Multicentre quantitative Ga-68 PET/CT performance harmonisation

Purpose Performance standards for quantitative F-18-FDG PET/CT studies are provided by the EANM Research Ltd. (EARL) to enable comparability of quantitative PET in multicentre studies. Yet, such specifications are not available for Ga-68. Therefore, our aim was to evaluate Ga-68-PET/CT quantification variability in a multicentre setting. Methods A survey across Dutch hospitals was performed to evaluate differences in clinical Ga-68 PET/CT study protocols. Ga-68 and F-18 phantom acquisitions were performed by 8 centres with 13 different PET/CT systems according to EARL protocol. The cylindrical phantom and NEMA image quality (IQ) phantom were used to assess image noise and to identify recovery coefficients (RCs) for quantitative analysis. Both phantoms were used to evaluate cross-calibration between the PET/CT system and local dose calibrator. Results The survey across Dutch hospitals showed a large variation in clinical Ga-68 PET/CT acquisition and reconstruction protocols. Ga-68 PET/CT image noise was below 10%. Cross-calibration was within 10% deviation, except for one system to overestimate F-18 and two systems to underestimate the Ga-68 activity concentration. RC-curves for F-18 and Ga-68 were within and on the lower limit of current EARL standards, respectively. After correction for local Ga-68/F-18 cross-calibration, mean Ga-68 performance was 5% below mean EARL performance specifications. Conclusions Ga-68 PET/CT quantification performs on the lower limits of the current EARL RC standards for F-18. Correction for local Ga-68/F-18 cross-calibration mismatch is advised, while maintaining the EARL reconstruction protocol thereby avoiding multiple EARL protocols

Multicenter Comparison of Molecular Tumor Boards in The Netherlands:Definition, Composition, Methods, and Targeted Therapy Recommendations

Background Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type-specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a "Dutch MTB model" for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing

TGF-β in tolerance, development and regulation of immunity

AbstractThe TGF-β superfamily is an ancient metazoan protein class which cuts across cell and tissue differentiation, developmental biology and immunology. Its many members are regulated at multiple levels from intricate control of gene transcription, post-translational processing and activation, and signaling through overlapping receptor structures and downstream intracellular messengers. We have been interested in TGF-β homologues firstly as key players in the induction of immunological tolerance, the topic so closely associated with Ray Owen. Secondly, our interests in how parasites may manipulate the immune system of their host has also brought us to study the TGF-β pathway in infections with longlived, essentially tolerogenic, helminth parasites. Finally, within the spectrum of mammalian TGF-β proteins is an exquisitely tightly-regulated gene, anti-Müllerian hormone (AMH), whose role in sex determination underpins the phenotype of freemartin calves that formed the focus of Ray’s seminal work on immunological tolerance

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions

Multicenter Comparison of Molecular Tumor Boards in The Netherlands: Definition, Composition, Methods, and Targeted Therapy Recommendations

Background: Molecular tumor boards (MTBs) provide rational, genomics-driven, patient-tailored treatment recommendations. Worldwide, MTBs differ in terms of scope, composition, methods, and recommendations. This study aimed to assess differences in methods and agreement in treatment recommendations among MTBs from tertiary cancer referral centers in The Netherlands. Materials and Methods: MTBs from all tertiary cancer referral centers in The Netherlands were invited to participate. A survey assessing scope, value, logistics, composition, decision-making method, reporting, and registration of the MTBs was completed through on-site interviews with members from each MTB. Targeted therapy recommendations were compared using 10 anonymized cases. Participating MTBs were asked to provide a treatment recommendation in accordance with their own methods. Agreement was based on which molecular alteration(s) was considered actionable with the next line of targeted therapy. Results: Interviews with 24 members of eight MTBs revealed that all participating MTBs focused on rare or complex mutational cancer profiles, operated independently of cancer type–specific multidisciplinary teams, and consisted of at least (thoracic and/or medical) oncologists, pathologists, and clinical scientists in molecular pathology. Differences were the types of cancer discussed and the methods used to achieve a recommendation. Nevertheless, agreement among MTB recommendations, based on identified actionable molecular alteration(s), was high for the 10 evaluated cases (86%). Conclusion: MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational cancer profiles. We propose a “Dutch MTB model” for an optimal, collaborative, and nationally aligned MTB workflow. Implications for Practice: Interpretation of genomic analyses for optimal choice of target therapy for patients with cancer is becoming increasingly complex. A molecular tumor board (MTB) supports oncologists in rationalizing therapy options. However, there is no consensus on the most optimal setup for an MTB, which can affect the quality of recommendations. This study reveals that the eight MTBs associated with tertiary cancer referral centers in The Netherlands are similar in setup and reach a high agreement in recommendations for rare or complex mutational profiles. The Dutch MTB model is based on a collaborative and nationally aligned workflow with interinstitutional collaboration and data sharing

Observation of the B0 → ρ0ρ0 decay from an amplitude analysis of B0 → (π+π−)(π+π−) decays

Proton–proton collision data recorded in 2011 and 2012 by the LHCb experiment, corresponding to an integrated luminosity of 3.0 fb−1 , are analysed to search for the charmless B0→ρ0ρ0 decay. More than 600 B0→(π+π−)(π+π−) signal decays are selected and used to perform an amplitude analysis, under the assumption of no CP violation in the decay, from which the B0→ρ0ρ0 decay is observed for the first time with 7.1 standard deviations significance. The fraction of B0→ρ0ρ0 decays yielding a longitudinally polarised final state is measured to be fL=0.745−0.058+0.048(stat)±0.034(syst) . The B0→ρ0ρ0 branching fraction, using the B0→ϕK⁎(892)0 decay as reference, is also reported as B(B0→ρ0ρ0)=(0.94±0.17(stat)±0.09(syst)±0.06(BF))×10−6

Angular analysis of the B-0 -> K*(0) e(+) e(-) decay in the low-q(2) region

An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions.An angular analysis of the B$^{0}$ → K^{*}^{0} e$^{+}$ e$^{−}$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 fb$^{−1}$, collected by the LHCb experiment in pp collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared (q$^{2}$) interval between 0.002 and 1.120 GeV$^{2}$ /c$^{4}$. The angular observables F$_{L}$ and A$_{T}^{Re}$ which are related to the K^{*}^{0} polarisation and to the lepton forward-backward asymmetry, are measured to be F$_{L}$ = 0.16 ± 0.06 ± 0.03 and A$_{T}^{Re}$  = 0.10 ± 0.18 ± 0.05, where the first uncertainty is statistical and the second systematic. The angular observables A$_{T}^{(2)}$ and A$_{T}^{Im}$ which are sensitive to the photon polarisation in this q$^{2}$ range, are found to be A$_{T}^{(2)}$  = − 0.23 ± 0.23 ± 0.05 and A$_{T}^{Im}$  = 0.14 ± 0.22 ± 0.05. The results are consistent with Standard Model predictions.An angular analysis of the $B^0 \rightarrow K^{*0} e^+ e^-$ decay is performed using a data sample, corresponding to an integrated luminosity of 3.0 {\mbox{fb}^{-1}}, collected by the LHCb experiment in $pp$ collisions at centre-of-mass energies of 7 and 8 TeV during 2011 and 2012. For the first time several observables are measured in the dielectron mass squared ($q^2$) interval between 0.002 and 1.120${\mathrm{\,Ge\kern -0.1em V^2\!/}c^4}$. The angular observables $F_{\mathrm{L}}$ and $A_{\mathrm{T}}^{\mathrm{Re}}$ which are related to the $K^{*0}$ polarisation and to the lepton forward-backward asymmetry, are measured to be $F_{\mathrm{L}}= 0.16 \pm 0.06 \pm0.03$ and $A_{\mathrm{T}}^{\mathrm{Re}} = 0.10 \pm 0.18 \pm 0.05$, where the first uncertainty is statistical and the second systematic. The angular observables $A_{\mathrm{T}}^{(2)}$ and $A_{\mathrm{T}}^{\mathrm{Im}}$ which are sensitive to the photon polarisation in this $q^2$ range, are found to be $A_{\mathrm{T}}^{(2)} = -0.23 \pm 0.23 \pm 0.05$ and $A_{\mathrm{T}}^{\mathrm{Im}} =0.14 \pm 0.22 \pm 0.05$. The results are consistent with Standard Model predictions

A study of CP violation in B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays with D -> (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes