Field testing, validation and optimization report

The COMMON SENSE project has been designed and planned in order to meet the general and specific scientific and technical objectives mentioned in its Description of Work (page 77). As the overall strategy, the 11 work packages (WPs) of the work plan were grouped into 3 key phases: (1) RD basis for cost-effective sensor development , (2) Sensor development, sensor web platform and integration, and (3) Field testing. In the first two phases, partners involved in WP1 and WP2 have provided a general understanding and integrated basis for a cost effective sensors development. Within the following WPs 4 to 8 the new sensors were created and integrated into different identified platforms. During the third phase of field testing (WP9), partners have deployed precompetitive prototypes at chosen platforms (e.g. research vessels, oil platforms, buoys and submerged moorings, ocean racing yachts, drifting buoys). Starting from August 2015 (month 22; task 9.2), these platforms have allowed the partnership to test the adaptability and performance of the in-situ sensors and verify if the transmission of data is properly made, correcting deviations. In task 9.1 all stakeholders identified in WP2 have been contacted in order to agree upon a coordinated agenda for the field testing phase for each of the platforms. Field testing procedures (WP2) and deployment specificities, defined during sensor development in WPs 4 to 8, have been closely studied by all stakeholders involved in field testing activities in order for everyone to know their role, how to proceed and to provide themselves with the necessary material and equipment (e.g. transport of instruments). All this information have provided the basis for designing and coordinating field testing activities. Subsequently, the available new sensors have been tested since August 2015 till mid-October of the current year (2016) as part of task 9.2, following the indications defined in D9.1, such as the intercomparison of the new sensors with commercial ones, when possible. The availability of new sensors was quite different in time starting with the first tests in September and October 2015 on noise, nutrient and heavy metals sensors and closing with pCO2 in late September 2016. Sensors are technically fully described in the deliverables of WPs 3 to 8 and are here just mentioned where necessary. For further details, please consider those reports. Objectives and rationale The protocols prepared in D9.1 have been verified during the field testing activities of the innovative sensors on platforms. These can be summarized into 3 categories: (1) Research vessels (regular cruises); (2) Fixed platforms; (3) Ocean racing yachts. An exhaustive analysis of the different data obtained during field testing activities has been carried on in order to set possible optimization actions for prototypes design and performances. The data from each platform have been analyzed to verify limits and optimal installations or possible improvements. Finally a set of possible optimization actions has been defined. Data and observations collected during the course of field testing have been used to iteratively optimize the design and performance of the precompetitive prototypes

Protocols for the field testing

The COMMON SENSE project has been designed and planned in order to meet the general and specific scientific and technical objectives mentioned in its Description of Work (page 77). In an overall strategy of the work plan, work packages (11) can be grouped into 3 key phases: (1) RD basis for cost-effective sensor development, (2) Sensor development, sensor web platform and integration, and (3) Field testing. In the first two phases WP1 and WP2 partners have provided a general understanding and integrated basis for a cost effective sensors development. Within the following WPs 4 to 8 the new sensors are created and integrated into different identified platforms. During the third phase 3, characterized by WP9, partners will deploy precompetitive prototypes at chosen platforms (e.g. research vessels, oil platforms, buoys and submerged moorings, ocean racing yachts, drifting buoys). Starting from August 2015 (month 22; task 9.2), these platforms will allow the partnership to test the adaptability and performance of the in-situ sensors and verify if the transmission of data is properly made, correcting deviations. In task 9.1 all stakeholders identified in WP2, and other relevant agents, have been contacted in order to close a coordinated agenda for the field testing phase for each of the platforms. Field testing procedures (WP2) and deployment specificities, defined during sensor development in WPs 4 to 8, are closely studied by all stakeholders involved in field testing activities in order for everyone to know their role, how to proceed and to provide themselves with the necessary material and equipment (e.g. transport of instruments). All this information will provide the basis for designing and coordinating field testing activities. Type and characteristics of the system (vessel or mooring, surface or deep, open sea or coastal area, duration, etc.), used for the field testing activities, are planned comprising the indicators included in the above-mentioned descriptors, taking into account that they must of interest for eutrophication, concentration of contaminants, marine litter and underwater noise. In order to obtain the necessary information, two tables were realized starting from the information acquired for D2.2 delivered in June 2014. One table was created for sensor developers and one for those partners that will test the sensors at sea. The six developers in COMMON SENSE have provided information on the seven sensors: CEFAS and IOPAN for underwater noise; IDRONAUT and LEITAT for microplastics; CSIC for an innovative piro and piezo resistive polymeric temperature and pressure and for heavy metal; DCU for the eutrophication sensor. This information is anyway incomplete because in most cases the novel sensors are still far to be ready and will be developed over the course of COMMON SENSE. So the sensors cannot be clearly designed yet and, consequently, technical characteristics cannot still be perfectly defined. This produces some lag in the acquired information and, consequently, in the planning of their testing on specific platforms that will be solved in the near future. In the table for Testers, partners have provided information on fifteen available platforms. Specific answers have been given on number and type of sensors on each platforms, their availability and technical characteristics, compatibility issues and, very important when new sensors are tested, comparative measurements to be implemented to verify them. Finally IOPAN has described two more platforms, a motorboat not listed in the DoW, but already introduced in D2.2, and their oceanographic buoy in the Gdansk Bay that was previously unavailable. The same availability now is present for the OBSEA Underwater observatory from CSIC, while their Aqualog undulating mooring is still not ready for use. In the following months, new information on sensors and platforms will be provided and the planning of testing activities will improve. Further updates of this report will be therefore necessary in order to individuate the most suitable platforms to test each kind of sensor. Objectives and rationale The objective of deliverable 9.1 is the definition of field testing procedures (WP2), the study of deployment specificities during sensor development work packages (from WP4 to WP8) and the preparation of protocols. This with the participation of all stakeholders involved in field testing activities in order for everyone to know their role, how to proceed and to provide themselves with the necessary material and equipment

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Transcriptional Shift Identifies a Set of Genes Driving Breast Cancer Chemoresistance

Background Distant recurrences after antineoplastic treatment remain a serious problem for breast cancer clinical management, which threats patients’ life. Systemic therapy is administered to eradicate cancer cells from the organism, both at the site of the primary tumor and at any other potential location. Despite this intervention, a significant proportion of breast cancer patients relapse even many years after their primary tumor has been successfully treated according to current clinical standards, evidencing the existence of a chemoresistant cell subpopulation originating from the primary tumor.Methods/Findings To identify key molecules and signaling pathways which drive breast cancer chemoresistance we performed gene expression analysis before and after anthracycline and taxane-based chemotherapy and compared the results between different histopathological response groups (good-, mid- and bad-response), established according to the Miller & Payne grading system. Two cohorts of 33 and 73 breast cancer patients receiving neoadjuvant chemotherapy were recruited for whole-genome expression analysis and validation assay, respectively. Identified genes were subjected to a bioinformatic analysis in order to ascertain the molecular function of the proteins they encode and the signaling in which they participate. High throughput technologies identified 65 gene sequences which were over-expressed in all groups (P ≤ 0·05 Bonferroni test). Notably we found that, after chemotherapy, a significant proportion of these genes were over-expressed in the good responders group, making their tumors indistinguishable from those of the bad responders in their expression profile (P ≤ 0.05 Benjamini-Hochgerg`s method).Conclusions These data identify a set of key molecular pathways selectively up-regulated in post-chemotherapy cancer cells, which may become appropriate targets for the development of future directed therapies against breast cancer.Thanks are due to the Consejería de Economia, Innovación y Ciencia (CEIC) from the Junta de Andalucía and Fondo Europeo de Desarrollo Regional (FEDER)/Fondo de Cohesión Europeo (FSE) to financial support through the Programa Operativo FEDER/FSE de Andalucía 2007-2013 and the research project CTS-5350. The authors also acknowledge financial support by the PN de I+D+i 2006-2009/ISCIII/Ministerio de Sanidad, Servicios Sociales e Igualdad (Spain) and Fondo Europeo de Desarrollo Regional (FEDER) from the European Union, through the research project PI06/90388

Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life.

BACKGROUND: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate immune responses modulate the risk of malaria during the first year of life. METHODS: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial (NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria infections during pregnancy and infants' clinical malaria episodes detected during the first year of life were recorded. Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations and ratios of TLR-mediated cytokine responses relative to background control were analyzed. RESULTS: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group. However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life. CONCLUSIONS: These findings indicate that past placental malaria has a profound effect on fetal immune system and that the differential alterations of innate immune responses by PME categories might drive heterogeneity between individuals to clinical malaria susceptibility during the first year of life

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand

Objective: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. Design: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. Methods: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. Results: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. Conclusion: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch