Pre-vaccine rotavirus surveillance in Buenos Aires, Argentina. Characterization of an emergent G1P[8] strain associated to fatal cases in 2014.

Group A rotaviruses (RVA) are the most frequent etiological agents causing severe diarrhea in infants and surveillance of genotype, and genetic characteristics of circulating strains are necessary in order to evaluate vaccine programs. The objectives of this work were to describe G and P genotype from 2012 through 2014 in Buenos Aires, Argentina completing an overview of 19 years of genotype surveillance in our region and to characterize an emerging G1P[8] strain associated with severe cases and five fatalities in 2014. We performed genotyping by RT-PCR. The sequencing of several genes, phylogenetic analyses, and comparative epidemiological data were used to know the origin and phylogenetic relationships of the emerging G1P[8] strain. Along with this report, 19 years of continuous RVA genotype surveillance in Argentina in the pre-vaccine era was covered. During the last year of this surveillance, 2014, a significantly increased incidence of RVA associated gastroenteritis was related to the reemergence of G1P[8] strains, being these ones detected in low frequency in the last nine years. Interestingly, the patients affected were significantly older when compared with those from the last six seasons. Additionally, phylogenetic analysis of several genes infer that these G1P[8] strains were closely related to Asian strains circulating during 2012 and 2013. In addition to this, the suggested extra continental origin for the 2014 G1P[8] strains and the very low circulation of G1 type during nine years probably explain the increased incidence and severity in the gastroenteritis cases and the particular epidemiologic characteristics. In conclusion, this work gives us a whole panorama of the pre-vaccine era of the RVA molecular epidemiology in the most populated region of Argentina. In this way, this work inspires us to continue with this type of studies in the post-vaccination era.

Caracterización de Cepas de Virus Sincitial Respiratorio en el Gran Buenos Aires y Aspectos de su Diseminación / Characterization of Respiratory Syncytial Virus Strains in the Greater Buenos Aires and Spreading Aspects

INTRODUCCIÓN: El virus sincitial respiratorio (VSR) es el agente viral más frecuente de infecciones respiratorias agudas bajas (IRAB) en la primera infancia y el mayor responsable de las hospitalizaciones en el período invernal. OBJETIVOS: Describir las características de los brotes de VSR en la Zona Sanitaria VI de la provincia de Buenos Aires, establecer la diversidad de las cepas circulantes y realizar el análisis bioinformático y filogeográfico de las secuencias de la glicoproteína G. MÉTODOS: Se estudió a pacientes pediátricos internados con presentación compatible con IRAB durante dos picos epidémicos (2014-2015) en cuatro hospitales. Se recopilaron datos clínicos, demográficos y socio-sanitarios, y se detectaron patógenos virales en aspirados nasofaríngeos de estos pacientes por inmunofluorescencia (IF), obteniéndose la secuencia del gen de la proteína G en los VSR positivos. RESULTADOS: De 1296 casos estudiados, 317 fueron positivos para algún agente viral. De ellos, 266 (84%) fueron VSR positivos. Se hallaron asociaciones significativas entre las poblaciones positivas y negativas para VSR. Una tendencia al hacinamiento y vivienda precaria en los casos VSR positivos fue reflejada en los estudios filogeográficos. CONCLUSIONES: Los datos de firma molecular permitieron trazar orígenes y vías de diseminación del VSR. Esto ayuda a señalar zonas y situaciones de vulnerabilidad, estableciendo la población primaria blanco de planes de vacunación u otras medidas profilácticas.

INTRODUCTION: The respiratory syncytial virus (RSV) is the most frequent viral agent associated to acute lower respiratory infections (ALRIs) in early childhood, being the main responsible for hospitalizations during winter. OBJECTIVES: To describe the characteristics of RSV outbreaks in the Health Area VI of Buenos Aires Province, to establish the diversity of circulating strains and to perform a bioinformatic and phylogeographic analysis of glycoprotein G sequences. METHODS: Pediatric inpatients with ALRI-compatible x|presentation during two epidemic peaks (2014-2015) were studied in four hospitals. Clinical, demographic and socio-sanitary data were collected, viral pathogens were detected by immunofluorescence (IF), and the sequence of the G protein gene was obtained in the positive RSVs. RESULTS: From 1296 cases, 317 were positive for some viral agent and 266 (84%) out of these were RSV positive. Significant associations were found among the positive and negative populations for RSV. A trend towards overcrowding and precarious housing in positive RSV cases was reflected in phylogeographic studies. CONCLUSIONS: The molecular signature data allowed tracing origins and routes of RSV dissemination. This helps identify areas and situations of vulnerability, establishing the primary target population for vaccination plans or other prophylactic measures.

Unravelling respiratory syncytial virus outbreaks in Buenos Aires, Argentina: Molecular basis of the spatio-temporal transmission.

Respiratory syncytial virus (RSV) is the main viral cause of hospitalization due to acute lower respiratory tract infections in infants worldwide. Several vaccines against RSV are under research and development, which are about to be approved. We evaluated transmission patterns in different settings to determine age-specific vaccination targets from a viral perspective. We sequenced the G glycoprotein's ectodomain of a constant clinical sampling between two epidemic outbreaks in a limited geographical region and performed phylogeographic analyses. We described a spatio-temporal transmission between local strains, which were originated in the center of the analyzed area and then spread to others. Interestingly, that central area reported the highest population density of the region and also showed overcrowding. This information should be considered by public health systems to evaluate vaccination at all ages in those areas to decrease viral transmission and in lower density populations only susceptible children should be vaccinated.

System-Level Design of a 64-Channel Low Power Neural Spike Recording Sensor.

This paper reports an integrated 64-channel neural spike recording sensor, together with all the circuitry to process and configure the channels, process the neural data, transmit via a wireless link the information and receive the required instructions. Neural signals are acquired, filtered, digitized and compressed in the channels. Additionally, each channel implements an auto-calibration algorithm which individually configures the transfer characteristics of the recording site. The system has two transmission modes; in one case the information captured by the channels is sent as uncompressed raw data; in the other, feature vectors extracted from the detected neural spikes are released. Data streams coming from the channels are serialized by the embedded digital processor. Experimental results, including in vivo measurements, show that the power consumption of the complete system is lower than 330 µW.

A Low Noise Amplifier for Neural Spike Recording Interfaces.

This paper presents a Low Noise Amplifier (LNA) for neural spike recording applications. The proposed topology, based on a capacitive feedback network using a two-stage OTA, efficiently solves the triple trade-off between power, area and noise. Additionally, this work introduces a novel transistor-level synthesis methodology for LNAs tailored for the minimization of their noise efficiency factor under area and noise constraints. The proposed LNA has been implemented in a 130 nm CMOS technology and occupies 0.053 mm-sq. Experimental results show that the LNA offers a noise efficiency factor of 2.16 and an input referred noise of 3.8 µVrms for 1.2 V power supply. It provides a gain of 46 dB over a nominal bandwidth of 192 Hz-7.4 kHz and consumes 1.92 µW. The performance of the proposed LNA has been validated through in vivo experiments with animal models.

A 515 nW, 0-18 dB Programmable Gain Analog-to-Digital Converter for In-Channel Neural Recording Interfaces.

This paper presents a low-area low-power Switched-Capacitor (SC)-based Programmable-Gain Analog-to-Digital Converter (PG-ADC) suitable for in-channel neural recording applications. The PG-ADC uses a novel implementation of the binary search algorithm that is complemented with adaptive biasing techniques for power saving. It has been fabricated in a standard CMOS 130 nm technology and only occupies 0.0326 mm(2). The PG-ADC has been optimized to operate under two different sampling modes, 27 kS/s and 90 kS/s. The former is tailored for raw data conversion of neural activity, whereas the latter is used for the on-the-fly feature extraction of neural spikes. Experimental results show that, under a voltage supply of 1.2 V, the PG-ADC obtains an ENOB of 7.56 bit (8-bit output) for both sampling modes, regardless of the gain setting. The amplification gain can be programmed from 0 to 18 dB. The power consumption of the PG-ADC at 90 kS/s is 1.52 µW with a FoM of 89.49 fJ/conv, whereas at 27 kS/s it consumes 515 nW and obtains a FoM of 98.31 fJ/conv .

A low-power programmable neural spike detection channel with embedded calibration and data compression.

This paper reports a programmable 400 µm pitch neural spike recording channel, fabricated in a 130 nm standard CMOS technology, which implements amplification, filtering, digitization, analog spike detection plus feature extraction, and self-calibration functionalities. It can operate in two different output modes: 1) signal tracking, in which the neural signal is sampled and transmitted as raw data; and 2) feature extraction, in which the spikes of the neural signal are detected and encoded by piece-wise linear curves. Additionally, the channel offers a foreground calibration procedure in which the amplification gain and the passband of the embedded filter can be self-adjusted. The amplification stage obtains a noise efficiency factor of 2.16 and an input referred noise of 2.84 µVrms over a nominal bandwidth of 167 Hz-6.9 kHz. The channel includes a reconfigurable 8-bit analog-to-digital converter combined with a 3-bit controlled programmable gain amplifier for adjusting the input signal to the full scale range of the converter. This combined block achieves an overall energy consumption per conversion of 102 fJ at 90 kS/s. The energy consumed by the circuit elements which are strictly related to the digitization process is 14.12 fJ at the same conversion rate. The complete channel consumes 2.8 µW at 1.2 V voltage supply when operated in the signal tracking mode, and 3.1 µW when the feature extraction mode is enabled.