INRISCO: INcident monitoRing in Smart COmmunities

Major advances in information and communication technologies (ICTs) make citizens to be considered as sensors in motion. Carrying their mobile devices, moving in their connected vehicles or actively participating in social networks, citizens provide a wealth of information that, after properly processing, can support numerous applications for the benefit of the community. In the context of smart communities, the INRISCO [1] proposal intends for (i) the early detection of abnormal situations in cities (i.e., incidents), (ii) the analysis of whether, according to their impact, those incidents are really adverse for the community; and (iii) the automatic actuation by dissemination of appropriate information to citizens and authorities. Thus, INRISCO will identify and report on incidents in traffic (jam, accident) or public infrastructure (e.g., works, street cut), the occurrence of specific events that affect other citizens' life (e.g., demonstrations, concerts), or environmental problems (e.g., pollution, bad weather). It is of particular interest to this proposal the identification of incidents with a social and economic impact, which affects the quality of life of citizens.This work was supported in part by the Spanish Government through the projects INRISCO under Grant TEC2014-54335-C4-1-R, Grant TEC2014-54335-C4-2-R, Grant TEC2014-54335-C4-3-R, and Grant TEC2014-54335-C4-4-R, in part by the MAGOS under Grant TEC2017-84197-C4-1-R, Grant TEC2017-84197-C4-2-R, and Grant TEC2017-84197-C4-3-R, in part by the European Regional Development Fund (ERDF), and in part by the Galician Regional Government under agreement for funding the Atlantic Research Center for Information and Communication Technologies (AtlantTIC)

Recessive mutations in the INS gene result in neonatal diabetes through reduced insulin biosynthesis

Heterozygous coding mutations in the INS gene that encodes preproinsulin were recently shown to be an important cause of permanent neonatal diabetes. These dominantly acting mutations prevent normal folding of proinsulin, which leads to beta-cell death through endoplasmic reticulum stress and apoptosis. We now report 10 different recessive INS mutations in 15 probands with neonatal diabetes. Functional studies showed that recessive mutations resulted in diabetes because of decreased insulin biosynthesis through distinct mechanisms, including gene deletion, lack of the translation initiation signal, and altered mRNA stability because of the disruption of a polyadenylation signal. A subset of recessive mutations caused abnormal INS transcription, including the deletion of the C1 and E1 cis regulatory elements, or three different single base-pair substitutions in a CC dinucleotide sequence located between E1 and A1 elements. In keeping with an earlier and more severe beta-cell defect, patients with recessive INS mutations had a lower birth weight (-3.2 SD score vs. -2.0 SD score) and were diagnosed earlier (median 1 week vs. 10 weeks) compared to those with dominant INS mutations. Mutations in the insulin gene can therefore result in neonatal diabetes as a result of two contrasting pathogenic mechanisms. Moreover, the recessively inherited mutations provide a genetic demonstration of the essential role of multiple sequence elements that regulate the biosynthesis of insulin in man

Study protocol for a pragmatic randomised controlled trial in general practice investigating the effectiveness of acupuncture against migraine

<p>Abstract</p> <p>Background</p> <p>Migraine is a chronic neurologic disease that can severely affect the patient's quality of life. Although in recent years many randomised studies have been carried out to investigate the effectiveness of acupuncture as a treatment for migraine, it remains a controversial issue. Our aim is to determine whether acupuncture, applied under real conditions of clinical practice in the area of primary healthcare, is more effective than conventional treatment.</p> <p>Methods/Design</p> <p>The design consists of a pragmatic multi-centre, three-armed randomised controlled trial, complemented with an economic evaluation of the results achieved, comparing the effectiveness of verum acupuncture with sham acupuncture, and with a control group receiving normal care only.</p> <p>Patients eligible for inclusion will be those presenting in general practice with migraine and for whom their General Practitioner (GP) is considering referral for acupuncture. Sampling will be by consecutive selection, and by randomised allocation to the three branches of the study, in a centralised way following a 1:1:1 distribution (verum acupuncture; sham acupuncture; conventional treatment). Secondly, one patient in three will be randomly selected from each of the acupuncture (verum or sham) groups for a brain perfusion study (by single photon emission tomography). The treatment with verum acupuncture will consist of 8 treatment sessions, once a week, at points selected individually by the acupuncturist. The sham acupuncture group will receive 8 sessions, one per week, with treatment being applied at non-acupuncture points in the dorsal and lumbar regions, using the minimal puncture technique. The control group will be given conventional treatment, as will the other two groups.</p> <p>Discussion</p> <p>This trial will contribute to available evidence on acupuncture for the treatment of migraine. The primary endpoint is the difference in the number of days with migraine among the three groups, between the baseline period (the 4 weeks prior to the start of treatment) and the period from weeks 9 to 12. As a secondary aspect, we shall record the index of laterality and the percentage of change in the mean count per pixel in each region of interest measured by the brain perfusion tomography, performed on a subsample of the patients within the real and sham acupuncture groups.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN98703707.</p

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Measurement of lepton universality parameters in B+→K+ℓ+ℓ−B^+\to K^+\ell^+\ell^- and B0→K∗0ℓ+ℓ−B^0\to K^{*0}\ell^+\ell^- decays

A simultaneous analysis of the $B^+\to K^+\ell^+\ell^-$ and $B^0\to K^{*0}\ell^+\ell^-$ decays is performed to test muon-electron universality in two ranges of the square of the dilepton invariant mass, $q^2$. The measurement uses a sample of beauty meson decays produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of $9$ $\text{fb}^{-1}$. A sequence of multivariate selections and strict particle identification requirements produce a higher signal purity and a better statistical sensitivity per unit luminosity than previous LHCb lepton universality tests using the same decay modes. Residual backgrounds due to misidentified hadronic decays are studied using data and included in the fit model. Each of the four lepton universality measurements reported is either the first in the given $q^2$ interval or supersedes previous LHCb measurements. The results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-045.html (LHCb public pages

Fraction of χc\chi_c decays in prompt J/ψJ/\psi production measured in pPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

The fraction of $\chi_{c1}$ and $\chi_{c2}$ decays in the prompt $J/\psi$ yield, $F_{\chi c}=\sigma_{\chi_c \to J/\psi}/\sigma_{J/\psi}$, is measured by the LHCb detector in pPb collisions at $\sqrt{s_{NN}}=8.16$ TeV. The study covers the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions, where $y^*$ is the $J/\psi$ rapidity in the nucleon-nucleon center-of-mass system. Forward and backward rapidity samples correspond to integrated luminosities of 13.6 $\pm$ 0.3 nb$^{-1}$ and 20.8 $\pm$ 0.5 nb$^{-1}$, respectively. The result is presented as a function of the $J/\psi$ transverse momentum $p_{T,J/\psi}$ in the range 1$<p_{T, J/\psi}<20$ GeV/$c$. The $F_{\chi c}$ fraction at forward rapidity is compatible with the LHCb measurement performed in $pp$ collisions at $\sqrt{s}=7$ TeV, whereas the result at backward rapidity is 2.4 $\sigma$ larger than in the forward region for $1<p_{T, J/\psi}<3$ GeV/$c$. The increase of $F_{\chi c}$ at low $p_{T, J/\psi}$ at backward rapidity is compatible with the suppression of the $\psi$(2S) contribution to the prompt $J/\psi$ yield. The lack of in-medium dissociation of $\chi_c$ states observed in this study sets an upper limit of 180 MeV on the free energy available in these pPb collisions to dissociate or inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb public pages

Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the Ωc0\Omega_{c}^{0} baryon

The first observation of the singly Cabibbo-suppressed $\Omega_{c}^{0}\to\Omega^{-}K^{+}$ and $\Omega_{c}^{0}\to\Xi^{-}\pi^{+}$ decays is reported, using proton-proton collision data at a centre-of-mass energy of $13\,{\rm TeV}$, corresponding to an integrated luminosity of $5.4\,{\rm fb}^{-1}$, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}K^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.0608\pm0.0051({\rm stat})\pm 0.0040({\rm syst})$, $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Xi^{-}\pi^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.1581\pm0.0087({\rm stat})\pm0.0043({\rm syst})\pm0.0016({\rm ext})$. In addition, using the $\Omega_{c}^{0}\to\Omega^{-}\pi^{+}$ decay channel, the $\Omega_{c}^{0}$ baryon mass is measured to be $M(\Omega_{c}^{0})=2695.28\pm0.07({\rm stat})\pm0.27({\rm syst})\pm0.30({\rm ext})\,{\rm MeV}/c^{2}$, improving the precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.html (LHCb public pages

First observation and branching fraction measurement of the Λb0→Ds−p\Lambda_b^0\to D_s^- p decay

The first observation of the $\Lambda_b^0\to D_s^- p$ decay is presented using proton-proton collision data collected by the LHCb experiment at a centre-of-mass energy of ${\sqrt{s}=13 \,\textrm{TeV}}$, corresponding to a total integrated luminosity of $6\,\textrm{fb}^{-1}$. Using the $\Lambda_b^0\to\Lambda_c^+\pi^-$ decay as the normalisation mode, the branching fraction of the $\Lambda_b^0\to D_s^- p$ decay is measured to be ${\mathcal{B}(\Lambda_b^0\to D_s^- p)=(12.6 \pm 0.5 \pm 0.3 \pm 1.2 )\times 10^{-6}}$, where the first uncertainty is statistical, the second systematic and the third due to uncertainties in the branching fractions of the $\Lambda_b^0\to\Lambda_c^+\pi^-$, $D_s^- \to K^-K^+\pi^-$ and $\Lambda_c^+\to p K^- \pi^+$ decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-038.html (LHCb public pages

Measurement of ZZ boson production cross-section in pppp collisions at s=5.02\sqrt{s} = 5.02 TeV

The first measurement of the $Z$ boson production cross-section at centre-of-mass energy $\sqrt{s} = 5.02\,$TeV in the forward region is reported, using $pp$ collision data collected by the LHCb experiment in year 2017, corresponding to an integrated luminosity of $100 \pm 2\,\rm{pb^{-1}}$. The production cross-section is measured for final-state muons in the pseudorapidity range $2.0 20\,\rm{GeV/}\it{c}$. The integrated cross-section is determined to be $$\sigma_{Z \rightarrow \mu^{+}\mu^{-}} = 39.6 \pm 0.7\,(\rm{stat}) \pm 0.6\,(\rm{syst}) \pm 0.8\,(\rm{lumi}) \ \rm{pb}$$ for the di-muon invariant mass in the range $60<M_{\mu\mu}<120\,\rm{GeV/}\it{c^{2}}$. This result and the differential cross-section results are in good agreement with theoretical predictions at next-to-next-to-leading order in the strong coupling. Based on a previous LHCb measurement of the $Z$ boson production cross-section in $p$Pb collisions at $\sqrt{s_{NN}}=5.02$ TeV, the nuclear modification factor $R_{p\rm{Pb}}$ is measured for the first time at this energy. The measured values are $1.2^{+0.5}_{-0.3}\,(\rm{stat}) \pm 0.1\,(\rm{syst})$ in the forward region ($1.53<y^*_{\mu}<4.03$) and $3.6^{+1.6}_{-0.9}\,(\rm{stat}) \pm 0.2\,(\rm{syst})$ in the backward region ($-4.97<y^*_{\mu}<-2.47$), where $y^*_{\mu}$ represents the muon rapidity in the centre-of-mass frame.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-010.html (LHCb public pages