Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated in a continuous manner on a number of compounds using a range of processing technologies and scales. Whilst basic design principles for crystallisations and continuous processes are known, applying these in the context of rapid pharmaceutical process development with the associated constraints of speed to market and limited material availability is challenging. A systematic approach for continuous crystallisation process design is required to avoid the risk that decisions made on one aspect of the process conspire to make a later development step or steps, either for crystallisation or another unit operation, more difficult. In response to this industry challenge, an innovative system-wide approach to decision making has been developed to support rapid, systematic, and efficient continuous seeded cooling crystallisation process design. For continuous crystallisation, the goal is to develop and operate a robust, consistent process with tight control of particle attributes. Here, an innovative system-based workflow is presented that addresses this challenge. The aim, methodology, key decisions and output at each at stage are defined and a case study is presented demonstrating the successful application of the workflow for the rapid design of processes to produce kilo quantities of product with distinct, specified attributes suited to the pharmaceutical development environment. This work concludes with a vision for future applications of workflows in continuous manufacturing development to achieve rapid performance based design of pharmaceuticals

MI 48084-5353 (formerly Technical Fellow at General Motors Research), [email protected]. John R. Hauser is the Kirin Professor of Marketing

Abstract Morphing enables a website to learn (actively and near optimally) which banner advertisements to serve to each cognitive-style segment in order to maximize outcome measures such as click-through, brand consideration, or purchase. Consumer segments are identified automatically from consumers' clickstream choices. Morphing works best on high-traffic websites with tens of thousands of visitors because large samples are necessary to reach steady state optimally. This paper describes the first large-sample random-assignment field test of banner morphing -over 100,000 consumers viewing over 450,000 banners on CNET.com. (Previously published morphing evaluations evaluated morphing website characteristics and were based on predictive simulations using only priming-study data.) On relevant webpages, CNET's clickthrough rates almost double relative to control banners. We supplement the CNET field test with a focused experiment on an automotive information-and-recommendation website. The focused experiment replaces automated learning with a longitudinal design which tests the premise of morph-to-segment matching. Banners matched to cognitive styles, as well as the stage of the consumer's buying process and body-type preference, significantly increase click-through rates, brand consideration, and purchase likelihood relative to a control

MI 48084-5353 (formerly Technical Fellow at General Motors Research), [email protected]. John R. Hauser is the Kirin Professor of Marketing

Abstract Researchers and practitioners devote substantial effort to targeting banner advertisements, but less effort on how to communicate with consumers once targeted. Morphing enables a website to learn (actively and near optimally) which banner advertisements to serve to each cognitive-style segment in order to maximize click-through, brand consideration, and purchase. Cognitive-style segments are identified automatically from consumers' clickstreams. This paper describes the first large-sample random-assignment field-test of banner morphing -over 100,000 consumers viewing over 450,000 banners on CNET.com. On relevant webpages, CNET's click-through rates almost doubled relative to control banners. We supplement the CNET field test with a focused experiment on an automotive information-andrecommendation website. The focused experiment replaces automated learning with a longitudinal design to test the premise of morph-to-segment matching. Banners matched to cognitive styles, as well as the stage of the consumer's buying process and body-type preference, significantly increase click-through rates, brand consideration, and purchase likelihood relative to a control. Together the field and the focused experiments demonstrate that matching cognitive styles provide significant benefits above and beyond more-traditional targeting. Such improved banner effectiveness has strategic implications for allocations among media

Observation of abnormal suppression of f0\mathrm{f}_{0}(980) production in p−-Pb collisions at sNN\sqrt{s_{\rm NN}} = 5.02 TeV

International audienceThe dependence of $\mathrm{f}_{0}$(980) production on the final-state charged-particle multiplicity in p$-$Pb collisions at $\sqrt{s_{\mathrm{NN}}} = 5.02$ TeV is reported. The production of $\mathrm{f}_{0}$(980) is measured with the ALICE detector via the $\mathrm{f}_0 (980) \rightarrow \pi^{+}\pi^{-}$ decay channel in a midrapidity region of $-0.5<y<0$. Particle yield ratios of $\mathrm{f}_{0}$(980) to $\pi$ and $\mathrm{K}^{*}$(892)$^{0}$ are found to be decreasing with increasing charged-particle multiplicity. The magnitude of the suppression of the $\mathrm{f}_{0}$(980)/$\pi$ and $\mathrm{f}_{0}$(980)/$\mathrm{K}^{*}$(892)$^{0}$ yield ratios is found to be dependent on the transverse momentum $p_{\mathrm{T}}$, suggesting different mechanisms responsible for the measured effects. Furthermore, the nuclear modification factor $Q_{\mathrm{pPb}}$ of $\mathrm{f}_{0}$(980) is measured in various multiplicity ranges. The $Q_{\mathrm{pPb}}$ shows a strong suppression of the $\mathrm{f}_{0}$(980) production in the $p_{\mathrm{T}}$ region up to about 4 GeV/$c$. The results on the particle yield ratios and $Q_{\mathrm{pPb}}$ for $\mathrm{f}_{0}$(980) may help to understand the late hadronic phase in p$-$Pb collisions and the nature of the internal structure of $\mathrm{f}_{0}$(980) particle

Common femtoscopic hadron-emission source in pp collisions at the LHC

International audienceThe femtoscopic study of pairs of identical pions is particularly suited to investigate the effective source function of particle emission, due to the resulting Bose-Einstein correlation signal. In small collision systems at the LHC, pp in particular, the majority of the pions are produced in resonance decays, which significantly affect the profile and size of the source. In this work, we explicitly model this effect in order to extract the primordial source in pp collisions at $\sqrt{s} = 13$ TeV from charged $\pi$-$\pi$ correlations measured by ALICE. We demonstrate that the assumption of a Gaussian primordial source is compatible with the data and that the effective source, resulting from modifications due to resonances, is approximately exponential, as found in previous measurements at the LHC. The universality of hadron emission in pp collisions is further investigated by applying the same methodology to characterize the primordial source of K-p pairs. The size of the primordial source is evaluated as a function of the transverse mass ($m_{\rm T}$) of the pairs, leading to the observation of a common scaling for both $\pi$-$\pi$ and K-p, suggesting a collective effect. Further, the present results are compatible with the $m_{\rm T}$ scaling of the p-p and p$-\Lambda$ primordial source measured by ALICE in high multiplicity pp collisions, providing compelling evidence for the presence of a common emission source for all hadrons in small collision systems at the LHC. This will allow the determination of the source function for any hadron--hadron pairs with high precision, granting access to the properties of the possible final-state interaction among pairs of less abundantly produced hadrons, such as strange or charmed particles

Exclusive four pion photoproduction in ultraperipheral Pb-Pb collisions at sNN=5.02\sqrt{s_{\rm NN}} = 5.02 TeV

International audienceThe intense photon fluxes from relativistic nuclei provide an opportunity to study photonuclear interactions in ultraperipheral collisions. The measurement of coherently photoproduced $\pi^+\pi^-\pi^+\pi^-$ final states in ultraperipheral Pb-Pb collisions at $\sqrt{s_{\mathrm{NN}}}=5.02$ TeV is presented for the first time. The cross section, d$\sigma$/d$y$, times the branching ratio ($\rho\rightarrow \pi^+ \pi^+ \pi^- \pi^-$) is found to be $47.8\pm2.3~\rm{(stat.)}\pm7.7~\rm{(syst.)}$ mb in the rapidity interval $|y| < 0.5$. The invariant mass distribution is not well described with a single Breit-Wigner resonance. The production of two interfering resonances, $\rho(1450)$ and $\rho(1700)$, provides a good description of the data. The values of the masses ($m$) and widths ($\Gamma$) of the resonances extracted from the fit are $m_{1}=1385\pm14~\rm{(stat.)}\pm3~\rm{(syst.)}$ MeV/$c^2$, $\Gamma_{1}=431\pm36~\rm{(stat.)}\pm82~\rm{(syst.)}$ MeV/$c^2$, $m_{2}=1663\pm13~\rm{(stat.)}\pm22~\rm{(syst.)}$ MeV/$c^2$ and $\Gamma_{2}=357 \pm31~\rm{(stat.)}\pm49~\rm{(syst.)}$ MeV/$c^2$, respectively. The measured cross sections times the branching ratios are compared to recent theoretical predictions

Systematic study of flow vector decorrelation in sNN=5.02\mathbf{\sqrt{\textit{s}_{_{\bf NN}}}=5.02} TeV Pb-Pb collisions

International audienceMeasurements of the $p_{\rm T}$-dependent flow vector fluctuations in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}} = 5.02~\mathrm{TeV}$ using azimuthal correlations with the ALICE experiment at the LHC are presented. A four-particle correlation approach [1] is used to quantify the effects of flow angle and magnitude fluctuations separately. This paper extends previous studies to additional centrality intervals and provides measurements of the $p_{\rm T}$-dependent flow vector fluctuations at $\sqrt{s_{_{\rm NN}}} = 5.02~\mathrm{TeV}$ with two-particle correlations. Significant $p_{\rm T}$-dependent fluctuations of the $\vec{V}_{2}$ flow vector in Pb-Pb collisions are found across different centrality ranges, with the largest fluctuations of up to $\sim$15% being present in the 5% most central collisions. In parallel, no evidence of significant $p_{\rm T}$-dependent fluctuations of $\vec{V}_{3}$ or $\vec{V}_{4}$ is found. Additionally, evidence of flow angle and magnitude fluctuations is observed with more than $5\sigma$ significance in central collisions. These observations in Pb-Pb collisions indicate where the classical picture of hydrodynamic modeling with a common symmetry plane breaks down. This has implications for hard probes at high $p_{\rm T}$, which might be biased by $p_{\rm T}$-dependent flow angle fluctuations of at least 23% in central collisions. Given the presented results, existing theoretical models should be re-examined to improve our understanding of initial conditions, quark--gluon plasma (QGP) properties, and the dynamic evolution of the created system

Measurement of Ωc0\Omega^0_{\rm c} baryon production and branching-fraction ratio BR(Ωc0→Ω−e+νe)/BR(Ωc0→Ω−π+){\rm BR(\Omega^0_c \rightarrow \Omega^- e^+\nu_e)} / {\rm BR(\Omega^0_c \rightarrow \Omega^- \pi^+)} in pp collisions at s\sqrt{s} = 13 TeV

International audienceThe inclusive production of the charm-strange baryon $\Omega^{0}_{\rm c}$ is measured for the first time via its semileptonic decay into $\Omega^{-}\rm e^{+}\nu_{e}$ at midrapidity ($|y|<0.8$) in proton$-$proton (pp) collisions at the centre-of-mass energy $\sqrt{s}=13$ TeV with the ALICE detector at the LHC. The transverse momentum ($p_{\rm T}$) differential cross section multiplied by the branching ratio is presented in the interval $2<p_{\rm T}<12~{\rm GeV}/c$. The branching-fraction ratio ${\rm BR}(\Omega^0_{\rm c} \rightarrow \Omega^{-}{\rm e}^{+}\nu_{\rm e})/ {\rm BR}(\Omega^0_{\rm c} \rightarrow \Omega^{-}{\pi}^{+})$ is measured to be 1.12 $\pm$ 0.22 (stat.) $\pm$ 0.27 (syst.). Comparisons with other experimental measurements, as well as with theoretical calculations, are presented

Measurement of the production cross section of prompt Ξc0\Xi^0_{\rm c} baryons in p−-Pb collisions at sNN = 5.02\sqrt{s_{\mathrm{NN}}}~=~5.02 TeV

International audienceThe transverse momentum ($p_{\rm T}$) differential production cross section of the promptly-produced charm-strange baryon $\Xi_{\rm c}^{0}$ (and its charge conjugate $\overline{\Xi_{\rm c}^{0}}$) is measured at midrapidity via its hadronic decay into ${\rm \pi^{+}}\Xi^{-}$ in p$-$Pb collisions at a centre-of-mass energy per nucleon$-$nucleon collision $\sqrt{s_{\mathrm{NN}}}~=~5.02$ TeV with the ALICE detector at the LHC. The $\Xi_{\rm c}^{0}$ nuclear modification factor ($R_{\rm pPb}$), calculated from the cross sections in pp and p$-$Pb collisions, is presented and compared with the $R_{\rm pPb}$ of $\Lambda_{\rm c}^{+}$ baryons. The ratios between the $p_{\rm T}$-differential production cross section of $\Xi_{\rm c}^{0}$ baryons and those of $\mathrm {D^0}$ mesons and $\Lambda_{\rm c}^{+}$ baryons are also reported and compared with results at forward and backward rapidity from the LHCb Collaboration. The measurements of the production cross section of prompt $\Xi^0_{\rm c}$ baryons are compared with a model based on perturbative QCD calculations of charm-quark production cross sections, which includes only cold nuclear matter effects in p$-$Pb collisions, and underestimates the measurement by a factor of about 50. This discrepancy is reduced when the data is compared with a model in which hadronisation is implemented via quark coalescence. The $p_{\rm T}$-integrated cross section of prompt $\Xi^0_{\rm c}$-baryon production at midrapidity extrapolated down to $p_{\rm T}$ = 0 is also reported. These measurements offer insights and constraints for theoretical calculations of the hadronisation process. Additionally, they provide inputs for the calculation of the charm production cross section in p$-$Pb collisions at midrapidity

Addendum: Dielectron production in proton-proton and proton-lead collisions at sNN\sqrt{s_{\rm NN}} = 5.02 TeV

International audienceThis is an addendum to the article [arXiv:2005.11995] "Dielectron production in proton-proton and proton-lead collisions at $\sqrt{s_{\mathrm{NN}}}$ = 5.02 TeV" published in Phys. Rev. C 102 no. 5, (2020) 055204. We update the extracted charm cross section at midrapidity given in Table 3 and Figure 4 (left) of the original publication with the fragmentation fractions of charm quarks in pp collisions published in Phys. Rev. D 105 (2022) L011103