A European Turn in Early American History? A Discussion of Evan Haefeli's Accidental Pluralism: America and the Religious Politics of English Expansion, 1497-1662

From the nineteenth century onwards, Americans have naturalized their colonial origins into a consensual nationalist history, emphasizing America’s perceived role as a refuge for the persecuted, while smoothing out a myriad of complexities in the process. Evan Haefeli attempts to overturn the assumptions underpinning this narrative and is convinced that many important aspects of early America need to be understood within a broader European context. In Accidental Pluralism, he argues that the collapse of religious unity in England lies at the root of the emergence of pluralism in colonial America, in which he includes Canada and the Caribbean. Relationships among states, churches, and publics were contested from the earliest decades of colonization and created a pluralistic religious landscape that no one had anticipated. The four reviewers are fulsome in their praise, calling it an impressive, important, powerful, and sweeping book that few scholars could have written. The reviewers also raise questions, for instance by problematizing the incorporation of the colonial American dimension into early British history, criticizing the validity of the chosen end date, and questioning his definitions of diversity, pluralism, and religious toleration. In his response Evan Haefeli takes the opportunity to reflect on what drove him to write the book and to organize it in this way. He acknowledges that connecting early American history with its broader European context was more difficult than it should have been, as the dominant questions in the two historiographies are an ocean apart. While the argument of the book is aimed at early Americanists, Haefeli is grateful that the reviewers situate the story he tells within the broader early modern European history of toleration

Assessing the perspective of well-being of older patients with multiple morbidities by using the LAVA tool-a person-centered approach

BACKGROUND: Older patients with multiple morbidities are a particularly vulnerable population that is likely to face complex medical decisions at some time in their lives. A patient-centered medical care fosters the inclusion of the patients’ perspectives, priorities, and complaints into clinical decision making. METHODS: This article presents a short and non-normative assessment tool to capture the priorities and problems of older patients. The so-called LAVA (“Life and Vitality Assessment”) tool was developed for practical use in seniors in the general population and for residents in nursing homes in order to gain more knowledge about the patients themselves as well as to facilitate access to the patients. The LAVA tool conceptualizes well-being from the perspectives of older individuals themselves rather than from the perspectives of outside individuals. RESULTS: The LAVA tool is graphically presented and the assessment is explained in detail. Exemplarily, the outcomes of the assessments with the LAVA of three multimorbid older patients are presented and discussed. In each case, the assessment pointed out resources as well as at least one problem area, rated as very important by the patients themselves. CONCLUSIONS: The LAVA tool is a short, non-normative, and useful approach that encapsulates the perspectives of well-being of multimorbid patients and gives insights into their resources and problem areas. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-021-02342-3

Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer

BACKGROUND: The investigational oral DNA vaccine VXM01 targets the vascular endothelial growth factor receptor 2 (VEGFR-2) and uses Salmonella typhi Ty21a as a vector. The immune reaction elicited by VXM01 is expected to disrupt the tumor neovasculature and, consequently, inhibit tumor growth. VXM01 potentially combines the advantages of anti-angiogenic therapy and active immunotherapy. METHODS/DESIGN: This phase I trial examines the safety, tolerability, and immunological and clinical responses to VXM01. The randomized, placebo-controlled, double blind dose-escalation study includes up to 45 patients with locally advanced and stage IV pancreatic cancer. The patients will receive four doses of VXM01 or placebo in addition to gemcitabine as standard of care. Doses from 10(6) cfu up to 10(10) cfu of VXM01 will be evaluated in the study. An independent data safety monitoring board (DSMB) will be involved in the dose-escalation decisions. In addition to safety as primary endpoint, the VXM01-specific immune reaction, as well as clinical response parameters will be evaluated. DISCUSSION: The results of this study shall provide the first data regarding the safety and immunogenicity of the oral anti-VEGFR-2 vaccine VXM01 in cancer patients. They will also define the recommended dose for phase II and provide the basis for further clinical evaluation, which may also include additional cancer indications. TRIAL REGISTRATION: EudraCT No.: 2011-000222-29, NCT01486329, ISRCTN6880927

Analytical Performance Evaluation of New DESI Enhancements for Targeted Drug Quantification in Tissue Sections

Desorption/ionization (DI)-mass spectrometric (MS) methods offer considerable advantages of rapidity and low-sample input for the analysis of solid biological matrices such as tissue sections. The concept of desorption electrospray ionization (DESI) offers the possibility to ionize compounds from solid surfaces at atmospheric pressure, without the addition of organic compounds to initiate desorption. However, severe drawbacks from former DESI hardware stability made the development of assays for drug quantification difficult. In the present study, the potential of new prototype source setups (High Performance DESI Sprayer and Heated Transfer Line) for the development of drug quantification assays in tissue sections was evaluated. It was demonstrated that following dedicated optimization, new DESI XS enhancements present promising options regarding targeted quantitative analyses. As a model compound for these developments, ulixertinib, an inhibitor of extracellular signal-regulated kinase (ERK) 1 and 2 was used

Performance of the LHCb muon system

The performance of the LHCb Muon system and its stability across the full 2010 data taking with LHC running at ps = 7 TeV energy is studied. The optimization of the detector setting and the time calibration performed with the first collisions delivered by LHC is described. Particle rates, measured for the wide range of luminosities and beam operation conditions experienced during the run, are compared with the values expected from simulation. The space and time alignment of the detectors, chamber efficiency, time resolution and cluster size are evaluated. The detector performance is found to be as expected from specifications or better. Notably the overall efficiency is well above the design requirementsComment: JINST_015P_1112 201

Performance of the LHCb vertex locator

The Vertex Locator (VELO) is a silicon microstrip detector that surrounds the proton-proton interaction region in the LHCb experiment. The performance of the detector during the first years of its physics operation is reviewed. The system is operated in vacuum, uses a bi-phase CO2 cooling system, and the sensors are moved to 7 mm from the LHC beam for physics data taking. The performance and stability of these characteristic features of the detector are described, and details of the material budget are given. The calibration of the timing and the data processing algorithms that are implemented in FPGAs are described. The system performance is fully characterised. The sensors have a signal to noise ratio of approximately 20 and a best hit resolution of 4 μm is achieved at the optimal track angle. The typical detector occupancy for minimum bias events in standard operating conditions in 2011 is around 0.5%, and the detector has less than 1% of faulty strips. The proximity of the detector to the beam means that the inner regions of the n+-on-n sensors have undergone space-charge sign inversion due to radiation damage. The VELO performance parameters that drive the experiment's physics sensitivity are also given. The track finding efficiency of the VELO is typically above 98% and the modules have been aligned to a precision of 1 μm for translations in the plane transverse to the beam. A primary vertex resolution of 13 μm in the transverse plane and 71 μm along the beam axis is achieved for vertices with 25 tracks. An impact parameter resolution of less than 35 μm is achieved for particles with transverse momentum greater than 1 GeV/c

Precision luminosity measurements at LHCb

Measuring cross-sections at the LHC requires the luminosity to be determined accurately at each centre-of-mass energy √s. In this paper results are reported from the luminosity calibrations carried out at the LHC interaction point 8 with the LHCb detector for √s = 2.76, 7 and 8 TeV (proton-proton collisions) and for √sNN = 5 TeV (proton-lead collisions). Both the "van der Meer scan" and "beam-gas imaging" luminosity calibration methods were employed. It is observed that the beam density profile cannot always be described by a function that is factorizable in the two transverse coordinates. The introduction of a two-dimensional description of the beams improves significantly the consistency of the results. For proton-proton interactions at √s = 8 TeV a relative precision of the luminosity calibration of 1.47% is obtained using van der Meer scans and 1.43% using beam-gas imaging, resulting in a combined precision of 1.12%. Applying the calibration to the full data set determines the luminosity with a precision of 1.16%. This represents the most precise luminosity measurement achieved so far at a bunched-beam hadron collider

Observation of two new Ξb−\Xi_b^- baryon resonances

Two structures are observed close to the kinematic threshold in the $\Xi_b^0 \pi^-$ mass spectrum in a sample of proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb$^{-1}$ recorded by the LHCb experiment. In the quark model, two baryonic resonances with quark content $bds$ are expected in this mass region: the spin-parity $J^P = \frac{1}{2}^+$ and $J^P=\frac{3}{2}^+$ states, denoted $\Xi_b^{\prime -}$ and $\Xi_b^{*-}$. Interpreting the structures as these resonances, we measure the mass differences and the width of the heavier state to be $m(\Xi_b^{\prime -}) - m(\Xi_b^0) - m(\pi^{-}) = 3.653 \pm 0.018 \pm 0.006$ MeV$/c^2$, $m(\Xi_b^{*-}) - m(\Xi_b^0) - m(\pi^{-}) = 23.96 \pm 0.12 \pm 0.06$ MeV$/c^2$, $\Gamma(\Xi_b^{*-}) = 1.65 \pm 0.31 \pm 0.10$ MeV, where the first and second uncertainties are statistical and systematic, respectively. The width of the lighter state is consistent with zero, and we place an upper limit of $\Gamma(\Xi_b^{\prime -}) < 0.08$ MeV at 95% confidence level. Relative production rates of these states are also reported.Comment: 17 pages, 2 figure

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date