Hydroxypyridinones with enhanced iron chelating properties. Synthesis, characterization and in vivo tests of 5-hydroxy-2-(hydroxymethyl)pyridine-4(1H)-one

The synthesis of 5-hydroxy-2-(hydroxymethyl)pyridin-4(1H)-one (P1) is presented, together with the evaluation of its coordination ability towards Fe3+, studied by a combination of chemical, computational, and animal approaches. The use of complementary analytical techniques has allowed us to give evidence of the tautomeric changes of P1 as a function of pH, and to determine their influence on the coordinating ability of P1 towards Fe3+. The pFe3+ value 22.0 of P1–iron complexes is noticeably higher than that of deferiprone (20.6), one of the three clinical chelating agents in therapeutic use for iron overload diseases. This is due on one side to the tautomeric change to the catechol form, and on the other to the lower protonation constant of the OH group. Bio-distribution studies on mice allowed us to confirm in vivo the efficacy of P1. Furthermore the coordinating ability toward Al3+, Cu2+ and Zn2+ has been studied to evalu- ate the possible use of P1 against a second toxic metal ion (Al3+), and to envisage its potential influence on the homeostatic equilibria of essential metal ions. The chelating ability of P1 toward these ions, not higher than that of the corresponding deferiprone, contributes to render P1 a more selective iron chelato

The QUIJOTE TGI

The QUIJOTE TGI instrument is currently being assembled and tested at the IAC in Spain. The TGI is a 31 pixel 26-36 GHz polarimeter array designed to be mounted at the focus of the second QUIJOTE telescope. This follows a first telescope and multi-frequency instrument that have now been observing almost 2 years. The polarimeter design is based on the QUIET polarimeter scheme but with the addition of an extra 90º phase switch which allows for quasiinstantaneous complete QUI measurements through each detector. The advantage of this is a reduction in the systematics associated with differencing two independent radiometer channels. The polarimeters are split into a cold front end and a warm back end. The back end is a highly integrated design by engineers at DICOM. It is also sufficiently modular for testing purposes. In this presentation the high quality wide band components used in the optical design (also designed in DICOM) are presented as well as the novel cryogenic modular design. Each polarimeter chain is accessible individually and can be removed from the cryostat and replaced without having to move the remaining pixels. The optical components work over the complete Ka band showing excellent performance. Results from the sub unit measurements are presented and also a description of the novel calibration technique that allows for bandpass measurement and polar alignment. Terrestrial Calibration for this instrument is very important and will be carried out at three points in the commissioning phase: in the laboratory, at the telescope site and finally a reduce set of calibrations will be carried out on the telescope before measurements of extraterrestrial sources begin. The telescope pointing model is known to be more precise than the expected calibration precision so no further significant error will be added through the telescope optics. The integrated back-end components are presented showing the overall arrangement for mounting on the cryostat. Many of the microwave circuits are in-house designs with performances that go beyond commercially available products. Individual component performance is be presented showing for each of the sub modules

The QUIJOTE experiment: project status and first scientific results

We present the current status of the QUIJOTE (Q-U-I JOint TEnerife) experiment, a new polarimeter with the aim of characterizing the polarization of the Cosmic Microwave Background, and other galactic or extra-galactic physical processes that emit in microwaves in the frequency range 10–42 GHz, and at large angular scales (around 1 degree resolution). The experiment has been designed to reach the required sensitivity to detect a primordial gravitational wave component in the CMB, provided its tensor-to-scalar ratio is larger than r ∼ 0.05. The project consists of two telescopes and three instruments which will survey a large sky area from the Teide Observatory to provide I, Q and U maps of high sensitivity. The first QUIJOTE instrument, known as Multi-Frequency Instrument (MFI), has been surveying the northern sky in four individual frequencies between 10 and 20 GHz since November 2012, providing data with an average sensitivity of 80 µK beam−1 in Q and U in a region of 20, 000 square-degrees. The second instrument, or Thirty-GHz Instrument (TGI), is currently undergoing the commissioning phase, and the third instrument, or Forty-GHz Instrument (FGI), is in the final fabrication phase. Finally, we describe the first scientific results obtained with the MFI. Some specific regions, mainly along the Galactic plane, have been surveyed to a deeper depth, reaching sensitivities of around 40 µK beam−1. We present new upper limits on the polarization of the anomalous dust emission, resulting from these data, in the Perseus molecular complex and in the W43 molecular complex

The QUIJOTE-CMB experiment: studying the polarisation of the galactic and cosmological microwave emissions

The QUIJOTE (Q-U-I JOint Tenerife) CMB Experiment will operate at the Teide Observatory with the aim of characterizing the polarisation of the CMB and other processes of Galactic and extragalactic emission in the frequency range of 10-40GHz and at large and medium angular scales. The first of the two QUIJOTE telescopes and the first multi-frequency (10-30GHz) instrument are already built and have been tested in the laboratory. QUIJOTE-CMB will be a valuable complement at low frequencies for the Planck mission, and will have the required sensitivity to detect a primordial gravitational-wave component if the tensor-to-scalar ratio is larger than r = 0.05.The QUIJOTE-CMB experiment is being developed by the Instituto de Astrofisica de Canarias (IAC), the Instituto de Fisica de Cantabria (IFCA), and the Universities of Cantabria, Manchester and Cambridge. Partial financial support is provided by the Spanish Ministry of Economy and Competitiveness (MINECO) under the projects AYA2010-21766-C03 (01, 02 and 03), and also by the Consolider-Ingenio project CSD2010-00064 (EPI: Exploring the Physics of Inflation49)

Mortality and pulmonary complications in patients undergoing surgery with perioperative sars-cov-2 infection: An international cohort study

Background The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). Interpretation Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks