Artículos de revistas sobre el tema "222/.506"

Objective. To study the prevalence of thrombosis allelic polymorphisms in patients with severe angina who have indications for myocardial revascularization. Design and methods. The study included 105 patients (87 men and 18 women) aged from 33 to 70 years who had angina III–IV functional class, with indications for myocardial revascularization. All the patients studied polymorphism of the inhibitor of tissue plasminogen activator I type (675 4G/5G) (PAI-I), mutations of the factor II-prothrombin (20210 G / A), mutations of the factor V Leiden (Arg 506 Gln) and polymorphism of the methylenetetrahydrofolate reductase (Ala 222 Val) (MTHFR). Results. The prevalence of these mutations and polymorphisms in patients with severe angina requiring revascularization of the myocardium in 3 times greater than in the group of healthy adolescents. Our data showed that the risk of severe angina is directly proportional, and the age of the clinical debut of CHD is inversely proportional to the number of studied genetic defects. Thrombophilic polymorphisms studied genes increases the effects of other cardiovascular risk factors such as male sex, smoking and leads to an earlier debut of clinical CHD. Conclusion. It is necessary to form the strategy of genetically-based population policy for the prevention of atherosclerosis, including coronary. Healthy persons with diagnosed thrombosis polymorphisms are need of active primary prevention of cardiovascular disease.

In the nineties, cattle stocks gradually decreased from 3 506 222 head of cattle in 1990 to 1 657 337 head in 1999. Skin testing of cattle was carried out annually using bovine tuberculin. Animals for sale were also simultaneously tested with avian tuberculin. In records from 1991 to 1999 a total of 14 611 393 bovine tuberculin skin tests and 611 405 simultaneous avian tuberculin skin tests are registered. A total of 1 457 (0.01%) animals reacted positively with bovine tuberculin and 1 790 (0.29%) with avian tuberculin. In the period monitored a total of 7 268 274 head of cattle were slaughtered and given veterinary hygienic examinations. Statistical data on the post-mortem detection of tuberculous lesions have been available for nine years since 1992 when tuberculous lesions were found in 1 186 (0.019%) out of 6 273 441 slaughtered animals. Mycobacteria were isolated from the organs of only 561 (17.5%) out of 3 202 culturally examined animals. M. bovis only was isolated from 48 (8.6%) animals originating from seven herds (two infected herds in 1991, 1992 and 1994 and one infected herd in 1995): four outbreaks were detected by annual skin testing, one outbreak by movement tuberculin skin testing and two outbreaks by the detection of tuberculous lesions at slaughter. M. avium complex strains of serotypes 1, 2 and 3 and of genotypes IS901+ and IS1245+ were isolated from 331 (59.0%) animals and strains of serotypes 4 to 6, 8 to 11 and 21 and of genotypes IS901- and IS1245+ were isolated from 132 (23.5%) animals. Potentially pathogenic bacteria of the M. chelonae, M. terrae, M. phlei and M. fortuitum species were isolated from 50 (8.9%) animals. Neither miliary nor generalised tuberculosis was found in any of the animals. Between 1996 and 1999, the proportion of cattle in which tuberculous lesions were recorded decreased.

Abstract MCL1 is an anti-apoptotic protein inhibiting cancer cell death. It is frequently amplified or overexpressed in cancer and confers resistance to relevant standard of care. Therefore, MCL1 is an attractive target to potentially re-sensitize tumors to conventional chemotherapy and targeted agents. Here we describe ANJ810 as a novel, potent, and selective MCL1 inhibitor which specifically induces apoptosis in cancer cells. ANJ810 potently and reversibly binds to the BH3-binding groove of human MCL1 (KD = 0.3 nM), thereby inhibiting the interaction with the BH3-only protein NOXA (IC50 = 0.4 nM). ANJ810 shows a 4-log-fold greater selectivity to MCL1 over other anti-apoptotic proteins like Bcl-xL or Bcl-2. In cells, ANJ810 treatment rapidly (< 15 min) disrupts the MCL1-BAK interaction with an IC50 < 10 nM, resulting in caspase-3 activation and cancer cell death. Knockout of BAK and BAX completely rescues cells from ANJ810 induced killing, indicating that initiation of cell death occurs through the intrinsic apoptotic pathway. Screening over 750 cell lines (PRISM), we found that ANJ810 induced anti-cancer activity in 222 cell lines with an IC50 < 1 μM across multiple solid and hematological cancers, including breast, lung, melanoma, sarcoma, lymphoma, and leukemia. The top genomic feature that correlates with sensitivity to ANJ810 treatment is the ratio of Bcl-xL/BAK expression. A key design principle of ANJ810 is its rapid systemic clearance to potentially minimize exposure-driven toxicities associated with MCL1 inhibition. ANJ810 induces efficient cancer cell killing within 4 hours in vitro but has no impact on cell viability or troponin I release in hiPSC-derived cardiomyocytes at supra-pharmacologic concentrations. In vivo, i.v. bolus injections of ANJ810 lead to short plasma residence time, yet are efficacious in xenograft models of multiple myeloma, DLBCL, NSCLC and HCC. ANJ810 will test the hypothesis in human clinical trials that short-term inhibition of MCL1 can overcome tumor resistance with an acceptable safety profile to improve current standard of care. Citation Format: Ulrike Rauh, Guo Wei, Michael Serrano-Wu, Georgios Kosmidis, Stefan Kaulfuss, Franziska Siegel, Kai Thede, James McFarland, Christopher Lemke, Nicolas Werbeck, Katrin Nowak-Reppel, Sabine Pillari, Stephan Menz, Matthias Ocker, Brian Hubbard, Virendar Kaushik, Karl Ziegelbauer, Todd Golub. ANJ810 is a highly selective novel MCL1 inhibitor with optimized in vivo clearance showing robust efficacy in preclinical solid and hematological tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 506.

Abstract Background In the recent International Prognostic Score for Thrombosis in essential thrombocythemia (IPSET-thrombosis), age and history of thrombosis were confirmed as independent risk factors for future thrombosis and the study also identified independent prothrombotic role for cardiovascular (CV) risk factors and JAK2 V617F mutation (Barbui et al. Blood 2012). Methods In the current study, we re-analyzed the original IPSET-thrombosis data in 1019 patients with WHO-defined ET in whom JAK2 mutational status was available, in order to quantify the individual contributions of JAK2 mutations and CV risk factors in conventionally-assigned low and high risk ET, as well as in age- versus thrombosis-defined high risk status. Results After a median follow-up of 6.8 and 5.0 years in conventionally-assigned low- and high-risk patients, respectively, the overall annual rate of total thrombosis (108 events) in conventionally-assigned low- and high-risk patients was 1.11%-pt/y (CI 0.81-1.52) and 2.46%-pt/y (CI 1.94-3.11) respectively (p=0.001), and the difference was mainly due to a higher frequency of arterial thrombosis in high-risk patients (p<0.001).The influence of JAK2 mutational status and CV-risk factors on the rate of thrombosis in conventionally assigned low- and high-risk groups is presented in the table. Table 1. Additional risk factors N (%) Event Rate % pts/yr (95% CI) P-value P-value P-value trend Low risk 506 (50) 39 1.11 (0.81-1.52) None 200 (40) 7 0.44 (0.21-0.92) ref Cardiovascular risk factor 36 (7) 3 1.05 (0.34-3.25) 0.220 0.227 JAK2V617F 213 (43) 21 1.59 (1.04-2.44) 0.001 0.217 Both 52 (10) 8 2.57 (1.29-5.15) <0.001 ref <0.001 High risk 513 (50) 69 2.46 (1.94-3.11) None 111 (22) 10 1.44 (0.78-2.68) ref Cardiovascular risk factor 44 (9) 4 1.64 (0.62-4.37) 0.909 0.067 JAK2V617F 222 (43) 30 2.36 (1.65-3.38) 0.168 0.082 Both 136 (27) 25 4.17 (2.82-6.17) 0.011 ref 0.005 The number of major arterial and venous thrombosis was reported as rates per 100 patient-years and the difference among groups was assessed by Mantel Cox log-rank test i) Conventionally-assigned low-risk group. Amongst 506 patients, 200 (40%) displayed neither JAK2 mutation nor CV risk factors and their annual rate of thrombosis was 0.44%, as opposed to 1.05% in the presence of CV risk factors (P=NS), 1.59% in the presence of JAK2 mutation (p=0.001) and 2.57% in the presence of both CV risk factors and JAK2 mutation (P<0.001). There was no significant difference when low-risk patients with both JAK2 mutation and CV risk factors were compared with either those with CV risk factors only (p=0.227) or those with JAK2 mutation only (p=0.217). ii) Conventionally assigned high-risk group: The absence or presence of one or both of the aforementioned additional risk factors for thrombosis were documented in 111 (22%), 44 (9%), 222 (43%) and 136 (27%) patients, respectively, with corresponding annual rates of thrombosis at 1.44%, 1.64%, 2.36% and 4.17% (Table). High-risk patients with both risk factors had a significantly higher risk of thrombosis compared to their counterparts with the absence of JAK2 mutations and CV risk factors (p=0.011). Additional analysis revealed limited enhancement of thrombosis risk by either JAK2 mutations or CV risk factors or both in patients whose high-risk status was defined by the presence of thrombosis history, regardless of age (P=NS). In contrast, the presence of JAK2 mutations, with or without CV risk factors, might have affected thrombosis risk in patients where high-risk status was defined by age alone (p=0.05). Conclusions The current study suggests the possibility of considering four risk categories in ET: "very low risk" group (age ≤60 years and without thrombosis history, JAK2 mutations or CV risk factors); "low risk" (age ≤60 years and without thrombosis history but with JAK2 mutations or CV risk factors); "intermediate risk" (age>60 years but without thrombosis history or JAK2 mutations); and "high risk" (thrombosis history at any age or JAK2 -mutated patients who are older than 60 years of age). Treatment recommendations for each one of the above-mentioned new risk categories should be examined in the context of prospective controlled studies. Disclosures Barbui: Novartis: Speakers Bureau. Vannucchi:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shire: Speakers Bureau; Baxalta: Membership on an entity's Board of Directors or advisory committees. Buxhofer-Ausch:AOP Orphan: Research Funding. De Stefano:Novartis: Research Funding, Speakers Bureau; Janssen Cilag: Research Funding; Shire: Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Bruno Farmaceutici: Research Funding; Roche: Research Funding; Amgen: Speakers Bureau; Celgene: Speakers Bureau. Gisslinger:Janssen Cilag: Honoraria, Speakers Bureau; AOP ORPHAN: Consultancy, Honoraria, Research Funding, Speakers Bureau; Geron: Consultancy; Sanofi Aventis: Consultancy; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau.

Abstract Background: Many factors influence the choice of salvage therapy in relapsed/refractory multiple myeloma (RRMM), including various disease characteristics such as light chain and heavy chain subtypes. Patients with light chain only myeloma are a biologically and phenotypically distinct subset of patients from those with IgG, IgA, IgM, or IgD disease. Evidence exists that the presence of different paraprotein heavy and light chain subtypes may affect treatment outcomes. We investigated the effect of the presence of paraprotein heavy and light chain types on the efficacy and safety of pegylated liposomal doxorubicin (PLD) + bortezomib (B) versus B alone based on the phase III randomized trial of PLD+B vs. B alone in RRMM, which demonstrated improved time to progression (TTP) with PLD+B (Orlowski, JCO 2007). Methods: Eligible patients were randomized to bolus IV B 1.3 mg/m2 on days 1, 4, 8, and 11 of each 3-week cycle (n=322) or to the same B regimen plus IV PLD 30 mg/m2 on day 4 (n=324) of each cycle. The subsets of patients with light chain and heavy chain multiple myeloma subtypes were analyzed retrospectively. Results: The presence of light chain myeloma was observed in 77 patients. Few patients had IgM/IgD subtype myeloma (4 and 6 patients, respectively), while the majority of patients had IgG (n=379) or IgA (n=265) subtypes. Time to disease progression (TTP) and complete response (CR) + partial response (PR) rates for PLD+B vs B alone in patients with light chain, IgG, and IgA myeloma subtypes are listed in the table. PLD+B B P valueb Hazard Ratioc a. Based on Kaplan-Meier product-limit estimates. b. Based on stratified Log-rank test. c. A hazard ratio &gt;1 indicates an advantage for PLD+B. d. Cochran-Mantel-Haenszel test controlling for Beta2 microglobulin and response to initial treatment. Light chain, N 40 37 TTP, Median days (95% CI)a 276 (171, n/a) 117 (85, 173) .003 3.09 (1.42, 6.73) Total CR+PR, n/evaluable (%) 22/39 (56) 10/33 (30) .030d IgG subtype, N 182 197 TTP 282 (221, 331) 199 (170, 222) .002 1.67 (1.20, 2.31) Total CR+PR 70/173 (41) 81/194 (42) .915d IgA subtype, N 88 77 TTP 250 (218, n/a) 205 (177, 236) .506 1.22 (0.68, 2.18) Total CR+PR 46/79 (58) 39/72 (54) .723d Results showed that the combination of PLD+B had significant benefit over B alone in TTP (PLD+B led to longer TTP than B alone) for IgG paraprotein and light chain subtypes. Safety profiles for the 2 regimens in these subsets of patients with heavy or light chain myeloma were consistent with the known toxicities of the 2 agents used. Conclusions: These data demonstrate that the combination of PLD+B is an important treatment option in patients with RRMM. Patients with light chain only disease had the largest incremental benefit from the addition of PLD with an absolute increase in TTP of 159 days as well as an increase in the overall response rate from 30% to 56%.

Abstract Two novel spectrophotometric determination procedures based on retention of Allura Red onto Amberlite XAD-1180 and XAD-16 resins for its preconcentration, purification, and separation were developed. Analytical parameters of the methods including pH, eluent type, sample volume, and sample and eluent flow rates, were investigated and optimized. Interference effects of some cations, anions, and widely used food dyes were also investigated. Detection limits of the two methods were found to be 1.2 and 1.5 μg/L for XAD-1180 and XAD-16 columns, respectively, under optimum conditions. Linear calibration curve ranges of the methods were 0.4–8.0 and 0.5–6.0 μg/mL of Allura Red for XAD-1180 and XAD-16 resins, respectively. Preconcentration factors were found as 80 for both the XAD-1180 and XAD-16 columns using maximum sample volume and minimum eluent volume. RSDs of the methods were below 6% throughout all experiments. All absorbance measurements were performed at 506 nm. Validations of the methods were performed comparatively with determination of the Allura Red contents of some foodstuff, pharmaceutical, and energy drink samples. Allura Red concentrations in investigated solid and liquid samples ranged from 298 to 501 μg/g and 53.8 to 508 μg/mL, respectively. Satisfactory results were obtained from the real samples analysis. Allura Red contents of samples were determined to be highly similar using the two extraction methods. Comparisons of the methods were performed by analysis of Allura Red contents of the real samples. In addition to analytical parameters, adsorption isotherm studies were performed for the two kinds of Amberlite resins. It was observed that developed methods fit the linear form of the Freundlich adsorption isotherm model. All of the experimental results suggested that the developed SPE procedures are suitable for separation, preconcentration, and determination of Allura Red in solid and liquid matrixes.

In this study, heat transfer and fluid flow characteristics of nonboiling two-phase flow in microchannels were experimentally investigated. The effects of channel diameter (140, 222, 334, and 506 μm) on the Nusselt number and the pressure drop were considered. Air and water were used as the test fluids. Results were presented for the Nusselt number and the pressure drop over a wide range of gas superficial velocity (1.24–40.1 m/s), liquid superficial velocity (0.57–2.13 m/s), and wall heat flux (0.34–0.95 MW/m2). The results showed that the Nusselt number increased with increasing gas flow rate for the large channels of 506 and 334 μm, while the Nusselt number decreased with increasing gas flow for the small channels of 222 and 140 μm. Based on these experimental results, a new correlation for the forced convection Nusselt number was developed. In addition, the two-phase friction multiplier is shown to decrease as channel diameter decreases due to the influence of viscous and surface tension forces.

Bu çalışmada, İlkokula Hazırlık Sürecinde Birlikte Ebeveynlik Ölçeği’nin (İHBEÖ) geliştirilmesi ve geliştirilen ölçeğin geçerlik-güvenirlik gibi psikometrik özellikler açısından incelenmesi amaçlanmıştır. Araştırmanın çalışma grubu, çocuğu ilkokula hazırlık sürecinde bulunan 506 ebeveynden (284 anne, %56.1; 222 baba, %43.9) oluşmaktadır. Araştırma kapsamında geliştirilen ölçeğin, yapı geçerliğini belirlemek için açımlayıcı faktör analizi (AFA) ve doğrulayıcı faktör analizi (DFA) tekniklerinden yararlanılmıştır. Ölçeğin kapsam geçerliği için uzman görüşüne başvurulmuş; ölçüt geçerliği için ise, alanyazında var olan başka bir ölçek ile elde edilen toplam puanlar arasındaki korelasyon değeri hesaplanmıştır. İki farklı örneklem üzerinden gerçekleştirilen analizlerde ilk olarak AFA ile İHBEÖ’nün anlaşma (5 madde), çatışma (5 madde) ve iş bölümü (5 madde) olmak üzere 15 madde ve üç alt boyuttan oluşan ölçek yapısı ortaya çıkarılmış ve ikinci örneklem üzerinden yapılan DFA’da üç faktörlü ölçek yapısının doğrulandığı görülmüştür. Araştırma kapsamında geliştirilen ölçeğin güvenirlik düzeyini belirlemek amacıyla, bütün ölçek formu ve her alt boyut için ayrı ayrı Cronbach Alpha değeri hesaplanmıştır. Yapılan analizler sonucunda, Cronbach Alpha değerinin İHBEÖ’nün alt boyutları için .80 ile .90 arasında değiştiği ve bu değerin toplam ölçek için ise .90 olduğu tespit edilmiştir. Ayrıca ölçek ve alt boyutlarından elde edilen puanların kararlılık düzeyini belirlemek amacıyla test tekrar test yöntemi kullanılmıştır. Araştırma sonuçları, İHBEÖ’nün Türk kültüründe, çocuğu ilkokula hazırlık sürecinde olan ebeveynlerin birlikte ebeveynlik ilişkilerini ölçmek için geçerli, güvenilir ve kullanışlı bir ölçme aracı olduğunu göstermiştir.

Abstract Background and purpose: Therapeutic drug monitoring is a valuable tool supporting immunosuppressive therapy. Significant variation of immunosuppressive drug (ISD) concentrations during their use at similar doses is the basis of dose-normalization strategy. The strategy of dose-adjustment is proposed to identify variability in the rate of ISD metabolism. While the parent drug-to-metabolite ratio (metabolic ratio, MR) represents the rate of formation of individual metabolites. The present study was aimed at evaluation of associations between ISDs’ metabolism rate expressed as dose-adjusted concentrations (C/D) and dose/kg-adjusted concentrations (C/D/kg) and MRs of individual metabolites of tacrolimus, cyclosporine A and MPA precursors. Experimental approach: 506 patients have participated: 284 males (56.13%) and 222 females (43.87%); 318 after kidney (62.85%) and 188 after liver transplantation; median age was 51.34 (39.32-59.95) years and median time after transplantation 78.92 (33.87-138.4) months. Key results: Generally, we have not observed significant relationships between dose-adjusted and dose/kg-adjusted concentrations and MRs of cyclosporine and tacrolimus. Significant correlations were found for: AM9/CsA and dMC-CsA/CsA in kidney transplant recipients and MIII/Tac, AM1/CsA and AM4N/CsA in liver transplant recipients. In contrast, MRs of mycophenolic acid (MPA) metabolites correlated significantly with MPA C/D and C/D/kg both in kidney and liver transplant recipients. Conclusion and implications: In conclusion, easily available and easy to use in clinical practice C/D and C/D/kg ratios cannot be considered as parameters directly reflecting the rate of generation of major metabolites of cyclosporine and tacrolimus both in liver and kidney transplant recipients.

Abstract Background Over the past few decades, neuroimaging research in Bipolar Disorder (BD) has identified neural differences underlying cognitive and emotional processing. However, substantial clinical and methodological heterogeneity present across neuroimaging experiments potentially hinders the identification of consistent neural biomarkers of BD. This meta-analysis aims to comprehensively reassess brain activation and connectivity in BD in order to identify replicable differences that converge across and within resting-state, cognitive, and emotional neuroimaging experiments. Methods Neuroimaging experiments (using fMRI, PET, or arterial spin labeling) reporting whole-brain results in adults with BD and controls published from December 1999—June 18, 2019 were identified via PubMed search. Coordinates showing significant activation and/or connectivity differences between BD participants and controls during resting-state, emotional, or cognitive tasks were extracted. Four parallel, independent meta-analyses were calculated using the revised activation likelihood estimation algorithm: all experiment types, all resting-state experiments, all cognitive experiments, and all emotional experiments. To confirm reliability of identified clusters, two different meta-analytic significance tests were employed. Results 205 published studies yielding 506 individual neuroimaging experiments (150 resting-state, 134 cognitive, 222 emotional) comprising 5745 BD and 8023 control participants were included. Five regions survived both significance tests. Individuals with BD showed functional differences in the right posterior cingulate cortex during resting-state experiments, the left amygdala during emotional experiments, including those using a mixed (positive/negative) valence manipulation, and the left superior and right inferior parietal lobules during cognitive experiments, while hyperactivating the left medial orbitofrontal cortex during cognitive experiments. Across all experiments, there was convergence in the right caudate extending to the ventral striatum, surviving only one significance test. Conclusions Our findings indicate reproducible localization of prefrontal, parietal, and limbic differences distinguishing BD from control participants that are condition-dependent, despite heterogeneity, and point towards a framework for identifying reproducible differences in BD that may guide diagnosis and treatment.

Abstract Background Combined positron emission tomography and computed tomography (PET-CT) using 18F-sodium fluoride (18F-NaF) to detect microcalcification provides the opportunity to gain important insights into disease activity in coronary atherosclerosis. However, the relationship between 18F-NaF uptake and progression of coronary calcification has not been determined. Purpose To determine the relationship between 18F-NaF uptake and progression of coronary calcification in patients with clinically stable coronary artery disease (CAD). Methods Patients with established, multivessel CAD underwent 18F-NaF PET-CT and CT coronary calcium scoring at baseline, with repeat CT calcium scoring at one year. Coronary arterial PET uptake was analysed qualitatively and semi-quantitatively in diseased vessels by measuring maximum tissue-to-background ratio (TBRmax) – defined as the maximum standardised uptake value in a plaque divided by mean blood pool activity measured in the right atrium. Coronary calcification was quantified by measuring calcium mass, volume, average calcium density and total Agatston score (AU). Results In total, 185 patients underwent baseline and repeat imaging (median age 66 years, 80% men), and 118 (64%) had increased 18F-NaF uptake in at least one vessel. Median total calcium score, volume, mass and average density were higher in patients with compared to those without increased 18F-NaF uptake (Table 1). At one year, patients with evidence of increased 18F-NaF uptake demonstrated more rapid progression of coronary calcification (97 [39–166] AU) versus those without uptake (35 [7–93] AU; p<0.0001). Amongst 18F-NaF-positive patients, the calcium score increased only in coronary segments with 18F-NaF uptake (baseline 90.5 [27.5–202] AU versus one year 135.5 [59.3–281.8] AU; p<0.0001) and not in 18F-NaF-negative segments (baseline 44.5 [16–110.5] AU versus one year 46.5 [18.25–114] AU; p=0.446). There was a moderate correlation between TBRmax and change in total calcium score, volume and mass at 1 year (Spearman's Rho = 0.37, 0.38, 0.46 respectively; p<0.0001 for all). Coronary calcification at baseline in PET-negative and PET-positive patients All patients (n=185) 18F-NaF Positive (n=118) 18F-NaF Negative (n=67) P value Agatston Score (AU) 381 [107–892] 541 [245–1130] 136 [55–361] p<0.0001 Calcium Volume (mm3) 358 [131–787] 506 [251–1014] 131 [64–343] p<0.0001 Calcium Mass (mg) 71 [23–155] 100 [48–222] 24 [11–69] p<0.0001 Average Density (mg/mm3) 0.19 [0.17–0.22] 0.20 [0.18–0.23] 0.18 [0.16–0.20] p<0.0001 Conclusions Coronary 18F-NaF uptake identifies both patients and individual coronary segments with greater disease and more rapid progression of coronary calcification over one year. Acknowledgement/Funding AstraZeneca (unrestricted educational grant). British Heart Foundation (CH/09/002, RE/13/3/30183, FS/17/79/33226) Wellcome Trust (WT103782AIA).

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(Benjamin Müsegades, Heidelberg) Berndt, Rainer SJ (Hrsg.), Der Papst und das Buch im Spätmittelalter (1350 – 1500). Bildungsvoraussetzung, Handschriftenherstellung, Bibliotheksgebrauch (Erudiri Sapientia, 13), Münster 2018, Aschendorff, 661 S. / Abb., € 79,00. (Vanina Kopp, Trier) Eßer, Florian, Schisma als Deutungskonflikt. Das Konzil von Pisa und die Lösung des Großen Abendländischen Schismas (1378 – 1409) (Papsttum im mittelalterlichen Europa, 8), Wien / Köln / Weimar 2019, Böhlau, 874 S., € 120,00. (Bernward Schmidt, Eichstätt) Baur, Kilian, Freunde und Feinde. Niederdeutsche, Dänen und die Hanse im Spätmittelalter (1376 – 1513) (Quellen und Darstellungen zur Hansischen Geschichte. Neue Folge, 76), Wien / Köln / Weimar 2018, Böhlau, 671 S., € 85,00. (Angela Huang, Lübeck) Pietsch, Tobias, Führende Gruppierungen im spätmittelalterlichen Niederadel Mecklenburgs, Kiel 2019, Solivagus-Verlag, 459 S. / graph. Darst., € 58,00. (Joachim Krüger, Greifswald) Putzer, Katja, Das Urbarbuch des Erhard Rainer zu Schambach von 1376. Besitz und Bücher eines bayerischen Niederadligen (Quellen und Erörterungen zur bayerischen Geschichte. Neue Folge, 50), München 2019, Beck, 318 S., € 56,00. (Wolfgang Wüst, Erlangen) Drossbach, Gisela / Klaus Wolf (Hrsg.), Reformen vor der Reformation. Sankt Ulrich und Afra und der monastisch-urbane Umkreis im 15. Jahrhundert (Studia Augustana, 18), Berlin / Boston 2018, VII u. 391 S. / Abb., € 99,95. (Thomas Groll, Augsburg) Ricci, Giovanni, Appeal to the Turk. The Broken Boundaries of the Renaissance, übers. v. Richard Chapman (Viella History, Art and Humanities Collection, 4), Rom 2018, Viella, 186 S. / Abb., € 30,00. (Stefan Hanß, Manchester) Böttcher, Hans-Joachim, Die Türkenkriege im Spiegel sächsischer Biographien (Studien zur Geschichte Ungarns, 20), Herne 2019, Schäfer, 290 S., € 19,95. (Fabian Schulze, Elchingen / Augsburg) Shaw, Christine, Isabella d’Este. A Renaissance Princess (Routledge Historical Biographies), London / New York 2019, Routledge, 312 S., £ 90,00. (Christina Antenhofer, Salzburg) Brandtzæg, Siv G. / Paul Goring / Christine Watson (Hrsg.), Travelling Chronicles. News and Newspapers from the Early Modern Period to the Eighteenth Century (Library of the Written Word, 66 / The Handpress World, 51), Leiden / Boston 2018, Brill, XIX u. 388 S. / Abb., € 129,00. (Andreas Würgler, Genf) Graheli, Shanti (Hrsg.), Buying and Selling. The Business of Books in Early Modern Europe (Library of the Written Word, 72; The Handpress World, 55), Leiden / Boston 2019, Brill, XXIII u. 559 S. / Abb., € 159,00. (Johannes Frimmel, München) Vries, Jan de, The Price of Bread. Regulating the Market in the Dutch Republic (Cambridge Studies in Economic History), Cambridge [u. a.] 2019, Cambridge University Press, XIX u. 515 S. / graph. Darst., £ 34,99. (Justus Nipperdey, Saarbrücken) Caesar, Mathieu (Hrsg.), Factional Struggles. Divided Elites in European Cities and Courts (1400 – 1750) (Rulers and Elites, 10), Leiden / Boston 2017, Brill, XI u. 258 S., € 119,00. (Mathis Leibetseder, Berlin) Freytag, Christine / Sascha Salatowsky (Hrsg.), Frühneuzeitliche Bildungssysteme im interkonfessionellen Vergleich. Inhalte – Infrastrukturen – Praktiken (Gothaer Forschungen zur Frühen Neuzeit, 14), Stuttgart 2019, Steiner, 320 S., € 58,00. (Helmut Puff, Ann Arbor) Amend-Traut, Anja / Josef Bongartz / Alexander Denzler / Ellen Franke / Stefan A. Stodolkowitz (Hrsg.), Unter der Linde und vor dem Kaiser. Neue Perspektiven auf Gerichtsvielfalt und Gerichtslandschaften im Heiligen Römischen Reich (Quellen und Forschungen zur höchsten Gerichtsbarkeit im Alten Reich, 73), Wien / Köln / Weimar 2020, Böhlau, 320 S., € 65,00. (Tobias Schenk, Wien) Rittgers, Ronald K. / Vincent Evener (Hrsg.), Protestants and Mysticism in Reformation Europe (St Andrews Studies in Reformation History), Leiden / Boston 2019, Brill, XIV u. 459 S., € 156,00. (Lennart Gard, Berlin) Temple, Liam P., Mysticism in Early Modern England (Studies in Modern British Religious History, 38), Woodbridge 2019, The Boydell Press, IX u. 221 S. / Abb., £ 60,00. (Elisabeth Fischer, Hamburg) Kroll, Frank-Lothar / Glyn Redworth / Dieter J. Weiß (Hrsg.), Deutschland und die Britischen Inseln im Reformationsgeschehen. Vergleich, Transfer, Verflechtungen (Prinz-Albert-Studien, 34; Arbeiten zur Kirchengeschichte Bayerns, 97), Berlin 2018, Duncker &amp; Humblot, X u. 350 S., € 79,90. (Andreas Pečar, Halle a. d. S.) Breul, Wolfgang / Kurt Andermann (Hrsg.), Ritterschaft und Reformation (Geschichtliche Landeskunde, 75), Stuttgart 2019, Steiner, 374 S., € 63,00. (Andreas Flurschütz da Cruz, Bamberg) Niederhäuser, Peter / Regula Schmid (Hrsg.), Querblicke. Zürcher Reformationsgeschichten (Mitteilungen der Antiquarischen Gesellschaft in Zürich, 86), Zürich 2019, Chronos, 203 S. / Abb., € 48,00. (Volker Reinhardt, Fribourg) Braun, Karl-Heinz / Wilbirgis Klaiber / Christoph Moos (Hrsg.), Glaube‍(n) im Disput. Neuere Forschungen zu den altgläubigen Kontroversisten des Reformationszeitalters (Reformationsgeschichtliche Studien und Texte, 173), Münster 2020, Aschendorff, IX u. 404 S., € 68,00. (Volker Leppin, Tübingen) Fata, Márta / András Forgó / Gabriele Haug-Moritz / Anton Schindling (Hrsg.), Das Trienter Konzil und seine Rezeption im Ungarn des 16. und 17. Jahrhunderts (Reformationsgeschichtliche Studien und Texte, 171), Münster 2019, VI u. 301 S., € 46,00. (Joachim Werz, Frankfurt a. M.) Tol, Jonas van, Germany and the French Wars of Religion, 1560 – 1572 (St Andrews Studies in Reformation History), Leiden / Boston 2019, Brill, VIII u. 274 S. / Abb., € 125,00. (Alexandra Schäfer-Griebel, Mainz) Lipscomb, Suzannah, The Voices of Nîmes. Women, Sex, and Marriage in Reformation Languedoc, Oxford / New York 2019, Oxford University Press, XIV u. 378 S., £ 30,00. (Adrina Schulz, Zürich) Kielinger, Thomas, Die Königin. Elisabeth I. und der Kampf um England. Biographie, München 2019, Beck, 375 S. / Abb., € 24,95. (Pauline Puppel, Aumühle) Canning, Ruth, The Old English in Early Modern Ireland. The Palesmen and the Nine Years’ War, 1594 – 1603 (Irish Historical Monograph Series, [20]), Woodbridge 2019, The Boydell Press, XI u. 227 S., £ 75,00. (Martin Foerster, Düsseldorf) Bry, Theodor de, America. Sämtliche Tafeln 1590 – 1602, hrsg. v. Michiel van Groesen / Larry E. Tise, Köln 2019, Taschen, 375 S. / Abb., € 100,00. (Renate Dürr, Tübingen) Haskell, Yasmin / Raphaële Garrod (Hrsg.), Changing Hearts. Performing Jesuit Emotions between Europe, Asia, and the Americas (Jesuit Studies, 15), Leiden / Boston 2019, Brill, XIX u. 328 S. / Abb., € 130,00. (Christoph Nebgen, Saarbrücken) Jackson, Robert H., Regional Conflict and Demographic Patterns on the Jesuit Missions among the Guaraní in the Seventeenth and Eighteenth Centuries (European Expansion and Indigenous Response, 31), Leiden / Boston 2019, Brill, XVII u. 174 S. / Abb., € 100,00. (Irina Saladin, Tübingen) Kelly, James / Hannah Thomas (Hrsg.), Jesuit Intellectual and Physical Exchange between England and Mainland Europe, c. 1580 – 1789: „The world is our house“? (Jesuit Studies, 18), Leiden / Boston 2019, Brill, XIV u. 371 S., € 140,00. (Martin Foerster, Hamburg) Wilhelm, Andreas, Orange und das Haus Nassau-Oranien im 17. Jahrhundert. Ein Fürstentum zwischen Souveränität und Abhängigkeit, Berlin [u. a.] 2018, Lang, 198 S., € 39,95. (Olaf Mörke, Kiel) Geraerts, Jaap, Patrons of the Old Faith. The Catholic Nobility in Utrecht and Guelders, c. 1580 – 1702 (Catholic Christendom, 1300 – 1700), Leiden / Boston 2019, Brill, XIII, 325 S. / Abb., € 129,00. (Johannes Arndt, Münster) Arnegger, Katharina, Das Fürstentum Liechtenstein. Session und Votum im Reichsfürstenrat, Münster 2019, Aschendorff, 256 S., € 24,80. (Tobias Schenk, Wien) Marti, Hanspeter / Robert Seidel (Hrsg.), Die Universität Straßburg zwischen Späthumanismus und Französischer Revolution, Wien / Köln / Weimar 2018, Böhlau, VII u. 549 S. / Abb., € 80,00. (Wolfgang E. J. Weber, Augsburg) Kling, Alexander, Unter Wölfen. Geschichten der Zivilisation und der Souveränität vom 30-jährigen Krieg bis zur Französischen Revolution (Rombach Wissenschaft. Reihe Cultural Animal Studies, 2), Freiburg i. Br. / Berlin / Wien 2019, Rombach, 581 S., € 68,00. (Norbert Schindler, Salzburg) Arnke, Volker, „Vom Frieden“ im Dreißigjährigen Krieg. Nicolaus Schaffshausens „De Pace“ und der positive Frieden in der Politiktheorie (Bibliothek Altes Reich, 25), Berlin / Boston 2018, de Gruyter Oldenbourg, IX u. 294 S., € 89,95. (Fabian Schulze, Elchingen / Augsburg) Zirr, Alexander, Die Schweden in Leipzig. Die Besetzung der Stadt im Dreißigjährigen Krieg (1642 – 1650) (Quellen und Forschungen zur Geschichte der Stadt Leipzig, 14), Leipzig 2018, Leipziger Universitätsverlag, 939 S. / Abb., € 98,00. (Philip Hoffmann-Rehnitz, Münster) Fehler, Timothy G. / Abigail J. Hartman (Hrsg.), Signs and Wonders in Britain’s Age of Revolution. A Sourcebook, London / New York 2019, Routledge, XVII u. 312 S. / Abb., £ 110,00. (Doris Gruber, Wien) Dorna, Maciej, Mabillon und andere. Die Anfänge der Diplomatik, aus dem Polnischen übers. v. Martin Faber (Wolfenbütteler Forschungen, 159), Wiesbaden 2019, Harrassowitz in Kommission, 287 S. / Abb., € 49,00. (Wolfgang Eric Wagner, Münster) Kramper, Peter, The Battle of the Standards. Messen, Zählen und Wiegen in Westeuropa 1660 – 1914 (Veröffentlichungen des Deutschen Historischen Instituts London / Publications of the German Historical Institute London / Publications of the German Historical Institute, 82), Berlin / Boston 2019, de Gruyter Oldenbourg, X u. 599 S., € 69,95. (Miloš Vec, Wien) Schilling, Lothar / Jakob Vogel (Hrsg.), Transnational Cultures of Expertise. Circulating State-Related Knowledge in the 18th and 19th Centuries (Colloquia Augustana, 36), Berlin / Boston 2019, de Gruyter Oldenbourg, X u. 201 S., € 59,95. (Justus Nipperdey, Saarbrücken) Carhart, Michael C., Leibniz Discovers Asia. Social Networking in the Republic of Letters, Baltimore 2019, Johns Hopkins University Press, XVI u. 324 S. / Abb., $ 64,95. (Markus Friedrich, Hamburg) Wolf, Hubert, Verdammtes Licht. Der Katholizismus und die Aufklärung, München 2019, Beck, 314 S., € 29,95. (Wolfgang Reinhard, Freiburg i. Br.) Holenstein, André / Claire Jaquier / Timothée Léchot / Daniel Schläppi (Hrsg.), Politische, gelehrte und imaginierte Schweiz. Kohäsion und Disparität im Corpus helveticum des 18. Jahrhunderts / Suisse politique, savante et imaginaire. Cohésion et disparité du Corps helvétique au XVIIIe siècle (Travaux sur la Suisse des Lumières, 20), Genf 2019, Éditions Slatkine, 386 S. / Abb., € 40,00. (Lisa Kolb, Augsburg) Williams, Samantha, Unmarried Motherhood in the Metropolis, 1700 – 1850. Pregnancy, the Poor Law and Provisions, Cham 2018, Palgrave Macmillan, XV u. 270 S. / graph. Darst., € 96,29. (Annette C. Cremer, Gießen) Wirkner, Christian, Logenleben. Göttinger Freimaurerei im 18. Jahrhundert (Ancien Régime, Aufklärung und Revolution, 45), Berlin / Boston 2019, de Gruyter Oldenbourg, VIII u. 632 S. / Abb., € 89,95. (Helmut Reinalter, Innsbruck) Göse, Frank, Friedrich Wilhelm I. Die vielen Gesichter des Soldatenkönigs, Darmstadt 2020, wbg Theiss, 604 S. / Abb., € 38,00. (Michael Kaiser, Bonn) Querengässer, Alexander, Das kursächsische Militär im Großen Nordischen Krieg 1700 – 1717 (Krieg in der Geschichte, 107), Berlin 2019, Duncker &amp; Humblot, 628 S. / graph. Darst., € 148,00. (Tilman Stieve, Aachen) Sirota, Brent S. / Allan I. Macinnes (Hrsg.), The Hanoverian Succession in Great Britain and Its Empire (Studies in Early Modern Cultural, Political and Social History, 35), Woodbridge 2019, The Boydell Press, IX u. 222 S. / graph. Darst., £ 65,00. (Georg Eckert, Wuppertal / Potsdam) Petersen, Sven, Die belagerte Stadt. Alltag und Gewalt im Österreichischen Erbfolgekrieg (1740 – 1748) (Krieg und Konflikt, 6), Frankfurt a. M. / New York 2019, Campus, 487 S., € 45,00. (Bernhard R. Kroener, Freiburg i. Br.) Lounissi, Carine, Thomas Paine and the French Revolution, Cham 2018, Palgrave Macmillan, IX u. 321 S., € 96,29. (Volker Depkat, Regensburg) Kern, Florian, Kriegsgefangenschaft im Zeitalter Napoleons. Über Leben und Sterben im Krieg (Konsulat und Kaiserreich, 5), Berlin [u. a.] 2018, Lang, 352 S., € 71,95. (Jürgen Luh, Potsdam)