Quality of group decisions by board members:A hidden-profile experiment

Purpose Reaching decisions in a deliberative manner is of utmost importance for boards, as their decision-making impacts entire organisations. The current study aims to investigate (1) the quality of group decisions made by board members, (2) their confidence in, satisfaction with, and reflection on the decision-making, and (3) the effect of two discussion procedures on objective decision quality and subjective evaluations of the decision-making. Design/methodology/approach Board members of various Dutch non-profit organisations (N = 141) participated in a group decision-making task and a brief questionnaire. According to the hidden-profile paradigm, information was asymmetrically distributed among group members and should have been pooled to reach the objectively best decision. Half of the groups received one of two discussion procedures (i.e. advocacy decision or decisional balance sheet), while the other half received none. Findings Only a fifth of the groups successfully chose the best decision alternative. The initial majority preference strongly influenced the decision, which indicates that discussion was irrelevant to the outcome. Nevertheless, board members were satisfied with their decision-making. Using a discussion procedure enhanced participants' perception that they adequately weighed the pros and cons, but did not improve objective decision quality or other aspects of the subjective evaluation. These findings suggest that board members are unaware of their biased decision-making, which might hinder improvement. Originality/value Rather than using student samples, this study was the first to have board members participating in a hidden-profile task

Can decision transparency increase citizen trust in regulatory agencies? Evidence from a representative survey experiment

Decision transparency is often proposed as a way to maintain or even increase citizen trust, yet this assumption is still untested in the context of regulatory agencies. We test the effect of transparency of a typical decision tradeoff in regulatory enforcement: granting forbearance or imposing a sanction. We employed a representative survey experiment (n = 1,546) in which we test the effect of transparency in general (providing information about a decision or not) and the effect of specific types of transparency (process or rationale transparency). We do this for agencies supervising financial markets, education, and health care. We find that overall decision transparency significantly increases citizen trust in only two of the three agencies. Rationale transparency has a more pronounced positive effect only for the Education Inspectorate. We conclude that the overall effect of decision transparency is positive but that the nature of the regulatory domain may weaken or strengthen this effect

Markers of NETosis and DAMPs are altered in critically ill COVID-19 patients

Background Coronavirus disease 19 (COVID-19) is known to present with disease severities of varying degree. In its most severe form, infection may lead to respiratory failure and multi-organ dysfunction. Here we study the levels of extracellular histone H3 (H3), neutrophil elastase (NE) and cfDNA in relation to other plasma parameters, including the immune modulators GAS6 and AXL, ICU scoring systems and mortality in patients with severe COVID-19. Methods We measured plasma H3, NE, cfDNA, GAS6 and AXL concentration in plasma of 83 COVID-19-positive and 11 COVID-19-negative patients at admission to the Intensive Care Unit (ICU) at the Uppsala University hospital, a tertiary hospital in Sweden and a total of 333 samples obtained from these patients during the ICU-stay. We determined their correlation with disease severity, organ failure, mortality and other blood parameters. Results H3, NE, cfDNA, GAS6 and AXL were increased in plasma of COVID-19 patients compared to controls. cfDNA and GAS6 decreased in time in in patients surviving to 30 days post ICU admission. Plasma H3 was a common feature of COVID-19 patients, detected in 40% of the patients at ICU admission. Although these measures were not predictive of the final outcome of the disease, they correlated well with parameters of tissue damage (H3 and cfDNA) and neutrophil counts (NE). A subset of samples displayed H3 processing, possibly due to proteolysis. Conclusions Elevated H3 and cfDNA levels in COVID-19 patients illustrate the severity of the cellular damage observed in critically ill COVID-19 patients. The increase in NE indicates the important role of neutrophil response and the process of NETosis in the disease. GAS6 appears as part of an early activated mechanism of response in Covid-19.The study was supported through grants from the dedSciLifeLab/KAW national COVID-19 research program project grant (MH), by Scilifelab, the Knut and Alice Wallenberg Foundation and in part by the Swedish Research Council (RF, grant no 2014-02569 and 2014-07606), and the Netherlands Thrombosis Foundation (GN).N

Presence and evolution of NET markers and DAMPS in critically ill COVID-19 patients

Resumen del trabajo presentado en el 4th European Congress on Thrombosis and Haemostasis, celebrado en Gante (Bélgica), los días 14 y 15 de octubre de 2021Background: The coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection presents with a wide range of disease symptoms. In the more severe patients, COVID-19 is associated with respiratory failure, neutrophil extracellular trap (NET) formation, and multiple organ failure (MOF). Aims: We investigated the presence and evolution of several damage associated molecular patterns (DAMPs) neutrophil markers and immune modulators in a group of 100 COVID-19-positive ICU patients. Methods: Citrated plasma was collected from adult patients with confirmed COVID-19 by PCR detection of SARS-CoV-2 E and N-genes in nasopharyngeal swabs admitted to the intensive care unit (ICU) at Uppsala University hospital, Sweden. Written informed consent was obtained from the patients, or next of kin if the patient was unable to give consent. The Declaration of Helsinki and its subsequent revisions were followed. Plasma concentration of cell free DNA (cfDNA), extracellular histone H3 (H3), neutrophil elastase (NE), myeloperoxidase (MPO) and the cfDNA-MPO complex, and the immune modulators GAS6, and sAXL were measured in all COVID-19-positive and in COVID-19-negative patients and healthy controls. We determined marker levels upon admission, of their evolution, and correlation with disease severity, organ failure, thromboembolic events, mortality, and other blood parameters. Results: The level of cfDNA, H3, NE, MPO, cfDNA-MPO complex, GAS6, and sAXL were all significantly increased in plasma of COVID-19 patients compared to controls. Importantly, a diminution of cfDNA and GAS6 levels over time was observed in patients surviving 30 days after ICU admission. Histone H3 levels were detected in 40% of the COVID-19 patient plasma at ICU admission and the presence of histone H3 during ICU stay was associated with an increased risk of thromboembolic events and secondary infection. Though NET markers were not predictive of 30-day mortality, they correlated with several parameters of tissue damage and neutrophil counts. Summary/Conclusion: The increased presence of cfDNA, H3 and NE, MPO, and MPO-DNA illustrates the severity of cellular damage and indicates activation of NETosis in severe COVID-19 ICU patients. The evolution of cfDNA and Gas6 is able to predict disease prognosis of severely ill COVID-19 patients, where GAS6 appears to be part of an early activated mechanism in response to COVID-19. These data support treatment aimed at the reduction of NET formation in severe COVID-19 patients

Rituximab in early systemic sclerosis

Objectives (1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc). Methods A small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit. Skin biopsies were taken at baseline and month 3. Immunophenotyping of peripheral blood mononuclear cells was performed at every visit, except at months 9 and 18. Adverse events, course of skin and pulmonary involvement and B cell populations in skin and peripheral blood were evaluated. Results In total 16, patients (rituximab n=8, placebo n=8) were included. Twelve patients had diffuse cutaneous SS

Ultrasound measurements of brain structures differ between moderate-late preterm and full-term infants at term equivalent age

Background: Brain growth in moderate preterm (MP; gestational age (GA) 32+0–33+6 weeks) and late preterm infants (LP; GA 34+0–36+6 weeks) may be impaired, even in the absence of brain injury. Aims: The aims of this study were to assess brain measurements of MP and LP infants, and to compare these with full-term infants (GA > 37 weeks) using linear cranial ultrasound (cUS) at term equivalent age (TEA). Study design: cUS data from two prospective cohorts were combined. Two investigators performed offline measurements on standard cUS planes. Eleven brain structures were compared between MP, LP and full-term infants using uni- and multivariable linear regression. Results were adjusted for postmenstrual age at cUS and corrected for multiple testing. Results: Brain measurements of 44 MP, 54 LP and 52 full-term infants were determined on cUS scans at TEA. Biparietal diameter and basal ganglia-insula width were smaller in MP (−9.1 mm and − 1.7 mm, p < 0.001) and LP infants (−7.0 mm and − 1.7 mm, p < 0.001) compared to full-term infants. Corpus callosum – fastigium length was larger in MP (+2.2 mm, p < 0.001) than in full-term infants. No significant differences were found between MP and LP infants. Conclusions: These findings suggest that brain growth in MP and LP infants differs from full-term infants. Whether these differences have clinical implications remains to be investigated

Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential.

Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+) cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential

Retrospective evaluation of the Dutch pre-newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia:What to aim, expect, and evaluate from newborn screening?

Evidence for effectiveness of newborn screening (NBS) for propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is scarce. Prior to implementation in the Netherlands, we aim to estimate the expected health gain of NBS for PA and MMA. In this national retrospective cohort study, the clinical course of 76/83 Dutch PA and MMA patients, diagnosed between January 1979 and July 2019, was evaluated. Five clinical outcome parameters were defined: adverse outcome of the first symptomatic phase, frequency of acute metabolic decompensations (AMD), cognitive function, mitochondrial complications, and treatment-related complications. Outcomes of patients identified by family testing were compared with the outcomes of their index siblings. An adverse outcome due to the first symptomatic phase was recorded in 46% of the clinically diagnosed patients. Outcome of the first symptomatic phase was similar in 5/9 sibling pairs and better in 4/9 pairs. Based on the day of diagnosis of the clinically diagnosed patients and sibling pair analysis, a preliminary estimated reduction of adverse outcome due to the first symptomatic phase from 46% to 36%-38% was calculated. Among the sibling pairs, AMD frequency, cognitive function, mitochondrial, and treatment-related complications were comparable. These results suggest that the health gain of NBS for PA and MMA in overall outcome may be limited, as only a modest decrease of adverse outcomes due to the first symptomatic phase is expected. With current clinical practice, no reduced AMD frequency, improved cognitive function, or reduced frequency of mitochondrial or treatment-related complications can be expected

Retrospective evaluation of the Dutch pre-newborn screening cohort for propionic acidemia and isolated methylmalonic acidemia: What to aim, expect, and evaluate from newborn screening?

Evidence for effectiveness of newborn screening (NBS) for propionic acidemia (PA) and isolated methylmalonic acidemia (MMA) is scarce. Prior to implementation in the Netherlands, we aim to estimate the expected health gain of NBS for PA and MMA. In this national retrospective cohort study, the clinical course of 76/83 Dutch PA and MMA patients, diagnosed between January 1979 and July 2019, was evaluated. Five clinical outcome parameters were defined: adverse outcome of the first symptomatic phase, frequency of acute metabolic decompensations (AMD), cognitive function, mitochondrial complications, and treatment-related complications. Outcomes of patients identified by family testing were compared with the outcomes of their index siblings. An adverse outcome due to the first symptomatic phase was recorded in 46% of the clinically diagnosed patients. Outcome of the first symptomatic phase was similar in 5/9 sibling pairs and better in 4/9 pairs. Based on the day of diagnosis of the clinically diagnosed patients and sibling pair analysis, a preliminary estimated reduction of adverse outcome due to the first symptomatic phase from 46% to 36%-38% was calculated. Among the sibling pairs, AMD frequency, cognitive function, mitochondrial, and treatment-related complications were comparable. These results suggest that the health gain of NBS for PA and MMA in overall outcome may be limited, as only a modest decrease of adverse outcomes due to the first symptomatic phase is expected. With current clinical practice, no reduced AMD frequency, improved cognitive function, or reduced frequency of mitochondrial or treatment-related complications can be expected