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priority setting partnership on placental pathology: consensus recommendations for placental research
Get PDFIntroductionThe placenta supports the metabolic and respiratory requirements of the fetus. Placental disorders, caused by various pathophysiological mechanisms, may result in adverse pregnancy and neonatal outcomes. Knowledge gaps remain in the understanding, reporting and interpretation of placental pathology relating to clinical conditions. This project aimed to collaboratively identify the most important unanswered research questions related to placental pathology.MethodsAn international Priority Setting Partnership (PSP) was conducted, involving (perinatal) pathologists, obstetricians, paediatrician-neonatologists, midwives, and scientists with expertise in placental pathology. In the first survey, participants identified their three most important unanswered research questions. Afterwards literature was reviewed for evidence on the proposed questions. In a second survey, participants ranked the most important questions from an initial long-list. The top-ranked questions were then discussed and finalized in a 1-h online consensus workshop.ResultsNinety participants completed the first survey. The majority of stakeholders were perinatal pathologists (n = 39 (43.3 %) and most were based in Europe (n = 43 (47.8 %). 270 questions were submitted; after review, these were subdivided into 32 overarching questions. The second ranking survey was completed by 53 participants. Twenty-five participants attended the online workshop, which reached consensus on the top 10. The questions focus, among others, on causes, recurrence risk, consistency of reporting, diagnosing tools and potential use of artificial intelligence.DiscussionFollowing this international PSP, the top 10 prioritized research questions on placental pathology have been identified. This will inform the research agenda for funders and policy-makers, and is intended to improve care for patients suffering from placental insufficiency.Patholog
Majorana-metal transition in a disordered superconductor: percolation in a landscape of topological domain walls
Get PDFTheoretical Physic
A fasting-mimicking diet programme reduces liver fat and liver inflammation/fibrosis measured by magnetic resonance imaging in patients with type 2 diabetes
No full textBackground & aims: This study aimed to assess whether a fasting-mimicking diet (FMD) programme as an adjunct to usual care can reduce liver fat and liver inflammation/fibrosis as measured by Magnetic Resonance Imaging (MRI) in patients with type 2 diabetes. Methods: This study analyses secondary outcomes of the Fasting In diabetes Treatment (FIT) trial, which was a randomised, controlled, assessor-blinded trial in which people with type 2 diabetes using metformin only and/or diet alone for glycaemic control were randomised to receive 5-consecutive day cycles of FMD monthly as adjunct to usual care or usual care only for twelve months. Laboratory measurements, anthropometric measurements and MRI were performed at baseline, 6 and 12 months. Two MRI-derived biomarkers were measured: proton density fat-fraction (PDFF), a biomarker for liver fat, and iron content corrected T1 (cT1), a biomarker for liver inflammation/fibrosis. Results: Data were available of 89 participants who completed baseline visits including MRI (n = 48 in the FMD group and n = 41 in the control group). Intention-to-treat analyses, using linear mixed models, revealed significant adjusted estimated treatment effects of the FMD on PDFF (-2.8 %, 95 % CI -4.7 to -0.8, p = 5.6 %. In the FMD and control group combined, every percent decrease in PDFF was associated with a decrease in HbA1c of 0.75 mmol/mol (95 % CI 0.51 to 0.99), fasting glucose of 0.14 mmol/L (95 % CI 0.08 to 0.20), triglycerides of 0.04 mmol/L (95 % CI 0.02 to 0.07), total cholesterol of 0.03 mmol/L (95 % CI 0.01 to 0.05) and weight of 0.52 kg (CI 0.33 to 0.70). Every millisecond decrease in cT1 was associated with a decrease in HbA1c of 0.05 mmol/mol (95 % CI 0.02 to 0.08), fasting glucose of 0.01 mmol/L (95 % CI 0.00 to 0.02) and weight of 0.04 kg (CI 0.01 to 0.06). Conclusion: Following an FMD programme for 5-consecutive days per month for twelve months reduces both liver PDFF and cT1 MRI-derived biomarkers in patients with type 2 diabetes, indicating a reduction in liver fat and liver inflammation/fibrosis. Decreases in PDFF and cT1 are associated with decreases in HbA1c, fasting glucose, triglycerides and weight. Decrease in PDFF was also associated with a decrease in total cholesterol. Monthly cycles of an FMD appear to be a valuable adjunct to regular treatment of type 2 diabetes.Public Health and primary carePrevention, Population and Disease management (PrePoD
Policy brief - Europe’s strategic dilemma: responding to MENA’s transformations
No full textRegarding the EU's 'strategic dilemma', the tentative conclusion appears to be that there is little dilemma left: the EU has moved from a foreign policy of dialogue in the 1990s, to one called 'principled pragmatism' in 2016, to a policy that appears to be mostly driven by pragmatism and self-interest, particularly in the domains of security, migration and energy. While this new European policy may be required by today's geopolitical developments, it also carries certain risks. First, if the geopolitical merits of human rights and multilateralism (as still proclaimed by the EU) are not sustained in any form, they risk losing their relevance. Second, not adhering to the self- proclaimed European values of international law and humanitarian and democratic principles may be detrimental to the EU's image. Finally, the EU has in the past decade repeatedly been criticized for too little self-reflection on past failed efforts in that region and therefore runs the distinct risk to maintain that attitude when effecting new policies in the region.Middle Eastern Studie
The looming enforcement crisis in European digital policy: a rule-of-law centered path forward
Get PDFThe progression of EU law: Accommodating change and upholding value
Understanding the utilization of indigenous institutions: the case of Wonosobo, Central Java, Indonesia
Get PDFEnvironmental BiologyCultural antropology and development sociolog
In clinical hand osteoarthritis research, self-reported pain questionnaires do not reflect the patient experience
Get PDFObjectivePain in hand osteoarthritis (OA) is evaluated with repeated pain questionnaires. It is unclear whether these questionnaires adequately capture changes in pain recalled by patients. This study investigated whether changes on pain questionnaires (real-time evaluation) correspond to recalled pain.MethodsData from hand OA patients from the HOSTAS cohort (four one-yearly) and HOPE trial (one six-week interval) were used. Pain was measured with the Australian/Canadian hand Osteoarthritis Index (AUSCAN, range 0–20) and a recall question (how is the pain compared with your last visit). Changes in AUSCAN pain were categorized into improved (≤−1), stable or worsened pain (≥1) and compared with the recall question using Cohen’s kappa and percentage agreement. We determined concordance between measurement methods, and investigated associations of mental well-being and illness perceptions with concordance using generalized estimating equations (GEE).ResultsOf 708 intervals from HOSTAS (307 patients, 82% women, mean age 61.0 years, mean AUSCAN 9.1), AUSCAN changes and recall were concordant in 42% (Cohen’s kappa 0.13). There was concordance in 47% of 86 intervals (Cohen’s kappa 0.14) from the HOPE trial (86 patients, 80% women, mean age 63.5, mean AUSCAN 10.7). The most frequent recall answer was worsened pain in the HOSTAS (60%), improved pain in the HOPE trial (76%). In both studies, AUSCAN pain most frequently improved. Depression and anxiety showed no association with concordance.ConclusionChanges in repeatedly measured AUSCAN pain often differ from the recalled course of pain over the same period. This has profound implications for evaluating patient-reported pain in clinical trials.Pathophysiology and treatment of rheumatic disease
IDH-mutant astrocytomas with primitive neuronal component have a distinct methylation profile and a higher risk of leptomeningeal spread
Get PDFIDH-mutant astrocytomas are diffuse gliomas that are defined by characteristic mutations in IDH1 or IDH2 and do not have complete 1p/19q co-deletion. The established grading criteria include histological features of brisk mitotic activity (grade 3) and necrosis and/or microvascular proliferation (grade 4). In addition, homozygous deletion of the CDKN2A/B locus has recently been implemented as a molecular marker for grade 4 IDH-mutant astrocytomas. Here, we describe a subgroup of high-grade IDH-mutant astrocytomas characterised by a primitive neuronal component based on histology and a distinct DNA methylation profile (n = 51, ASTRO PNC). Misinterpretation as carcinoma metastasis was common, since GFAP expression was absent in the primitive neuronal component, whereas TTF-1 expression was detected in 15/19 cases (79%) based on immunohistochemistry. Apart from mutations in IDH1, TP53, and ATRX, we observed enrichment for alterations in RB1 (n = 19/51, 37%) and MYCN (n = 14/51, 27%). Homozygous CDKN2A/B deletion (n = 1/51, 2%) and CDK4 amplification (n = 3/51, 6%) were relatively rare events. Clinical (n = 31 patients) and survival data (n = 23 patients) indicate a clinical behaviour similar to other CNS WHO grade 4 IDH-mutant astrocytomas, however with an increased risk for leptomeningeal (n = 7) and extra-axial (n = 2) spread. Taken together, ASTRO PNC is defined by a distinct molecular and histological appearance that can mimic metastatic disease and typically follows an aggressive clinical course.Chemical Immunolog
Detection and analysis of Serpin and RP26 specific antibodies for monitoring Schistosoma haematobium transmission
Get PDFBackgroundSchistosoma haematobium is the causative pathogen for urogenital schistosomiasis. To achieve progress towards schistosomiasis elimination, there is a critical need for developing highly sensitive and specific tools to monitor transmission in near-elimination settings. Although antibody detection is a promising approach, it is usually unable to discriminate active infections from past ones. Moreover, crude antigens such as soluble egg antigen (SEA) show cross-reactivity with other parasitic infections, and it is difficult to formulate the standard preparations. To resolve these issues, the performances of recombinant antigens have been evaluated. The antibody responses against recombinant S. haematobium serine-protease inhibitor (ShSerpin) and RP26 were previously shown to reflect active schistosome infection in humans. Furthermore, antibody detection using multiple recombinant antigens has been reported to improve the accuracy of antibody-based assays compared to single-target assays. Therefore, we examined the performances of ShSerpin, RP26 and the mixture of these antigens for detecting S. haematobium low-intensity infection and assessed the potential for transmission monitoring.Methodology/principal findingsWe collected urine and plasma samples from school-aged children in Kwale, Kenya and evaluated S. haematobium prevalence by number of eggs in urine and worm-derived circulating anodic antigen (CAA) in plasma. Among 269 pupils, 50.2% were CAA-positive by the lateral flow test utilizing up-converting phosphor particles (UCP-LF CAA), while only 14.1% were egg-positive. IgG levels to S. haematobium SEA (ShSEA), ShSerpin, RP26, and the mixture of ShSerpin and RP26 were measured by ELISA. The mixture of ShSerpin and RP26 showed the highest sensitivity, 88.7%(125/141)among the four antigens in considering indecisive UCP-LF CAA results as negative.Conclusion/significanceIgG detection against the ShSerpin-RP26 mixture demonstrated better sensitivity for detection of active S. haematobium infection. This recombinant antigen mixture is simpler to produce with higher reproducibility and can potentially replace ShSEA in monitoring transmission under near-elimination settings.Host-parasite interactio