Calling for an exponential escalation scheme in vaccine development for COVID-19

Purpose!#!COVID-19 as a pandemic calls for rapid development of vaccines.!##!Methods!#!Here a proposal of a seamless, adaptive, phase 1-3 trial for accelerated vaccine development is described.!##!Results!#!Starting at 10, the number of vaccinated volunteers would exponentially increase by tenfold at an interval of 2 weeks; close surveillance of antibody responses, safety and efficacy is necessary. After only 16 weeks, general vaccination would be feasible if supply meets the demand.!##!Conclusion!#!A COVID-19 vaccine would be rapidly available at a slightly increased risk for undetected late side effects or insufficient efficacy if compared with standard vaccine development schemes

Head to head comparisons in performance of CD4 point-of-care assays: a Bayesian meta-analysis (2000–2013)

Abstract Timely detection, staging, and treatment initiation are pertinent to controlling HIV infection. CD4+ cell-based point-of-care (POC) devices offer the potential to rapidly stage patients, and decide on initiating treatment, but a comparative evaluation of their performance has not yet been performed. With this in mind, we conducted a systematic review and meta-analyses. For the period January 2000 to April 2014, 19 databases were systematically searched, 6619 citations retrieved, and 25 articles selected. Diagnostic performance was compared across devices (i.e., PIMA, CyFlow, miniPOC, MBioCD4 System) and across specimens (i.e., capillary blood vs. venous blood). A Bayesian approach was used to meta-analyze the data. The primary outcome, the Bland–Altman (BA) mean bias (which represents agreement between cell counts from POC device and flow cytometry), was analyzed with a Bayesian hierarchical normal model. We performed a head-to-head comparison of two POC devices including the PIMA and PointCareNOW CD4. PIMA appears to perform better vs. PointCareNOW with venous samples (BA mean bias: –9.5 cells/μL; 95% CrI: –37.71 to 18.27, vs. 139.3 cells/μL; 95% CrI: –0.85 to 267.4, mean difference = 148.8, 95% CrI: 11.8, 285.8); importantly, PIMA performed well when used with capillary samples (BA mean bias: 2.2 cells/μL; 95% CrI: –19.32 to 23.6). Sufficient data were available to allow pooling of sensitivity and specificity data only at the 350 cells/μL cutoff. For PIMA device sensitivity 91.6 (84.7–95.5) and specificity was 94.8 (90.1–97.3), respectively. There were not sufficient data to allow comparisons between any other devices. PIMA device was comparable to flow cytometry. The estimated differences between the CD4+ cell counts of the device and the reference was small and best estimated in capillary blood specimens. As the evidence stands, the PointCareNOW device will need to improve prior to widespread use and more data on MBio and MiniPOC are needed. Findings inform implementation of PIMA and improvements in other CD4 POC device prior to recommending widespread use

The social worker in community mental health teams:Findings from a national survey

Summary Social workers have been members of community mental health teams (CMHTs) for many years. However, a combination of factors has resulted in their removal from CMHTs in some areas in recent years. This study presents findings from a 2018 national survey of CMHT team managers (44% response rate), to ascertain the current position of the social worker within CMHTs in England. Analyses focussed on membership, roles and tasks, and change within the previous 12 months. Descriptive statistics were used to analyse the quantitative data and content analysis to interpret free text comments. Findings Social workers were found to undertake a variety of generic roles and tasks but were reported to do so proportionally less often than nurses. A large minority were involved in non-traditional social work tasks such as monitoring medication. In one-fifth of teams, managers thought they had too few social workers. Free text comments suggested that managers valued social workers for their social perspective and expressed concern regarding their removal or the curtailment of their role, perceiving this as having a negative effect on overall CMHT service delivery. Applications The findings provide evidence of some instability in the position of social workers within CMHTs in relation to both their membership and their involvement in traditional and non-traditional roles and tasks. Free text comments suggest that if a biopsychosocial model of mental health support, now recognised as essential to long-term wellbeing, is to be achieved, a social work presence in CMHTs is required

Potential of ultra-high-resolution photon-counting CT of bone metastases: initial experiences in breast cancer patients

Conventional CT scanners use energy-integrating detectors (EIDs). Photon-counting detector (PCD) computed tomography (CT) utilizes a CT detector technology based on smaller detector pixels capable of counting single photons and in addition discriminating their energy. Goal of this study was to explore the potential of higher spatial resolution for imaging of bone metastases. Four female patients with histologically confirmed breast cancer and bone metastases were included between July and October 2019. All patients underwent conventional EID CT scans followed by a high resolution non-contrast experimental PCD CT scan. Ultra-high resolution (UHR) reconstruction kernels were used to reconstruct axial slices with voxel sizes of 0.3 mm × 0.3 mm (inplane) × 1 mm (z-direction). Four radiologists blinded for patient identity assessed the images and compared the quality to conventional CT using a qualitative Likert scale. In this case series, we present images of bone metastases in breast cancer patients using an experimental PCD CT scanner and ultra-high-resolution kernels. A tendency to both a smaller inter-reader variability in the structural assessment of lesion sizes and in the readers' opinion to an improved visualization of lesion margins and content was observed. In conclusion, while further studies are warranted, PCD CT has a high potential for therapy monitoring in breast cancer

Pseudorapidity densities of charged particles with transverse momentum thresholds in pp collisions at √ s = 5.02 and 13 TeV

The pseudorapidity density of charged particles with minimum transverse momentum (pT) thresholds of 0.15, 0.5, 1, and 2 GeV/c is measured in pp collisions at the center of mass energies of √s=5.02 and 13 TeV with the ALICE detector. The study is carried out for inelastic collisions with at least one primary charged particle having a pseudorapidity (η) within 0.8pT larger than the corresponding threshold. In addition, measurements without pT-thresholds are performed for inelastic and nonsingle-diffractive events as well as for inelastic events with at least one charged particle having |η|2GeV/c), highlighting the importance of such measurements for tuning event generators. The new measurements agree within uncertainties with results from the ATLAS and CMS experiments obtained at √s=13TeV.

Λc+\Lambda^+_c production in pppp and in pp-Pb collisions at sNN\sqrt {s_{NN}}=5.02 TeV

International audienceThe production cross section of prompt $\mathrm{\Lambda_{c}^{+}}$ charm baryons was measured with the ALICE detector at the LHC at midrapidity in proton-proton (pp) and proton-lead (p-Pb) collisions at a centre-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}} = 5.02$ TeV. The $\mathrm{\Lambda_{c}^{+}}$ and $\rm {\overline{\Lambda}{}_c^-}$ baryons were reconstructed in the hadronic decay channels $\rm \Lambda_{c}^{+} \rightarrow p K^{-}\pi^{+}$ and $\rm \Lambda_{c}^{+}\to p K^{0}_{S}$ and respective charge conjugates. The measured differential cross sections as a function of transverse momentum ($p_{\rm T}$) and the $p_{\rm T}$-integrated $\mathrm{\Lambda_{c}^{+}}$ production cross section in pp and in p-Pb collisions are presented. The $\mathrm{\Lambda_{c}^{+}}$ nuclear modification factor ($R_\mathrm{pPb}$), calculated from the cross sections in pp and in p-Pb collisions, is presented and compared with the $R_\mathrm{pPb}$ of D mesons. The $\mathrm {\Lambda_{c}^{+}}/\mathrm {D^0}$ ratio is also presented and compared with the light-flavour baryon-to-meson ratios p$/\pi$ and $\Lambda /\mathrm {K^0_S}$, and measurements from other LHC experiments. The results are compared to predictions from model calculations and Monte Carlo event generators

Global polarization of Λ and Λ hyperons in Pb-Pb collisions at √ s N N = 2.76 and 5.02 TeV

The global polarization of Λ and Λ hyperons is measured for Pb-Pb collisions at √sNN = 2.76 and 5.02 TeV recorded with the ALICE at the Large Hadron Collider (LHC). The results are reported differentially as a function of collision centrality and hyperon’s transverse momentum (pT ) for the range of centrality 5–50%, 0.5 < pT < 5 GeV/c, and rapidity |y| < 0.5. The hyperon global polarization averaged for Pb-Pb collisions at √sNN = 2.76 and 5.02 TeV is found to be consistent with zero, ⟨PH⟩(%)≈0.01±0.06(stat.)±0.03(syst.) in the collision centrality range 15–50%, where the largest signal is expected. The results are compatible with expectations based on an extrapolation from measurements at lower collision energies at the Relativistic Heavy Ion Collider, hydrodynamical model calculations, and empirical estimates based on collision energy dependence of directed flow, all of which predict the global polarization values at LHC energies of the order of 0.01%

Charged-particle multiplicity fluctuations in Pb–Pb collisions at √ sNN = 2.76 TeV

Measurements of event-by-event fluctuations of charged-particle multiplicities in Pb–Pb collisionsat √sNN = 2.76 TeV using the ALICE detector at the CERN Large Hadron Collider (LHC) are presented in the pseudorapidity range |η| < 0.8 and transverse momentum 0.2 < pT < 2.0 GeV/c. The amplitude of the fluctuations is expressed in terms of the variance normalized by the mean of the multiplicity distribution. The η and pT dependences of the fluctuations and their evolution with respect to collision centrality are investigated. The multiplicity fluctuations tend to decrease from peripheral to central collisions. The results are compared to those obtained from HIJING and AMPT Monte Carlo event generators as well as to experimental data at lower collision energies. Additionally, the measured multiplicity fluctuations are discussed in the context of the isothermal compressibility of the high-density strongly-interacting system formed in central Pb–Pb collisions