Formamide as the main building block in the origin of nucleic acids

The simplest molecules grouping the four most common elements of the universe H,C,O and N (with the exception of the biologically inert He) are isocyanate HNCO and formamide H2NCOH. Reasons for the availability of formamide on prebiotic Earth are presented. We review evidence showing that formamide in the presence of largely available catalysts and by moderate heating yields the complete set of nucleic bases necessary for the formation of nucleic acids. Formamide also favours the formation of acyclonucleosides and the phosphorylation and trans-phosphorylation of nucleosides, thus providing a plausible chemical frame for the passage from a simple one-carbon compound to nucleic polymers. Physico-chemical conditions exist in which formamide favours the stability of the phosphoester bonds in nucleic polymers relative to that of the same bonds in monomers. Starting from a formamide-laden environment subject only to the laws of chemistry, a hypothesis is outlined sketching the passage towards an aqueous world in which Darwinian rules apply

GERD in elderly patients: surgical treatment with Nissen-Rossetti laparoscopic technique, outcome.

BACKGROUND: The gastro-esophageal reflux disease (GERD) is one of the most frequent disease of the upper gastro-entheric tract. Surgical treatment is reserved to selected patients, affected by severe forms of disease and/or without compliance to medical therapy. In 95%-60% of the patients submitted to surgical antireflux intervention, a notable improvement of the quality of life is observed. Functional evaluations performed on pre and post – surgical pHmetric and manometric examination have provided new acquisitions about improvements in the restoration of anatomical and functional integrity of the esophagus-gastric antireflux barrier. METHODS: 45 elderly patients with GERD were recruited in a 27 months period. All patients were subjected to laparoscopic Nissen-Rossetti 360° fundoplication. The subjects had a pre-surgical evaluation with: • 24 hours pHmetry, • esophageal manometry, The same evaluation was repeated 1 month and 6 months after surgical intervention. RESULTS: In our series all patients get benefit from surgical treatment, with an improvement of pHmetric and manometric parameters and a regression of complications of GERD such as Barrett's metaplasia. In 8.33% of patients a PPI therapy was necessary, after the surgical intervention, to control symptoms. CONCLUSIONS: The role of surgery in GERD concerns selected patients. Nissen-Rossetti mini-invasive approach is performed with an acceptable percentage of complications (3%-10%). This technique is associated with a good control of GERD symptoms in a short and middle term and with an improvement of functional parameters, such as pHmetric and manometric

L’attività di sorveglianza audiologica pediatrica in Italia: raccomandazioni preliminari

Sulla base dei risultati dei programmi di screening uditivo neonatale attivi in diverse regioni italiane, si è resa necessaria una riflessione riguardo all’identificazione delle ipoacusie sfuggite al programma di screening neonatale, delle ipoacusie progressive o insorte dopo la nascita. Nell’ambito del progetto del Ministero della Salute CCM 2013 “Programma regionale di identificazione, intervento e presa in carico precoci per la prevenzione dei disturbi comunicativi nei bambini con deficit uditivo” un gruppo di esperti ha identificato tre principali raccomandazioni utili per ottimizzare l’attività di sorveglianza audiologica pediatrica nell’ambito del Servizio Sanitari Nazionale. Il pediatra di famiglia è riconosciuto come la figura chiave per il monitoraggio delle capacità uditive e dello sviluppo del bambino

Theratyping of the Rare CFTR Variants E193K and R334W in Rectal Organoid-Derived Epithelial Monolayers

Background: The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare CFTR alleles is often unknown. Several assays have been developed, such as forskolin-induced swelling (FIS), to evaluate the rescue of such uncommon CFTR alleles both by established and novel modulators in patient-derived primary cell cultures (organoids). Presently, we assessed the CFTR-mediated electrical current across rectal organoid-derived epithelial monolayers. This technique, which allows separate measurement of CFTR-dependent chloride or bicarbonate transport, was used to assess the effect of ELX/TEZ/IVA on two rare CFTR variants. Methods: Intestinal organoid cultures were established from rectal biopsies of CF patients carrying the rare missense mutations E193K or R334W paired with F508del. The effect of the CFTR modulator combination ELX/TEZ/IVA on CFTR-mediated Cl- and HCO3- secretion was assessed in organoid-derived intestinal epithelial monolayers. Non-CF organoids were used for comparison. Clinical biomarkers (sweat chloride, FEV1) were monitored in patients receiving modulator therapy. Results: ELX/TEZ/IVA markedly enhanced CFTR-mediated bicarbonate and chloride transport across intestinal epithelium of both patients. Consistent with the rescue of CFTR function in cultured intestinal cells, ELX/TEZ/IVA therapy improved biomarkers of CFTR function in the R334W/F508del patient. Conclusions: Current measurements in organoid-derived intestinal monolayers can readily be used to monitor CFTR-dependent epithelial Cl- and HCO3- transport. This technique can be explored to assess the functional consequences of rare CFTR mutations and the efficacy of CFTR modulators. We propose that this functional CFTR assay may guide personalized medicine in patients with CF-like clinical manifestations as well as in those carrying rare CFTR mutations

A Prototype of a New Generation Readout ASIC in 65 nm CMOS for Pixel Detectors at HL-LHC

The foreseen High-Luminosity upgrade at the CERN Large Hadron Collider (LHC) will constitute a new frontier for particle physics after year 2024, demanding for the installation of new silicon pixel detectors able to withstand unprecedented track densities and radiation levels in the inner tracking systems of current general-purpose experiments. This paper describes the implementation of a new-generation pixel chip demonstrator using a commercial 65 nm CMOS technology and targeting HL-LHC specifications. It was designed as part of the Italian INFN CHIPIX65 project and in close synergy with the international CERN RD53 collaboration on 65 nm CMOS. The prototype is composed of a matrix of 64×64 pixels with 50 μm × 50 μm cells featuring a compact design, low-noise and low-power performance. The pixel array integrates two different analogue front-end architectures working in parallel, one with asynchronous and one with synchronous hit discriminators. Common characteristics are a compact layout able to fit into half the pixel size, low-noise performance (ENC < 100 e− RMS for 50 fF input capacitance), below 5 μW/pixel power consumption, linear charge measurements up to 30 ke− input charge using Time-over-Threshold (ToT) encoding and leakage current compensation up to 50 nA per pixel. A novel region-based digital architecture has been designed in order to ensure > 99% efficiency for expected 3 GHz/cm2 hit rate, 1 MHz trigger rate and 12.5 μs trigger latency at HL-LHC. Pixels have been organized into regions of 4×4 cells and a common synthesized logic shared among all pixels provides a centralized memory for latency buffering, performs the trigger matching and handles the local configuration. The simulated particle inefficiency for this architecture is below 0.1% under nominal HL-LHC conditions. All global biases and voltages required by analogue front-ends are generated on-chip using 10-bit programmable DACs. Bias currents and voltages can be monitored by a 12-bit ADC. A bandgap voltage reference circuit provides a stable reference voltage for all these blocks. The readout of triggered data is based on replicated FIFOs placed at the chip periphery. Data are finally sent off-chip with 8b/10b encoding using a high-speed serializer. Triggerless and debug operating modes are also supported. Chip configuration and slow-control are performed through fully-duplex synchronous Serial Peripheral Interface (SPI) master/slave transactions. The I/O interface uses custom-designed JEDEC-compliant SLVS transmitters and receivers. All blocks and analogue front-ends have been silicon-proven during a previous prototyping phase and were demonstrated to be radiation tolerant up to 580 Mrad Total Ionizing Dose (TID) or beyond. The CHIPIX65 demonstrator was submitted for fabrication on July 2016. It was received back from the foundry on October 2016 and preliminary experimental characterizations started

A Prototype of a New Generation Readout ASIC in 65 nm CMOS for Pixel Detectors at HL-LHC

The foreseen High-Luminosity upgrade at the CERN Large Hadron Collider (LHC) will constitute a new frontier for particle physics after year 2024, demanding for the installation of new silicon pixel detectors able to withstand unprecedented track densities and radiation levels in the inner tracking systems of current general-purpose experiments. This paper describes the implementation of a new-generation pixel chip demonstrator using a commercial 65 nm CMOS technology and targeting HL-LHC specifications. It was designed as part of the Italian INFN CHIPIX65 project and in close synergy with the international CERN RD53 collaboration on 65 nm CMOS. The prototype is composed of a matrix of 64×64 pixels with 50 μm × 50 μm cells featuring a compact design, low-noise and low-power performance. The pixel array integrates two different analogue front-end architectures working in parallel, one with asynchronous and one with synchronous hit discriminators. Common characteristics are a compact layout able to fit into half the pixel size, low-noise performance (ENC < 100 e− RMS for 50 fF input capacitance), below 5 μW/pixel power consumption, linear charge measurements up to 30 ke− input charge using Time-over-Threshold (ToT) encoding and leakage current compensation up to 50 nA per pixel. A novel region-based digital architecture has been designed in order to ensure > 99% efficiency for expected 3 GHz/cm2 hit rate, 1 MHz trigger rate and 12.5 μs trigger latency at HL-LHC. Pixels have been organized into regions of 4×4 cells and a common synthesized logic shared among all pixels provides a centralized memory for latency buffering, performs the trigger matching and handles the local configuration. The simulated particle inefficiency for this architecture is below 0.1% under nominal HL-LHC conditions. All global biases and voltages required by analogue front-ends are generated on-chip using 10-bit programmable DACs. Bias currents and voltages can be monitored by a 12-bit ADC. A bandgap voltage reference circuit provides a stable reference voltage for all these blocks. The readout of triggered data is based on replicated FIFOs placed at the chip periphery. Data are finally sent off-chip with 8b/10b encoding using a high-speed serializer. Triggerless and debug operating modes are also supported. Chip configuration and slow-control are performed through fully-duplex synchronous Serial Peripheral Interface (SPI) master/slave transactions. The I/O interface uses custom-designed JEDEC-compliant SLVS transmitters and receivers. All blocks and analogue front-ends have been silicon-proven during a previous prototyping phase and were demonstrated to be radiation tolerant up to 580 Mrad Total Ionizing Dose (TID) or beyond. The CHIPIX65 demonstrator was submitted for fabrication on July 2016. It was received back from the foundry on October 2016 and preliminary experimental characterizations started

Results from CHIPIX-FE0, a Small-Scale Prototype of a New Generation Pixel Readout ASIC in 65 nm CMOS for HL-LHC

A prototype of a new-generation readout ASIC targeting High-Luminosity (HL) LHC pixel detector upgrades has been designed and fabricated as part of the Italian INFN CHIPIX65 project using a commercial 65 nm CMOS technology. This demonstrator, hereinafter referred to as CHIPIX-FE0, is composed of a matrix of 64 7 64 pixels with 50 \ub5m 7 50 \ub5m pixel size embedding two different architectures of analog front-ends working in parallel. The final layout of the chip was submitted and accepted for fabrication on July 2016. Chips were received back from the foundry on October 2016 and successfully characterized before irradiation. Several irradiation campaigns with X-rays have been accomplished during 2017 at Padova INFN and CERN EP/ESE facilities under different uniformity and temperature conditions up to 630 Mrad Total Ionizing Dose (TID). These studies corfirmed negligible degradation of analog front-ends performance after irradiation. First sample chips have been also bump-bonded to 50 \ub5m 7 50 \ub5m and single readout electrode 25 \ub5m 7 100 \ub5m 3D sensors provided by Trento FBK. This represented a major milestone for the entire CHIPIX65 project, offering to the pixel community the first example of a complete readout chip in 65 nm CMOS technology coupled to such a kind of silicon detectors. Extensive characterizations with laser and radioactive sources have started. This paper briefly summarizes most important pre- and post-irradiation results, along with preliminary results obtained from chips bump-bonded to 3D sensors. Selected components of the CHIPIX65 demonstrator have been finally integrated into the large-scale RD53A prototype submitted at the end of summer 2017 by the CERN RD53 international collaboration on 65 nm CMOS technology

Identifying the unmet information and support needs of women with autoimmune rheumatic diseases during pregnancy planning, pregnancy and early parenting: mixed-methods study

Background Autoimmune rheumatic diseases (ARDs) such as inflammatory arthritis and Lupus, and many of the treatments for these diseases, can have a detrimental impact on fertility and pregnancy outcomes. Disease activity and organ damage as a result of ARDs can affect maternal and foetal outcomes. The safety and acceptability of hormonal contraceptives can also be affected. The objective of this study was to identify the information and support needs of women with ARDs during pregnancy planning, pregnancy and early parenting. Methods This mixed methods study included a cross-sectional online survey and qualitative narrative interviews. The survey was completed by 128 women, aged 18–49 in the United Kingdom with an ARD who were thinking of getting pregnant in the next five years, who were pregnant, or had young children (< 5 years old). The survey assessed quality-of-life and information needs (Arthritis Impact Measurement Scale Short Form and Educational Needs Assessment Tool), support received, what women found challenging, what was helpful, and support women would have liked. From the survey participants, a maximum variation sample of 22 women were purposively recruited for qualitative interviews. Interviews used a person-centered participatory approach facilitated by visual methods, which enabled participants to reflect on their experiences. Interviews were also carried out with seven health professionals purposively sampled from primary care, secondary care, maternity, and health visiting services. Results Survey findings indicated an unmet need for information in this population (ENAT total mean 104.85, SD 30.18). Women at the pre-conception stage reported higher needs for information on pregnancy planning, fertility, giving birth, and breastfeeding, whereas those who had children already expressed a higher need for information on pain and mobility. The need for high quality information, and more holistic, multi-disciplinary, collaborative, and integrated care consistently emerged as themes in the survey open text responses and interviews with women and health professionals. Conclusions There is an urgent need to develop and evaluate interventions to better inform, support and empower women of reproductive age who have ARDs as they navigate the complex challenges that they face during pregnancy planning, pregnancy and early parenting

Design of analog front-ends for the RD53 demonstrator chip

The RD53 collaboration is developing a large scale pixel front-end chip, which will be a tool to evaluate the performance of 65 nm CMOS technology in view of its application to the readout of the innermost detector layers of ATLAS and CMS at the HL-LHC. Experimental results of the characterization of small prototypes will be discussed in the frame of the design work that is currently leading to the development of the large scale demonstrator chip RD53A to be submitted in early 2017. The paper is focused on the analog processors developed in the framework of the RD53 collaboration, including three time over threshold front-ends, designed by INFN Torino and Pavia, University of Bergamo and LBNL and a zero dead time front-end based on flash ADC designed by a joint collaboration between the Fermilab and INFN. The paper will also discuss the radiation tolerance features of the front-end channels, which were exposed to up to 800 Mrad of total ionizing dose to reproduce the system operation in the actual experiment

RD53 Collaboration and CHIPIX65 Project for the development of an innovative Pixel Front End Chip for HL-LHC

Pixel detectors at HL-LHC experiments will be exposed to unprecedented level of radiation and particle flux. This paper describes the program of development of an innovative pixel chip using a CMOS 65nm technology for the first time in HEP community, for experiments with extreme particle rates and radiation at future High Energy Physics colliders. The RD53 collaboration effort is described together with the CHIPIX65 INFN project