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Reasons for optimism for each MLB club

On this opening week of Spring Training, all 30 Major League teams have one thing in common: optimism. Here's an optimism cheat sheet for each of them.




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Vitamin C in Human Health and Disease: Effects, Mechanisms of Action, and New Guidance on Intake




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Myocardial Blood Flow and Myocardial Flow Reserve After Cardiac Transplantation: Mistakes in Diagnostic Value and Prognosis




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Human Radiation Dosimetry for Orally and Intravenously Administered 18F-FDG

Intravenous access is difficult in some patients referred for 18F-FDG PET imaging. Extravasation at the injection site and accumulation in central catheters can lead to limited tumor 18F-FDG uptake, erroneous quantitation, and significant image artifacts. In this study, we compared the human biodistribution and dosimetry for 18F-FDG after oral and intravenous administrations sequentially in the same subjects to ascertain the dosimetry and potential suitability of orally administered 18F-FDG as an alternative to intravenous administration. We also compared our detailed intravenous 18F-FDG dosimetry with older dosimetry data. Methods: Nine healthy volunteers (6 male and 3 female; aged 19–32 y) underwent PET/CT imaging after oral and intravenous administration of 18F-FDG. Identical preparation and imaging protocols (except administration route) were used for oral and intravenous studies. During each imaging session, 9 whole-body PET scans were obtained at 5, 10, 20, 30, 40, 50, 60, 120, and 240 min after 18F-FDG administration (370 ± 16 MBq). Source organ contours drawn using CT were overlaid onto registered PET images to extract time–activity curves. Time-integrated activity coefficients derived from time–activity curves were given as input to OLINDA/EXM for dose calculations. Results: Blood uptake after orally administered 18F-FDG peaked at 45–50 min after ingestion. The oral-to-intravenous ratios of 18F-FDG uptake for major organs at 45 min were 1.07 ± 0.24 for blood, 0.94 ± 0.39 for heart wall, 0.47 ± 0.12 for brain, 1.25 ± 0.18 for liver, and 0.84 ± 0.24 for kidneys. The highest organ-absorbed doses (μGy/MBq) after oral 18F-FDG administration were observed for urinary bladder (75.9 ± 17.2), stomach (48.4 ± 14.3), and brain (29.4 ± 5.1), and the effective dose was significantly higher (20%) than after intravenous administration (P = 0.002). Conclusion: 18F-FDG has excellent bioavailability after oral administration, but peak organ activities occur later than after intravenous injection. These data suggest PET at 2 h after oral 18F-FDG administration should yield images that are comparable in biodistribution to conventional clinical images acquired 1 h after injection. Oral 18F-FDG is a palatable alternative to intravenous 18F-FDG when venous access is problematic.




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Preoperative Localization of Adenomas in Primary Hyperparathyroidism: The Value of 11C-Choline PET/CT in Patients with Negative or Discordant Findings on Ultrasonography and 99mTc-Sestamibi SPECT/CT

We aimed to assess the value of 11C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on 99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUVmax and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the 11C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUVmax was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that 11C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and 99mTc-sestamibi imaging yield negative or discordant results.




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18F-Fluorocholine PET/CT in Primary Hyperparathyroidism: Superior Diagnostic Performance to Conventional Scintigraphic Imaging for Localization of Hyperfunctioning Parathyroid Glands

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging 18F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with 18F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of 99mTc-sestamibi SPECT/CT, 99mTc-sestamibi/pertechnetate subtraction imaging, and 99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of 18F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%–56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%–34% (44% combined). Conclusion: 18F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.




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Prospective Evaluation of 18F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer in an Academic Center: A Focus on Disease Localization and Changes in Management

18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52–91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), 18F-fluciclovine PET/CT (18), or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results: 18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA < 0.5), 69% (0.5 ≤ PSA < 1), 100% (1 ≤ PSA < 2), 91% (2 ≤ PSA < 5), and 96% (PSA ≥ 5). 18F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20 of 41 (49%) CT or MRI scans had findings congruent with 18F-DCFPyL, whereas 18F-DCFPyL PET was positive in 17 of 41 (41%) cases with negative CT or MRI findings. For bone imaging, 26 of 38 (68%) bone or 18F-NaF PET scans were congruent with 18F-DCFPyL PET, whereas 18F-DCFPyL PET localized bone lesions in 8 of 38 (21%) patients with negative results on bone or 18F-NaF PET scans. In 8 of 18 (44%) patients, 18F-fluciclovine PET had located the same lesions as did 18F-DCFPyL PET, whereas 5 of 18 (28%) patients with negative 18F-fluciclovine findings had positive 18F-DCFPyL PET findings and 1 of 18 (6%) patients with negative 18F-DCFPyL findings had uptake in the prostate bed on 18F-fluciclovine PET. In the remaining 4 of 18 (22%) patients, 18F-DCFPyL and 18F-fluciclovine scans showed different lesions. Lastly, 43 of 72 (60%) patients had treatment changes after 18F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18F-DCFPyL PET, despite negative results on conventional imaging. Conclusion: 18F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent PC, given the high positivity rate as compared with Food and Drug Administration–approved currently available imaging modalities and its impact on clinical management in 60% of patients.




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Comparison of 3 Interpretation Criteria for 68Ga-PSMA11 PET Based on Inter- and Intrareader Agreement

PET using radiolabeled prostate-specific membrane antigen (PSMA) is now being more widely adopted as a valuable tool to evaluate patients with prostate cancer (PC). Recently, 3 different criteria for interpretation of PSMA PET were published: the European Association of Nuclear Medicine (EANM) criteria, the Prostate Cancer Molecular Imaging Standardized Evaluation criteria, and the PSMA Reporting and Data System. We compared these 3 criteria in terms of interreader, intrareader, and intercriteria agreement. Methods: Data from 104 patients prospectively enrolled in research protocols at our institution were retrospectively reviewed. The cohort consisted of 2 groups: 47 patients (mean age, 64.2 y old) who underwent Glu-NH-CO-NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA11) PET/MRI for initial staging of biopsy-proven intermediate- or high-risk PC, and 57 patients (mean age, 70.5 y old) who underwent 68Ga-PSMA11 PET/CT because of biochemically recurrent PC. Three nuclear medicine physicians independently evaluated all 68Ga-PSMA11 PET/MRI and PET/CT studies according to the 3 interpretation criteria. Two of them reevaluated all studies 6 mo later in the same manner and masked to the initial reading. The Gwet agreement coefficient was calculated to evaluate interreader, intrareader, and intercriteria agreement based on the following sites: local lesion (primary tumor or prostate bed after radical prostatectomy), lymph node metastases, and other metastases. Results: In the PET/MRI group, interreader, intrareader, and intercriteria agreement ranged from substantial to almost perfect for any site according to all 3 criteria. In the PET/CT group, interreader agreement ranged from substantial to almost perfect except for judgment of distant metastases based on the PSMA Reporting and Data System (Gwet agreement coefficient, 0.57; moderate agreement), in which the most frequent cause of disagreement was lung nodules. Intrareader agreement ranged from substantial to almost perfect for any site according to all 3 criteria. Intercriteria agreement for each site was also substantial to almost perfect. Conclusion: Although the 3 published criteria have good interreader and intrareader reproducibility in evaluating 68Ga-PSMA11 PET, there are some factors causing interreader disagreement. Further work is needed to address this issue.




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Head-to-Head Comparison of 68Ga-PSMA-11 with 18F-PSMA-1007 PET/CT in Staging Prostate Cancer Using Histopathology and Immunohistochemical Analysis as a Reference Standard

18F-PSMA-1007 is a novel prostate-specific membrane antigen (PSMA)–based radiopharmaceutical for imaging prostate cancer (PCa). The aim of this study was to compare the diagnostic accuracy of 18F-PSMA-1007 with 68Ga-PSMA-11 PET/CT in the same patients presenting with newly diagnosed intermediate- or high-risk PCa. Methods: Sixteen patients with intermediate- or high-risk PCa underwent 18F-PSMA-1007 and 68Ga-PSMA-11 PET/CT within 15 d. PET findings were compared between the 2 radiotracers and with reference-standard pathologic specimens obtained from radical prostatectomy. The Cohen -coefficient was used to assess the concordance between 18F-PSMA-1007 and 68Ga-PSMA-11 for detection of intraprostatic lesions. The McNemar test was used to assess agreement between intraprostatic PET/CT findings and histopathologic findings. Sensitivity, specificity, positive predictive value, and negative predictive value were reported for each radiotracer. SUVmax was measured for all lesions, and tumor-to-background activity was calculated. Areas under receiver-operating-characteristic curves were calculated for discriminating diseased from nondiseased prostate segments, and optimal SUV cutoffs were calculated using the Youden index for each radiotracer. Results: PSMA-avid lesions in the prostate were identified in all 16 patients with an almost perfect concordance between the 2 tracers ( ranged from 0.871 to 1). Aside from the dominant intraprostatic lesion, similarly detected by both radiotracers, a second less intense positive focus was detected in 4 patients only with 18F-PSMA-1007. Three of these secondary foci were confirmed as Gleason grade 3 lesions, whereas the fourth was shown on pathologic examination to represent chronic prostatitis. Conclusion: This pilot study showed that both 18F-PSMA-1007 and 68Ga-PSMA-11 identify all dominant prostatic lesions in patients with intermediate- or high-risk PCa at staging. 18F-PSMA-1007, however, may detect additional low-grade lesions of limited clinical relevance.




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Cholecystokinin 2 Receptor Agonist 177Lu-PP-F11N for Radionuclide Therapy of Medullary Thyroid Carcinoma: Results of the Lumed Phase 0a Study

Treatment of patients with advanced medullary thyroid carcinoma (MTC) is still a challenge. For more than 2 decades, it has been known that the cholecystokinin 2 receptor is a promising target for the treatment of MTC with radiolabeled minigastrin analogs. Unfortunately, kidney toxicity has precluded their therapeutic application so far. In 6 consecutive patients, we evaluated with advanced 3-dimensional dosimetry whether improved minigastrin analog 177Lu-DOTA-(d-Glu)6-Ala-Tyr-Gly-Trp-Nle-Asp-PheNH2 (177Lu-PP-F11N) is a suitable agent for the treatment of MTC. Methods: Patients received 2 injections of about 1 GBq (~80 μg) of 177Lu-PP-F11N with and without a solution of succinylated gelatin (SG, a plasma expander used for nephroprotection) in a random crossover sequence to evaluate biodistribution, pharmacokinetics, and tumor and organ dosimetry. An electrocardiogram was obtained and blood count and blood chemistry were measured up to 12 wk after the administration of 177Lu-PP-F11N to assess safety. Results: In all patients, 177Lu-PP-F11N accumulation was visible in tumor tissue, stomach, and kidneys. Altogether, 13 tumors were eligible for dosimetry. The median absorbed doses for tumors, stomach, kidneys, and bone marrow were 0.88 (interquartile range [IQR]: 0.85–1.04), 0.42 (IQR: 0.25–1.01), 0.11 (IQR: 0.07–0.13), and 0.028 (IQR: 0.026–0.034) Gy/GBq, respectively. These doses resulted in median tumor-to-kidney dose ratios of 11.6 (IQR: 8.11–14.4) without SG and 13.0 (IQR: 10.2–18.6) with SG; these values were not significantly different (P = 1.0). The median tumor-to-stomach dose ratio was 3.34 (IQR: 1.14–4.70). Adverse reactions (mainly hypotension, flushing, and hypokalemia) were self-limiting and not higher than grade 1. Conclusion: 177Lu-PP-F11N accumulates specifically in MTC at a dose that is sufficient for a therapeutic approach. With a low kidney and bone marrow radiation dose, 177Lu-PP-F11N shows a promising biodistribution. The dose-limiting organ is most likely the stomach. Further clinical studies are necessary to evaluate the maximum tolerated dose and the efficacy of 177Lu-PP-F11N.




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First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of 89Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: 89Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most 89Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.




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Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%–92%) and 84% (95% confidence interval, 69%–93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%–95%) and specificity of 85% (95% confidence interval, 71%–93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%–98%) and specificity was 82% (95% confidence interval, 68%–91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%–100% and 0%–100%, respectively, for 18F-FLT; 85%–100% and 72%–100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%–88%, respectively, for 11C-choline. Conclusion: 18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.




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Congressional Briefing: Diagnostic Imaging and Alzheimer Disease




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SNMMI at NRC Commissioners Meeting




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This Month in JNM




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Fibrotic Encapsulation Is the Dominant Source of Continuous Glucose Monitor Delays

Continuous glucose monitor (CGM) readings are delayed relative to blood glucose, and this delay is usually attributed to the latency of interstitial glucose levels. However, CGM-independent data suggest rapid equilibration of interstitial glucose. This study sought to determine the loci of CGM delays. Electrical current was measured directly from CGM electrodes to define sensor kinetics in the absence of smoothing algorithms. CGMs were implanted in mice, and sensor versus blood glucose responses were measured after an intravenous glucose challenge. Dispersion of a fluorescent glucose analog (2-NBDG) into the CGM microenvironment was observed in vivo using intravital microscopy. Tissue deposited on the sensor and nonimplanted subcutaneous adipose tissue was then collected for histological analysis. The time to half-maximum CGM response in vitro was 35 ± 2 s. In vivo, CGMs took 24 ± 7 min to reach maximum current versus 2 ± 1 min to maximum blood glucose (P = 0.0017). 2-NBDG took 21 ± 7 min to reach maximum fluorescence at the sensor versus 6 ± 6 min in adipose tissue (P = 0.0011). Collagen content was closely correlated with 2-NBDG latency (R = 0.96, P = 0.0004). Diffusion of glucose into the tissue deposited on a CGM is substantially delayed relative to interstitial fluid. A CGM that resists fibrous encapsulation would better approximate real-time deviations in blood glucose.




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Immunomodulation Followed by Antigen-Specific Treg Infusion Controls Islet Autoimmunity

Optimal immune-based therapies for type 1 diabetes (T1D) should restore self-tolerance without inducing chronic immunosuppression. CD4+Foxp3+ regulatory T cells (Tregs) are a key cell population capable of facilitating durable immune tolerance. However, clinical trials with expanded Tregs in T1D and solid-organ transplant recipients are limited by poor Treg engraftment without host manipulation. We showed that Treg engraftment and therapeutic benefit in nonautoimmune models required ablative host conditioning. Here, we evaluated Treg engraftment and therapeutic efficacy in the nonobese diabetic (NOD) mouse model of autoimmune diabetes using nonablative, combinatorial regimens involving the anti-CD3 (αCD3), cyclophosphamide (CyP), and IAC (IL-2/JES6–1) antibody complex. We demonstrate that αCD3 alone induced substantial T-cell depletion, impacting both conventional T cells (Tconv) and Tregs, subsequently followed by more rapid rebound of Tregs. Despite robust depletion of host Tconv and host Tregs, donor Tregs failed to engraft even with interleukin-2 (IL-2) support. A single dose of CyP after αCD3 depleted rebounding host Tregs and resulted in a 43-fold increase in donor Treg engraftment, yet polyclonal donor Tregs failed to reverse diabetes. However, infusion of autoantigen-specific Tregs after αCD3 alone resulted in robust Treg engraftment within the islets and induced remission in all mice. This novel combinatorial therapy promotes engraftment of autoantigen-specific donor Tregs and controls islet autoimmunity without long-term immunosuppression.




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Evidence of Tissue Repair in Human Donor Pancreas After Prolonged Duration of Stay in Intensive Care

M2 macrophages play an important role in tissue repair and regeneration. They have also been found to modulate β-cell replication in mouse models of pancreatic injury and disease. We previously reported that β-cell replication is strongly increased in a subgroup of human organ donors characterized by prolonged duration of stay in an intensive care unit (ICU) and increased number of leukocytes in the pancreatic tissue. In the present study we investigated the relationship between duration of stay in the ICU, M2 macrophages, vascularization, and pancreatic cell replication. Pancreatic organs from 50 donors without diabetes with different durations of stay in the ICU were analyzed by immunostaining and digital image analysis. The number of CD68+CD206+ M2 macrophages increased three- to sixfold from ≥6 days’ duration of stay in the ICU onwards. This was accompanied by a threefold increased vascular density and a four- to ninefold increase in pancreatic cells positive for the replication marker Ki67. A strong correlation was observed between the number of M2 macrophages and β-cell replication. These results show that a prolonged duration of stay in the ICU is associated with an increased M2 macrophage number, increased vascular density, and an overall increase in replication of all pancreatic cell types. Our data show evidence of marked levels of tissue repair in the human donor pancreas.




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Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial




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Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study




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Global, regional, and national burden of neck pain in the general population, 1990-2017: systematic analysis of the Global Burden of Disease Study 2017




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Opioid agonist treatment and risk of mortality during opioid overdose public health emergency: population based retrospective cohort study




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Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials




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Infectious diseases in children and adolescents in China: analysis of national surveillance data from 2008 to 2017




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Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal




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Use of electronic medical records in development and validation of risk prediction models of hospital readmission: systematic review




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Association between maternal and paternal mental illness and risk of injuries in children and adolescents: nationwide register based cohort study in Sweden




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Prospective registration and reporting of trial number in randomised clinical trials: global cross sectional study of the adoption of ICMJE and Declaration of Helsinki recommendations




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Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study




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Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution: modelling study




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Term complications and subsequent risk of preterm birth: registry based study




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Use of sodium-glucose co-transporter 2 inhibitors and risk of serious renal events: Scandinavian cohort study




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Occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis




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Association between tax on sugar sweetened beverages and soft drink consumption in adults in Mexico: open cohort longitudinal analysis of Health Workers Cohort Study




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Use of genetic variation to separate the effects of early and later life adiposity on disease risk: mendelian randomisation study




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Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis




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Dwayne Devonish | Smart virus testing necessary for economic reboot

OP-ED CONTRIBUTION: COVID-19 AND THE ECONOMY FOR MOST countries in the Caribbean, the current testing for COVID-19 has not reached levels suitable for ascertaining an accurate picture of the state of outbreak and spread of the infection. This...




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Sagicor raises doubt about Scotia Life T&amp;T deal

Sagicor Finance Company has raised doubt about whether the deal to acquire the assets of Scotia Life Trinidad...




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Vassilis Ntousas

Stavros Niarchos Foundation Academy Fellow, Europe Programme

Biography

Vassilis Ntousas is hosted by the Europe Programme. His research focuses on the links between EU foreign policy in an era of global institutional turbulence and the defence and transformation of the multilateral system.

From 2015-2019, he was the senior international relations policy advisor at the Foundation for European Progressive Studies (FEPS) in Brussels. In this role, he was responsible for leading the design and implementation of the foundation’s global research and activity programmes, covering the world’s major regions.

Prior to FEPS, he worked as a communications and political advisor at the Municipality of Thessaloniki, Greece, providing advice in the areas of international affairs and intercity diplomatic relations.

He regularly comments on international developments for international and Greek media outlets.

Vassilis holds an MSc in International Relations from the London School of Economics and a BA in International Relations and Politics from the University of Sheffield.

Areas of expertise

  • European foreign policy
  • Transatlantic relations
  • The politics and policies of the EU towards the Middle East
  • Iran nuclear agreement

Past experience

2015-19Senior international relations policy advisor, Foundation for European Progressive Studies

2013-14

Political and communications advisor, Municipality of Thessaloniki, Greece

2012

Project assistant, APCO Worldwide, Brussels office




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Can the New European Commission Deliver on Its Promises to Africa?

4 December 2019

Fergus Kell

Projects Assistant, Africa Programme

Damir Kurtagic

Former Academy Robert Bosch Fellow, Africa Programme
Familiar promises of equal partnership must be backed by bolder action, including an expanded budget, internal reform and a rethink of its approach to trade negotiations.

2019-12-03-Urpilainen.jpg

Jutta Urpilainen, new EU commissioner for international partnerships, at the European Parliament in Brussels in October. Photo: Getty Images.

The new European Commission, headed by Ursula von der Leyen, assumed office on 1 December, and there are early signs that Africa will begin near the top of their foreign policy priorities. Policy towards Africa under the new EU administration is yet to be fully defined, but its contours are already visible in the selection of commissioners and assignment of portfolios.  

Although rumours of a dedicated commissioner for Africa were unfounded, the appointment of Jutta Urpilainen to the new role of commissioner for international partnerships – replacing the former post of development commissioner – is a strong signal of ongoing change in EU development thinking, away from bilateral aid towards trade and investment, including by the private sector. 

This may have significant consequences for the EU’s relationship with Africa. In her mission letter to Urpilainen in September, von der Leyen listed the first objective as a new ‘comprehensive strategy for Africa’. Urpilainen, Finland’s finance minister before being posted to Ethiopia as special representative on mediation, has also described her appointment as an opportunity to move on from traditional measures of aid delivery. 

Ambition or incoherence? 

However, this ambition may be at odds with other EU priorities and practices, notably managing migration and institutions and instruments for governing EU–Africa relations that remain rooted in a ‘traditional’ model of North–South development cooperation rather than equitable partnership.

Another newly created post will see Margaritis Schinas assume the role of vice-president for promoting the European way of life – formerly ‘protecting our European way of life’ before a backlash saw it changed – a reminder that migration will remain high on the EU’s foreign policy agenda. The new high representative for foreign and security policy and chief EU diplomat, Josep Borrell, has highlighted the need for bilateral partnership with countries of origin and transit, mainly in Africa. 

Negotiations also continue to stall on a replacement to the Cotonou Agreement, the 20-year partnership framework between the EU and the African, Caribbean and Pacific (ACP) group of states, which now looks certain to be extended for at least 12 months beyond its expiry in February 2020.

Ambiguities in the EU’s negotiating approach have certainly contributed to the delay: having pushed initially for a separate regional pillar for Africa that would be opened to the North African countries (who are not ACP members) and include a loosely defined role for the African Union, this would later be abandoned in favour of a dual-track process on separate new agreements with the AU and ACP respectively.

The EU also continues to pursue controversial economic partnership agreements under the aegis of Cotonou, despite their increasing appearance of incompatibility with the pathbreaking African Continental Free Trade Area (AfCFTA) – one of the clearest expressions to date of African agency.

The EU has so far attempted to gloss over this incoherence, claiming that EPAs can somehow act as the ‘building blocks’ for Africa-wide economic integration. But tensions are appearing between EU departments and within the commission, with the European External Action Service inclined to prioritize a more strategic continental relationship with the AU, while the Directorate-General for International Cooperation and Development remains committed to the ACP as the conduit for financial support and aid delivery.

And it is unlikely to get away with such incoherence for much longer. Change is now urgent, as numerous countries in sub-Saharan Africa continue to attract the strategic and commercial interests of the EU’s competitors: from established players such as China and potentially in future the UK, which is intent on remodelling its Africa ties post-Brexit, to emerging actors such as Turkey or Russia, which held its first Africa summit in October. 

The need for delivery

If the EU is serious about its rhetoric on equal partnership, it must therefore move beyond convoluted hybrid proposals. Delivering on the Juncker administration’s proposal to increase funding for external action by 30 per cent for 2021–27 would mark an important first step, particularly as this involves streamlining that would see the European Development Fund – the financial instrument for EU-ACP relations – incorporated into the main EU budget.

The new commission should therefore continue to exert pressure on the European Council and European Parliament to adopt this proposal, as negotiations on this financial framework have been repeatedly subject to delay and may not be resolved before the end of the year. 

Beyond this, proactive support for the AfCFTA and for structural transformation more broadly must be prioritized ahead of vague promises for a continent-to-continent free trade agreement, as held out by Juncker in his final State of the Union address in 2018. 

The significance of internal EU reforms for Africa should also not be discounted. The EU’s Common Agricultural Policy, for instance, has placed the African sector at a particular disadvantage and has made it harder to compete even in domestic markets, let alone in the distant EU export markets. EU efforts to stimulate inflows of private investments into the African agricultural sector, abolish import tariffs and offer technical support for African producers to satisfy EU health and safety regulations will be of little use if they are undermined by heavy subsidies across Europe.

Ultimately, changes to job titles alone will be insufficient. The new commission’s rhetoric, while ambitious, differs little from that of the previous decade – Africa has heard the promise of a ‘partnership of equals’ and of ‘shared ownership’ since before the advent of the Joint Africa–EU Strategy in 2007. Now is the time for truly bold steps to implement this vision.




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Polish-British Belvedere Forum 2020

Research Event

3 March 2020 - 2:00pm to 4 March 2020 - 3:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

The Belvedere Forum is a leading annual British and Polish bilateral dialogue bringing together a diverse group of actors from civil society, politics, business, academia and NGOs. It seeks to strengthen and deepen the extensive partnership between the two countries by exploring political, economic, social and cultural issues through debate and discussion.

The forum is an annual event alternating between the UK and Poland. Originally created in 2017 by the governments of the UK and Poland, the forum is now jointly organized by Chatham House and the Polish Institute of International Affairs (PISM) in Warsaw.

Anna Dorant-Hayes

Executive Assistant to the Director
+44 (0)20 7957 5702




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POSTPONED: Is a 'Geopolitical' Europe Possible?

Invitation Only Research Event

25 March 2020 - 8:30am to 9:30am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Michael Karnitschnig, Director for External Relations, Secretariat-General, European Commission

What role does the EU want to play in a world characterised increasingly by power politics? The new European Commission has explicitly stated its ambition for the EU to become a stronger geopolitical actor. Is it capable of becoming a third pole in an enduring US-China stand-off?

From climate change to trade policy and security, the next 5 years may prove decisive in proving the EU can be a strong player both in its neighbourhood and globally. Given what is at stake, what are the Commission’s strategic and policymaking priorities for the next five years? With the discussions on the future EU budget ongoing, what areas will be prioritized when member states come to make decisions between competing objectives? Does the way the EU is perceived externally depend on its member states’ ability to put on a united front when it comes to the most pressing global challenges?

Finally, is this ambitious geopolitical vision deliverable within the EU’s existing structures? If not, are member states ready to give up more control for a stronger Europe at the EU level?

PLEASE NOTE THIS EVENT IS POSTPONED UNTIL FURTHER NOTICE.

Event attributes

Chatham House Rule

Alina Lyadova

Europe Programme Coordinator




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Webinar: Challenges to Democracy: What is the Future of Democracy in Europe?

Members Event Webinar

30 March 2020 - 6:00pm to 7:00pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Dr Catherine Howe, Director, Democracy Society

Hans Kundnani, Senior Research Fellow, Europe Programme, Chatham House

Chair: Thomas Raines, Director, Europe Programme, Chatham House

PLEASE NOTE: THIS EVENT HAS BEEN CANCELLED.

There is a widespread sense that liberal democracy is in crisis but little consensus about how to understand it. While some attribute this crisis to the rise of populist figures, movements and parties, others see populism as a response to a deeper hollowing out of democracy during the last several decades. Some blame the development of digital technology – in particular the emergence of social media – while others argue that the correlation between the development of digital technology and the perceived corrosion of democracy is exaggerated or that it has facilitated greater participation in politics from traditionally under-represented demographics in a way that was not previously possible.

Launching the Chatham House research paper The Future of Democracy in Europe, this panel will discuss how liberal democracy is evolving against the background of social and technological change. What are the challenges to liberal democracy in Europe? How should we understand the impact of technology on how democracy in Europe functions? Given the plurality of democratic structures and institutions across the continent, how can democracy in Europe be reinvigorated? And what role can citizens' assemblies and referendums play in making democracy more responsive to citizens?

This event is open to Chatham House Members only. Not a member? Find out more.

For further information on the different types of Chatham House events, visit Our Events Explained.




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Webinar: Labour, Foreign Policy and Internationalism

Members Event Webinar Online Event

25 March 2020 - 6:00pm to 6:45pm

Event participants

Lisa Nandy MP, Member of Parliament for Wigan

Chair: Thomas Raines, Director, Europe Programme, Chatham House

Labour leadership candidate, Lisa Nandy, reflects on the party's foreign policy priorities and makes the case for a foreign policy underpinned by internationalism.

In recent years, the Labour party has struggled to reach cross-party consensus on its foreign policy agenda. While the current leadership election offers the party an opportunity to debate and redefine its position on issues such as immigration, security and Brexit, the extent to which Labour can reconcile its factionalism remains unclear. As Labour undergoes a process of reflection, what kind of foreign policy agenda should the party rally behind that will also appeal to voters outside of its traditional base?

Can the Labour party be unified on its approach to international issues? Is an internationalist foreign policy an attractive choice for voters? And as Brexit tensions persist, what might the party's framework be to ensure new trade deals and partnerships align with fundamental Labour priorities such as workers' rights?




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Virtual Breakfast: Is a Brexit Delay Possible?

Research Event

7 April 2020 - 8:30am to 9:30am

Event participants

Gavin Barwell, Downing Street Chief of Staff to Prime Minister Theresa May (2017-19)
Chair: Thomas Raines, Director, Europe Programme, Chatham House

Please note this an online-only event.

According to a previously agreed timetable for phase two of Brexit talks, negotiations on the future EU-UK trade relations were scheduled to begin in March. Then a global pandemic hit. Despite the ongoing COVID-19 outbreak, the UK government insists that the Brexit negotiations are on track and there are currently no plans to extend the transition period beyond 2020.

However, the original timetable for trade talks was already widely seen as extremely constrained. Can negotiations still be done in time? With the decision on any possible extension to be made by July at the latest, can the two sides make sufficient progress by that point? Or would the ongoing public health crisis make requesting an extension to the transition period more politically viable for the UK government? Finally, if there is no extension, could Britain still leave the EU with no deal?

In this webinar, the speaker will discuss how the need to manage other challenges, such as the current COVID-19 outbreak, might affect the government’s approach to the negotiations with the EU. He will also share his insights on what to expect from the second phase of negotiations and on the most important lessons from phase one. 

Alina Lyadova

Europe Programme Coordinator




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Webinar: European Democracy in the Last 100 Years: Economic Crises and Political Upheaval

Members Event Webinar

6 May 2020 - 1:00pm to 2:00pm

Event participants

Pepijn Bergsen, Research Fellow, Europe Programme, Chatham House

Dr Sheri Berman, Professor of Political Science, Barnard College

Chair: Hans Kundnani, Senior Research Fellow, Europe Programme, Chatham House

 

In the last 100 years, global economic crises from the Great Depression of the 1930s to the 2008 financial crash have contributed to significant political changes in Europe, often leading to a rise in popularity for extremist parties and politics. As Europe contends with a perceived crisis of democracy - now compounded by the varied responses to the coronavirus outbreak - how should we understand the relationship between externally-driven economic crises, political upheaval and democracy?

The panellists will consider the parallels between the political responses to some of the greatest economic crises Europe has experienced in the last century. Given that economic crises often transcend borders, why does political disruption vary between democracies? What can history tell us about the potential political impact of the unfolding COVID-19-related economic crisis? And will the unprecedented financial interventions by governments across Europe fundamentally change the expectations citizens have of the role government should play in their lives?

This event is based on a recent article in The World Today by Hans Kundnani and Pepijn Bergsen who are both researchers in Chatham House's Europe Programme. 'Crawling from the Wreckage' is the first in a series of articles that look at key themes in European political discourse from the last century. You can read the article here

This event is open to Chatham House Members. Not a member? Find out more.




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The multilevel identity politics of the 2019 Eurovision Song Contest

7 May 2020 , Volume 96, Number 3

Galia Press-Barnathan and Naama Lutz

This article uses the 2019 Eurovision Song Contest (ESC) that took place in Tel Aviv to explore how cultural mega-events serve both as political arenas and as tools for identity construction, negotiation and contestation. These processes of identity politics are all conducted across national–subnational–international–transnational levels. The hosting of mega-events fleshes out these multiple processes in a very strong manner. We first discuss the politics of hosting mega-events in general. We then examine the identity politics associated more specifically with the Eurovision Song Contest, before examining in depth the complex forms of identity politics emerging around the competition following the 2018 Israeli victory. We suggest that it is important to study together the multiple processes—domestic, international and transnational—of identity politics that take place around the competition, as they interact with each other. Consequently, we follow the various stakeholders involved at these different levels and their interactions. We examine the internal identity negotiation process in Israel surrounding the event, the critical actors debating how to use the stage to challenge the liberal, western, ‘normal’ identity Israel hoped to project in the contest and how other stakeholders (participating states, national broadcasting agencies, participating artists) reacted to them, and finally we examine the behaviour of the institution in charge, the European Broadcasting Union, and national governments. We contribute to the study of mega-events as fields of contestation, to the understanding of the complex, multilevel nature of national identity construction, negotiation and contestation in the current era, and more broadly to the role that popular culture plays in this context.




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12th International Forum on Illegal, Unreported and Unregulated Fishing

Research Event

18 May 2020 - 2:00pm to 22 May 2020 - 3:30pm
Add to Calendar
The 12th International Forum on Illegal, Unreported and Unregulated Fishing was originally scheduled to take place 19-20 March 2020 at Chatham House in London, but was postponed due to COVID-19. We are excited to announce that we have decided to transform the 2020 conference into a series of webinars, delivering the forum discussions over the course of a week (18-22 May 2020). The foci of these exciting sessions include a discussion on the importance of international cooperation to end IUU fishing; the interplay between subsidies and IUU practices; the particular impact of IUU fishing on women and gender relations; transparency; new technologies, and a contextual exploration of IUU fishing in Southeast Asia.
 
Many of the excellent panellists confirmed for the in-person event in March have agreed to participate in this digital version of the IUU Fishing Forum. The online format also provides new opportunities; we hope to reach new, larger and more geographically diverse audiences around the world.
 
The agenda, along with the registration links for the sessions, will be published shortly.

Anna Aberg

Research Analyst, Energy, Environment and Resources Programme
020 7314 3629




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Breaking the Habit: Why Major Oil Companies Are Not ‘Paris-Aligned’

Invitation Only Research Event

23 October 2019 - 8:30am to 10:00am

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

Andrew Grant, Carbon Tracker Initiative
Chair: Siân Bradley, Research Fellow, Energy, Environment and Resources, Chatham House

The investment community is increasingly seeking to assess the alignment of their portfolios with the Paris Agreement. In a recent update to their Two Degrees of Separation report, Carbon Tracker assessed the capital expenditure of listed oil and gas producers against ‘well below’ 2C targets, and for the first time, against short-term actions at the project level.

The speaker will present the key findings of the report and will argue that every oil major is betting heavily against a low-carbon world by investing in projects that are contrary to the Paris goals.

This roundtable discussion will further explore the report findings and consider what investors, regulators and oil and gas companies can do to encourage alignment  with the Paris Agreement ahead of 2020.  

Attendance at this event is by invitation only.

Event attributes

Chatham House Rule




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Iseoluwa Akintunde

Mo Ibrahim Foundation Academy Fellow, Energy, Environment and Resources Programme

Biography

Iseoluwa is Mo Ibrahim Fellow in the Energy, Environment and Resources programme where his research examines the international and national institutions responsible for the effectiveness of climate finance in developing countries, and how these frameworks interact with those of development assistance.

He is qualified to practice law in Nigeria and has worked with a leading Nigerian law firm where he provided legal, policy and institutional advisories on environmental, natural resources, energy and climate change, and anti-corruption issues.

He was an Erin JC Arsenault Fellow in Space Governance and holds a Master of Laws degree in Air and Space Law from the McGill Institute of Air and Space Law.

Iseoluwa was previously a visiting researcher at the International Centre for Climate Change and Development, Bangladesh and the Department of Climate Change of the Federal Ministry of Environment in Nigeria where he researched on the governance of climate finance in developing countries.

His broader research interests include the governance framework for the exploitation of the mineral resources in outer space.

Areas of expertise

  • Climate finance and development assistance
  • The legal regime for the exploitation of the mineral resources in outer space, the Moon and celestial bodies
  • International air and space law
  • International law, international environmental law and governance

Past experience

2019Researcher, Centre for International Governance Innovation, Waterloo Canada
2018Visiting researcher, Department of Climate Change, Federal Ministry of Environment, Abuja Nigeria
2018Visiting researcher, International Centre for Climate Change and Development, Dhaka Bangladesh 
2013 - presentAssociate, Wole Olanipekun & Co., Lagos Nigeria