program can be reduced to evolving non-recursive programs followed by converting the optimum non-recursive program found to the associated optimum recursive program. This avoids the fragility problem above, as evolution does not search the space of recursive programs. We present promising experimental results on a test-bed of recursive problems

Monolithic integration of Giant Magnetoresistance (GMR) devices onto standard processed CMOS dies

Giant Magnetoresistance (GMR) based technology is nowadays the preferred option for low magnetic fields sensing in disciplines such as biotechnology or microelectronics. Their compatibility with standard CMOS processes is currently investigated as a key point for the development of novel applications, requiring compact electronic readout. In this paper, such compatibility has been experimentally studied with two particular non-dedicated CMOS standards: 0.35 μm from AMS (Austria MicroSystems) and 2.5 μm from CNM (Centre Nacional de Microelectrònica, Barcelona) as representative examples. GMR test devices have been designed and fabricated onto processed chips from both technologies. In order to evaluate so obtained devices, an extended characterization has been carried out including DC magnetic measurements and noise analysis. Moreover, a 2D-FEM (Finite Element Method) model, including the dependence of the GMR device resistance with the magnetic field, has been also developed and simulated. Its potential use as electric current sensors at the integrated circuit level has also been demonstrated

Data-driven prescription patterns in patients under maintenance treatment for respiratory diseases from the Portuguese prescription database

We aimed to identify prescription patterns in respiratory patients using an unsupervised (data-driven) method, in a random sample of patients aged >14 years (n=8799), retrieved from the Portuguese Electronic Medical Prescription database. Respiratory patients were defined if >2 packs of maintenance treatment for respiratory diseases were prescribed in 2016. We analysed all the prescriptions (n=39810) for respiratory diseases and exacerbations by medication type. Two-step clustering was based on the presence of ICS, LABA, LTRA, LAMA, LABA, SABA, SAMA and on the speciality of prescriber.info:eu-repo/semantics/publishedVersio

Unsupervised algorithms to identify potential under-coding of secondary diagnoses in hospitalisations databases in Portugal

Quantifying and dealing with lack of consistency in administrative databases (namely, under-coding) requires tracking patients longitudinally without compromising anonymity, which is often a challenging task. This study aimed to (i) assess and compare different hierarchical clustering methods on the identification of individual patients in an administrative database that does not easily allow tracking of episodes from the same patient; (ii) quantify the frequency of potential under-coding; and (iii) identify factors associated with such phenomena. We analysed the Portuguese National Hospital Morbidity Dataset, an administrative database registering all hospitalisations occurring in Mainland Portugal between 2011–2015. We applied different approaches of hierarchical clustering methods (either isolated or combined with partitional clustering methods), to identify potential individual patients based on demographic variables and comorbidities. Diagnoses codes were grouped into the Charlson an Elixhauser comorbidity defined groups. The algorithm displaying the best performance was used to quantify potential under-coding. A generalised mixed model (GML) of binomial regression was applied to assess factors associated with such potential under-coding. We observed that the hierarchical cluster analysis (HCA) + k-means clustering method with comorbidities grouped according to the Charlson defined groups was the algorithm displaying the best performance (with a Rand Index of 0.99997). We identified potential under-coding in all Charlson comorbidity groups, ranging from 3.5% (overall diabetes) to 27.7% (asthma). Overall, being male, having medical admission, dying during hospitalisation or being admitted at more specific and complex hospitals were associated with increased odds of potential under-coding. We assessed several approaches to identify individual patients in an administrative database and, subsequently, by applying HCA + k-means algorithm, we tracked coding inconsistency and potentially improved data quality. We reported consistent potential under-coding in all defined groups of comorbidities and potential factors associated with such lack of completeness. Our proposed methodological framework could both enhance data quality and act as a reference for other studies relying on databases with similar problems.info:eu-repo/semantics/publishedVersio

Adult Asthma Scores—Development and Validation of Multivariable Scores to Identify Asthma in Surveys

Background One of the questions in epidemiology is the identification of adult asthma in studies. Objective To develop and validate multivariable scores for adult asthma identification in epidemiological studies and to explore cutoffs to rule in/rule out asthma, compared with asthma diagnosed by a physician after clinical examination and diagnostic tests, blinded to the self-administered questions. Methods We analyzed data (n = 711 adults) from a nationwide population-based study. The predictors were self-administered questions identified in a literature review (the Adult Asthma Epidemiological Score [A2 score]) and from the Global Allergy and Asthma Network of Excellence (GA2LEN) questionnaire (the GA2LEN Asthma Epidemiological Score [GA2LEN score]). Scores were developed using exploratory factor analysis. Internal consistency, discriminative power, and diagnostic accuracy were assessed. Results The A2 score comprises 8 questions (including “Did a physician confirm you had asthma?”) and the GA2LEN score comprises 6 questions (including “Have you ever had asthma?”). Both had high Cronbach α (0.89 and 0.85, respectively, for the A2 score and the GA2LEN score) and good area under the receiver-operating characteristic curve (90.4% and 89.0%). The scoring is the sum of positive answers. Asthma is present (rule in) for scores of 4 or more (specificity, 99.2%; PPV, 93.3% and 91.7%; accuracy, 89.4% and 87.4%, respectively, for the A2 score and the GA2LEN score). Asthma is excluded (rule out) for A2 scores of 0 to 1 and a GA2LEN score of 0 (sensitivity, 93.1%; NPV, 98.2% and 98.0%; accuracy 89.4% and 82.8%, respectively, for the A2 score and the GA2LEN score). Conclusions These practical scores can be used to rule in/rule out asthma in epidemiological studies and clinical screening/triage settings. They may help physicians in primary care or other specialties to screen patients with asthma using a simple score with a high level of discrimination and to identify the best candidates to be referred for a diagnostic workup. Moreover, their use may contribute to reducing the inconsistencies of operational definitions of asthma across studies and surveys.info:eu-repo/semantics/publishedVersio

Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

Trial Design: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. Methods: Participants: Antiretroviral naive adult males with CD4 count >= 350 cells/mm(3). Interventions: Patients were randomised to receive thalidomide 200 mg QD for 3 weeks (Thalidomide group) or not (Control group) and followed for 48 weeks. Objective: We hypothesized that short-term Thalidomide use would reduce HIV related inflammation and HIV replication among antiretroviral naive HIV infected individuals. Outcome: Viral loads, CD4/CD8 counts, ultra-sensitive C-reactive protein (US-CRP), cell activation markers, and plasma lipopolysaccharide (LPS) were analyzed. Randomisation: Unrestricted randomisation. Blinding: No blinding was used. Results: Numbers randomised: Thirty recruited individuals were randomised to Thalidomide (16 patients) or Control (14 patients) groups. Recruitment: Patients were recruited from April 2011 to January 2013. Outcome: Viral loads remained stable in both groups. During thalidomide treatment, a decrease in CD4/CD8 ratio (p = 0.04), a decrease in CD4 count (p = 0.04), an increase in cell activation calculated by the percentage of CD38 (+)/HLA-DR+ CD8 cells (p < 0.05) and an increase in US-CRP (p < 0.01) were observed in the Thalidomide group, with all parameters returning to baseline levels after thalidomide interruption. We confirmed that thalidomide increased HIV replication in vitro of 6 of 7 samples from long-term antiretroviral suppressed individuals. Harms: No class 3/4 adverse events occurred. Conclusions: Short-termuse of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4(+) cell count without changes to the CD8(+) cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication. (C) 2017 The Authors. Published by Elsevier B.V.Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)Univ Fed São Paulo, Lab Retrovirol, São Paulo, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Interdisciplinar Pesquisas Med, Rio De Janeiro, BrazilSecretaria Municipal Saude Antonio Ribeiro Neto, Rio De Janeiro, BrazilOncohiv, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, BrazilInst Fed Educ Ciencia & Tecnol Rio de Janeiro IF, Rio De Janeiro, BrazilUniv Fed São Paulo, Lab Retrovirol, São Paulo, BrazilFAPESP: 04/15856-9Web of Scienc

Lamivudine’s hypersensitivity in an HIV infected patient: case report

Importância do problema: Relatar um caso de hipersensibilidade à lamivudina, droga considerada segura e antirretroviral indicado como de primeira linha para início de tratamento para pacientes infectados pelo HIV. Comentários: É relatado o caso de paciente infectada pelo HIV que evoluiu com farmacodermia associada à terapia antirretroviral (TARV) utilizando tenofovir, lamivudina e efavirenz. Inicialmente, a hipersensibilidade foi atribuída ao efavirenz, pela maior incidência de eventos desta natureza com este medicamento e este foi substituído por fosamprenavir/ ritonavir. Apesar da substitui- ção, paciente desenvolveu síndrome de Stevens-Johnson. Foi hospitalizada e iniciou novo esquema, com introdução de droga a droga, com atazanavir/ritonavir, seguido de zidovudina e lamivudina, desenvolvendo manifestação de eritema multiforme após a última droga, sendo esta considerada a responsá- vel pela hipersensibilidadeRelevance: To report a case of hypersensitivity to lamivudine, a medicine that is considered safe and is indicated as part of the initial therapy for HIV infected patients. Comments: It is reported the evolution of an HIV patient who developed a drug eruption due to the following antirretroviral therapy: tenofovir, lamivudine and efavirenz. It initially was attributed to efavirenz, due to its higher incidence in these adverse reactions and it was replaced by fosamprenavir/ritonavir. In spite of the replacement, the patient developed Stevens-Johnson's Syndrome. She was hospitalized and began a new therapy with atazanavir/ritonavir, followed by zidovudine and lamivudine and presented a drug reaction with the last one, which was considered to be the responsible for the hypersensitivit

The Role of Purinergic Signaling in the Pathophysiology of Perinatal Hypoxic-Ischemic Encephalopathy

Perinatal hypoxic-ischemic encephalopathy (HIE), known as birth asphyxia, remains a major contributor to poor neurodevelopmental outcomes including cerebral palsy and seizures. One striking feature of HIE injury is a delayed progression of neuronal degeneration that spreads over time from the most severely damaged areas outward into neighboring undamaged regions. There is increasing evidence that these lesions act as sites of origin for waves of spreading depression (SD), a wave of neuronal and glial depolarization, that progressively enlarge the brain lesions. While the pathophysiology of SD is still under debate, there is increasing evidence that purinergic receptors in conjunction with connexin and pannexin 1 channels are necessary for sustained propagation of the waves and neuroinflammation. This review intends to discuss the relative contribution of purinergic signaling and connexin and pannexin 1 channels to trigger and spread SD waves leading to the development of progressive brain lesions under conditions of perinatal HIE

Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts

We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance.(SFRH/BPD/115169/2016) funded by Fundação para a Ciência e Tecnologia (FCT); ERDF (European Regional Development Fund) through the operations: POCI-01-0145-FEDER-029130 ('mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases—generalisation and evaluation of gamification, peer support and advanced image processing technologies') cofunded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).info:eu-repo/semantics/publishedVersio

Structural and spectroscopic investigation of the charge-ordered, short-range ordered, and disordered phases of the Co3O2BO3 ludwigite

Charge ordering is prone to occur in crystalline materials with mixed-valence ions. It is presumably accompanied by a structural phase transition, with possible exceptions in compounds that already present more than one inequivalent site for the mixed-valence ions in the charge-disordered phase. In this work, we investigate the representative case of the homometallic Co ludwigite Co2+2Co3+O2BO3 (Pbam space group) with four distinct Co crystallographic sites [M1–M4] surrounded by oxygen octahedra. The mixed-valent character of the Co ions up to at least T=873 K is verified through x-ray absorption near-edge structure (XANES) experiments. Single crystal x-ray diffraction (XRD) and neutron powder diffraction (NPD) confirm that the Co ions at the M4 site are much smaller than the others at low temperatures, consistent with a Co3+ oxidation state at M4 and Co2+ at the remaining sites. The size difference between the Co ions in the M4 and M2 sites is continuously reduced upon warming above ≈370 K, indicating a gradual charge redistribution within the M4−M2−M4 (424) ladder in the average structure. Minor structural anomalies with no space group modification are observed near 475 and 495 K, where sharp phase transitions were previously revealed by calorimetry and electrical resistivity data. An increasing structural disorder, beyond a conventional thermal effect, is noted above ≈370 K, manifested by an anomalous increment of XRD Debye-Waller factors and broadened vibrational modes observed by Raman scattering. The local Co-O distance distribution, revealed by Co K-edge extended x-ray absorption fine structure (EXAFS) data and analyzed with an evolutionary algorithm method, is similar to that inferred from the XRD crystal structure below ≈370 K. At higher temperatures, the local Co-O distance distribution remains similar to that found at low temperatures, at variance with the average crystal structure obtained with XRD. We conclude that the oxidation states Co2+ and Co3+ are instantaneously well defined in a local atomic level at all temperatures, however the thermal energy promotes local defects in the charge-ordered configuration of the 424 ladders upon warming. These defects coalesce into a phase-segregated state within a narrow temperature interval (475<T<495 K). Finally, a transition at ≈500 K revealed by differential scanning calorimetry (DSC) in the iron ludwigite Fe3O2BO3 is discussed