Determinazione della carica di CMV in campioni di sangue essiccato su carta da filtro (DBS)

Introduzione. Un\u2019elevata carica virale in urine o sangue di neonati con infezione congenita da Cytomegalovirus (CMV) potrebbe rappresentare un marcatore di prognosi sfavorevole. Diversi studi hanno evidenziato i numerosi vantaggi legati all\u2019impiego del sangue essiccato su Guthrie card (DBS). Pertanto sarebbe molto utile determinare la carica di CMV-DNA in questo tipo di campione, raccolto routinariamente alla nascita. L\u2019obiettivo di questo lavoro preliminare \ue8 stato verificare la correlazione tra le cariche rilevate nel sangue fresco (SF) e nei corrispondenti DBS. Metodi. Sono stati esaminati 69 campioni di SF e DBS, appartenenti a soggetti con infezione da CMV, risultati positivi per CMV-DNA in nested-PCR. Il DNA virale \ue8 stato estratto con colonne di affinit\ue0 (QIAGEN) e quantificato mediante Real-time PCR commerciale (Nanogen). Risultati. La PCR quantitativa ha dato esito positivo in 64 campioni di SF ed in soli 25 DBS. La carica nei DBS (mediana: 1,09x103 copie/ml) \ue8 risultata significativamente inferiore (p<0,05) a quella del SF corrispondente (1,67x104 copie/ml). Anche le mediane delle cariche virali del SF dal quale sono stati ottenuti i 39 DBS negativi ed i 25 positivi (1,10x103 vs 1,67x104 copie/ml) sono risultate significativamente diverse. Conclusioni. I risultati ottenuti non solo hanno evidenziato una riduzione della quantit\ue0 di CMV-DNA tra SF e corrispondente DBS pari a circa 1 log, presumibilmente dovuta alla minore quantit\ue0 di sangue esaminato, ma anche una minore sensibilit\ue0 del sistema. Essendo l\u2019alta carica virale indice di insorgenza di sequele nei neonati congenitamente infetti, riteniamo che il metodo proposto consenta comunque di individuare i soggetti da monitorare in quanto maggiormente a rischio di complicanze tardive. Il nostro gruppo sta gi\ue0 applicando tale metodica a DBS di neonati con infezione congenita dei quali \ue8 possibile reperire le informazioni relative alla sintomatologia alla nascita ed al follow-up

A new limit on the light speed isotropy from the GRAAL experiment at the ESRF

When the electrons stored in the ring of the European Synchrotron Radiation Facility (ESRF, Grenoble) scatter on a laser beam (Compton scattering in flight) the lower energy of the scattered electron spectra, the Compton Edge (CE), is given by the two body photon-electron relativistic kinematics and depends on the velocity of light. A precision measurement of the position of this CE as a function of the daily variations of the direction of the electron beam in an absolute reference frame provides a one-way test of Relativistic Kinematics and the isotropy of the velocity of light. The results of GRAAL-ESRF measurements improve the previously existing one-way limits, thus showing the efficiency of this method and the interest of further studies in this direction.Comment: Proceed. MG12 meeting, Paris, July, 200

Limits on light-speed anisotropies from Compton scattering of high-energy electrons

The possibility of anisotropies in the speed of light relative to the limiting speed of electrons is considered. The absence of sidereal variations in the energy of Compton-edge photons at the ESRF's GRAAL facility constrains such anisotropies representing the first non-threshold collision-kinematics study of Lorentz violation. When interpreted within the minimal Standard-Model Extension, this result yields the two-sided limit of 1.6 x 10^{-14} at 95% confidence level on a combination of the parity-violating photon and electron coefficients kappa_{o+} and c. This new constraint provides an improvement over previous bounds by one order of magnitude.Comment: 4 pages, 4 figure

Measurement of eta photoproduction on the proton from threshold to 1500 MeV

Beam asymmetry and differential cross section for the reaction gamma+p->eta+p were measured from production threshold to 1500 MeV photon laboratory energy. The two dominant neutral decay modes of the eta meson, eta->2g and eta->3pi0, were analyzed. The full set of measurements is in good agreement with previously published results. Our data were compared with three models. They all fit satisfactorily the results but their respective resonance contributions are quite different. The possible photoexcitation of a narrow state N(1670) was investigated and no evidence was found.Comment: 18 pages, 14 figures, 4 tables Submitted to EPJ

A tailored psychological intervention for anxiety and depression management in people with chronic obstructive pulmonary disease: TANDEM RCT and process evaluation

Background: People with chronic obstructive pulmonary disease have high levels of anxiety and depression, which is associated with increased morbidity and poor uptake of effective treatments, such as pulmonary rehabilitation. Cognitive-behavioural therapy improves mental health of people with long-term conditions and could potentially increase uptake of pulmonary rehabilitation, enabling synergies that could enhance the mental health of people with chronic obstructive pulmonary disease. Aim: Our aim was to develop and evaluate the clinical effectiveness and cost effectiveness of a tailored cognitive-behavioural approach intervention, which links into, and optimises the benefits of, routine pulmonary rehabilitation. Design: We carried out a pragmatic multicentre randomised controlled trial using a 1.25 : 1 ratio (intervention : control) with a parallel process evaluation, including assessment of fidelity. Setting: Twelve NHS trusts and five Clinical Commissioning Groups in England were recruited into the study. The intervention was delivered in participant\u27s own home or at a local NHS facility, and by telephone. Participants: Between July 2017 and March 2020 we recruited adults with moderate/very severe chronic obstructive pulmonary disease and mild/moderate anxiety and/or depression, meeting eligibility criteria for assessment for pulmonary rehabilitation. Carers of participants were invited to participate. Intervention: The cognitive-behavioural approach intervention (i.e. six to eight 40- to 60-minute sessions plus telephone support throughout pulmonary rehabilitation) was delivered by 31 trained respiratory healthcare professionals to participants prior to commencing pulmonary rehabilitation. Usual care included routine pulmonary rehabilitation referral. Main outcome measures: Co-primary outcomes were Hospital Anxiety and Depression Scale - anxiety and Hospital Anxiety and Depression Scale - depression at 6 months post randomisation. Secondary outcomes at 6 and 12 months included health-related quality of life, smoking status, uptake of pulmonary rehabilitation and healthcare use. Results: We analysed results from 423 randomised participants (intervention, n = 242; control, n = 181). Forty-three carers participated. Follow-up at 6 and 12 months was 93% and 82%, respectively. Despite good fidelity for intervention delivery, mean between-group differences in Hospital Anxiety and Depression Scale at 6 months ruled out clinically important effects (Hospital Anxiety and Depression Scale - anxiety mean difference -0.60, 95% confidence interval -1.40 to 0.21; Hospital Anxiety and Depression Scale - depression mean difference -0.66, 95% confidence interval -1.39 to 0.07), with similar results at 12 months. There were no between-group differences in any of the secondary outcomes. Sensitivity analyses did not alter these conclusions. More adverse events were reported for intervention participants than for control participants, but none related to the trial. The intervention did not generate quality-of-life improvements to justify the additional cost (adjusted mean difference \ua3770.24, 95% confidence interval -\ua327.91 to \ua31568.39) to the NHS. The intervention was well received and many participants described positive affects on their quality of life. Facilitators highlighted the complexity of participants\u27 lives and considered the intervention to be of potential valuable; however, the intervention would be difficult to integrate within routine clinical services. Our well-powered trial delivered a theoretically designed intervention with good fidelity. The respiratory-experienced facilitators were trained to deliver a low-intensity cognitive-behavioural approach intervention, but high-intensity cognitive-behavioural therapy might have been more effective. Our broad inclusion criteria specified objectively assessed anxiety and/or depression, but participants were likely to favour talking therapies. Randomisation was concealed and blinding of outcome assessment was breached in only 15 participants. Conclusions: The tailored cognitive-behavioural approach intervention delivered with fidelity by trained respiratory healthcare professionals to people with chronic obstructive pulmonary disease was neither clinically effective nor cost-effective. Alternative approaches that are integrated with routine long-term condition care are needed to address the unmet, complex clinical and psychosocial needs of this group of patients. Trial registration: This trial is registered as ISRCTN59537391. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/146/02) and is published in full in Health Technology Assessment; Vol. 28, No. 1. See the NIHR Funding and Awards website for further award information.People with long-standing lung problems, such as chronic obstructive pulmonary disease, often also have anxiety and depression, which further reduces their quality of life. Two existing treatments could help. Pulmonary rehabilitation (a programme of exercise and education) improves both the physical and mental health of people with chronic obstructive pulmonary disease. Cognitive–behavioural therapy (a talking therapy) may reduce anxiety and depression. The TANDEM [Tailored intervention for Anxiety and Depression Management in chronic obstructive pulmonary disease (COPD)] intervention linked these two treatments by providing talking therapy based on cognitive–behavioural therapy during the waiting time following referral for pulmonary rehabilitation. The TANDEM treatment was delivered by respiratory healthcare professionals (e.g. nurses or physiotherapists) trained to deliver the talking therapy in six to eight weekly sessions. The sessions were conducted in the participant’s home (or another convenient location), with brief telephone support during the pulmonary rehabilitation. Of 423 participants recruited to the study, 242 participants received TANDEM talking therapy and 181 participants received usual care (including a referral to pulmonary rehabilitation). We measured mental health, quality of life, social life, attendance at pulmonary rehabilitation and healthcare use in both groups at 6 and 12 months. Forty-three carers joined the study and we assessed their mental well-being. We interviewed patients, carers and health professionals to find out their views and experience of the TANDEM treatment. We also examined whether or not the TANDEM treatment was good value for money. The TANDEM treatment did not improve the mental or the physical health of people with chronic obstructive pulmonary disease. In addition, the TANDEM treatment cost the NHS an extra \ua3770 per patient, which was not good value for money. The TANDEM treatment was well received, and many participants told us how it had helped them. Heath-care professionals noted how participants did not just have chronic obstructive pulmonary disease, but were coping with many physical, mental and social problems. The TANDEM intervention was not effective and, therefore, other strategies will be needed to help people with chronic obstructive pulmonary disease and mental health problems live with their condition

Measurement of the Neutron Radius of 208Pb Through Parity-Violation in Electron Scattering

We report the first measurement of the parity-violating asymmetry A_PV in the elastic scattering of polarized electrons from 208Pb. A_PV is sensitive to the radius of the neutron distribution (Rn). The result A_PV = 0.656 \pm 0.060 (stat) \pm 0.014 (syst) ppm corresponds to a difference between the radii of the neutron and proton distributions Rn - Rp = 0.33 +0.16 -0.18 fm and provides the first electroweak observation of the neutron skin which is expected in a heavy, neutron-rich nucleus.Comment: 6 pages, 1 figur

Dark matter search in a Beam-Dump eXperiment (BDX) at Jefferson Lab

MeV-GeV dark matter (DM) is theoretically well motivated but remarkably unexplored. This Letter of Intent presents the MeV-GeV DM discovery potential for a 1 m$^3$ segmented plastic scintillator detector placed downstream of the beam-dump at one of the high intensity JLab experimental Halls, receiving up to 10$^{22}$ electrons-on-target (EOT) in a one-year period. This experiment (Beam-Dump eXperiment or BDX) is sensitive to DM-nucleon elastic scattering at the level of a thousand counts per year, with very low threshold recoil energies ($\sim$1 MeV), and limited only by reducible cosmogenic backgrounds. Sensitivity to DM-electron elastic scattering and/or inelastic DM would be below 10 counts per year after requiring all electromagnetic showers in the detector to exceed a few-hundred MeV, which dramatically reduces or altogether eliminates all backgrounds. Detailed Monte Carlo simulations are in progress to finalize the detector design and experimental set up. An existing 0.036 m$^3$ prototype based on the same technology will be used to validate simulations with background rate estimates, driving the necessary R$\&$D towards an optimized detector. The final detector design and experimental set up will be presented in a full proposal to be submitted to the next JLab PAC. A fully realized experiment would be sensitive to large regions of DM parameter space, exceeding the discovery potential of existing and planned experiments by two orders of magnitude in the MeV-GeV DM mass range.Comment: 28 pages, 17 figures, submitted to JLab PAC 4

A Proposal for a Three Detector Short-Baseline Neutrino Oscillation Program in the Fermilab Booster Neutrino Beam

A Short-Baseline Neutrino (SBN) physics program of three LAr-TPC detectors located along the Booster Neutrino Beam (BNB) at Fermilab is presented. This new SBN Program will deliver a rich and compelling physics opportunity, including the ability to resolve a class of experimental anomalies in neutrino physics and to perform the most sensitive search to date for sterile neutrinos at the eV mass-scale through both appearance and disappearance oscillation channels. Using data sets of 6.6e20 protons on target (P.O.T.) in the LAr1-ND and ICARUS T600 detectors plus 13.2e20 P.O.T. in the MicroBooNE detector, we estimate that a search for muon neutrino to electron neutrino appearance can be performed with ~5 sigma sensitivity for the LSND allowed (99% C.L.) parameter region. In this proposal for the SBN Program, we describe the physics analysis, the conceptual design of the LAr1-ND detector, the design and refurbishment of the T600 detector, the necessary infrastructure required to execute the program, and a possible reconfiguration of the BNB target and horn system to improve its performance for oscillation searches.Comment: 209 pages, 129 figure

First Measurement of the Σ\Sigma Beam Asymmetry in η′\eta^{\prime} Photoproduction off the Proton near Threshold

The $\Sigma$ beam asymmetry in $\eta^{\prime}$ photoproduction off the proton was measured at the GrAAL polarised photon beam with incoming photon energies of 1.461 and 1.480 GeV. For both energies the asymmetry as a function of the meson production angle shows a clear structure, more pronounced at the lowest one, with a change of sign around 90$^o$. The observed behaviour is compatible with P-wave D-wave (or S-wave F-wave) interference, the closer to threshold the stronger. The results are compared to the existing state-of-the-art calculations that fail to account for the data.Comment: 6 pages, 4 figures, accepted for publication on Eur. Phys. J

Allelic HLA Matching and Pair Origin Are Favorable Prognostic Factors for Unrelated Hematopoietic Stem Cell Transplantation in Neoplastic Hematologic Diseases: An Italian Analysis by the Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti

HLA molecules are important for immunoreactivity in allogeneic hematopoietic stem cell transplantation (HSCT). The Gruppo Italiano Trapianto di Cellule Staminali e Terapie Cellulari, Italian Bone Marrow Donor Registry, and Associazione Italiana di Immunogenetica e Biologia dei Trapianti promoted a retrospective observational study to evaluate HLA matching and the impact of allelic HLA mismatching and non-HLA factors on unrelated Italian HSCT outcomes. From 2012 to 2015, 1788 patients were enrolled in the study. The average donor age was 29 years and the average recipient age was 49 years. As a conditioning regimen, 71% of the patients received myeloablative conditioning. For GVHD prophylaxis, 76% received either antithymocyte or anti-T lymphocyte globulin, cyclosporine A, and methotrexate. Peripheral blood was the stem cell source in 80%. The median duration of follow-up was 53 months. Regarding HLA matching, 50% of donor-recipient pairs were 10/10 matched, 38% had 1 mismatch, and 12% had 2 or more mismatches. A total of 302 pairs shared Italian origin. Four-year overall survival (OS), progression-free survival, GVHD-free relapse-free survival, and relapse rates were 49%, 40%, 22%, and 34%, respectively. The 4-year NRM was 27%, and the 100-day cumulative incidence of grade 65II acute GVHD (aGVHD) was 26%. In multivariate analysis, 9/10 and 648/10 HLA allele-matched pairs were associated with worse OS (P = .04 and .007, respectively), NRM (P = .007 and P < .0001, respectively), and grade III-IV aGVHD (P = .0001 and .01, respectively). Moreover, the incidences of grade II-IV aGVHD (P = .001) and chronic GVHD (P = .002) were significantly lower in Italian pairs. In conclusion, 10/10 HLA matching is a favorable prognostic factor for unrelated HSCT outcome in the Italian population. Moreover, the presence of 2 HLA-mismatched loci was associated with a higher NRM (P < .0001) and grade II-IV aGVHD (P = .006) and a poorer OS (P = .001) compared with 1 HLA-mismatched locus in early or intermediate disease phases. Finally, we found that Italian donor and recipient origin is a favorable prognostic factor for GVHD occurrence