| 1. |
- Kahn, Justine M., et al.
(author)
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Subsequent neoplasms and late mortality in children undergoing allogeneic transplantation for nonmalignant diseases
- 2020
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In: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 4:9, s. 2084-2094
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Journal article (peer-reviewed)abstract
- We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). Weincluded 6028 patients (median age, 6 years; interquartile range, 1-11; range, <1 to 20) from the Center for International Blood and Marrow Transplant Research (1995-2012) registry. Standardized mortality ratios (SMRs) in 2-year survivors and standardized incidence ratios (SIRs) were calculated to compare mortality and SN rates with expected rates in the general population. Median follow-up of survivors was 7.8 years. Diagnoses included severe aplastic anemia (SAA; 24%), Fanconi anemia (FA; 10%), other marrow failure (6%), hemoglobinopathy (15%), immunodeficiency (23%), and metabolic/leukodystrophy syndrome (22%). Ten-year survival was 93% (95% confidence interval [95% CI], 92% to 94%; SMR, 4.2; 95% CI, 3.7-4.8). Seventy-one patients developed SNs (1.2%). Incidence was highest in FA (5.5%), SAA (1.1%), and other marrow failure syndromes (1.7%); for other NMDs, incidence was <1%. Hematologic (27%), oropharyngeal (25%), and skin cancers (13%) were most common. Leukemia risk was highest in the first 5 years posttransplantation; oropharyngeal, skin, liver, and thyroid tumors primarily occurred after 5 years. Despite a low number of SNs, patients had an 11-fold increased SN risk (SIR, 11; 95% CI, 8.9-13.9) compared with the general population. We report excellent long-term survival and low SN incidence in an international cohort of children undergoing HCT for NMDs. The risk of SN development was highest in patients with FA and marrow failure syndromes, highlighting the need for long-term posttransplantation surveillance in this population.
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| 2. |
- Taylor, Alison M., et al.
(author)
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Calmodulin inhibitors improve erythropoiesis in Diamond-Blackfan anemia
- 2020
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In: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6242 .- 1946-6234. ; 12:566
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Journal article (peer-reviewed)abstract
- Diamond-Blackfan anemia (DBA) is a rare hematopoietic disease characterized by a block in red cell differentiation. Most DBA cases are caused by mutations in ribosomal proteins and characterized by higher than normal activity of the tumor suppressor p53. Higher p53 activity is thought to contribute to DBA phenotypes by inducing apoptosis during red blood cell differentiation. Currently, there are few therapies available for patients with DBA. We performed a chemical screen using zebrafish ribosomal small subunit protein 29 (rps29) mutant embryos that have a p53-dependent anemia and identified calmodulin inhibitors that rescued the phenotype. Our studies demonstrated that calmodulin inhibitors attenuated p53 protein amount and activity. Treatment with calmodulin inhibitors led to decreased p53 translation and accumulation but does not affect p53 stability. A U.S. Food and Drug Administration-approved calmodulin inhibitor, trifluoperazine, rescued hematopoietic phenotypes of DBA models in vivo in zebrafish and mouse models. In addition, trifluoperazine rescued these phenotypes in human CD34+ hematopoietic stem and progenitor cells. Erythroid differentiation was also improved in CD34+ cells isolated from a patient with DBA. This work uncovers a potential avenue of therapeutic development for patients with DBA.
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| 3. |
- Bertels, Xander, et al.
(author)
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Phenotyping asthma with airflow obstruction in middle-aged and older adults : a CADSET clinical research collaboration
- 2023
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In: BMJ open respiratory research. - : BMJ Publishing Group Ltd. - 2052-4439. ; 10:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: The prevalence and clinical profile of asthma with airflow obstruction (AO) remain uncertain. We aimed to phenotype AO in population- and clinic-based cohorts.METHODS: This cross-sectional multicohort study included adults ≥50 years from nine CADSET cohorts with spirometry data (N=69 789). AO was defined as ever diagnosed asthma with pre-BD or post-BD FEV1/FVC <0.7 in population-based and clinic-based cohorts, respectively. Clinical characteristics and comorbidities of AO were compared with asthma without airflow obstruction (asthma-only) and chronic obstructive pulmonary disease (COPD) without asthma history (COPD-only). ORs for comorbidities adjusted for age, sex, smoking status and body mass index (BMI) were meta-analysed using a random effects model.RESULTS: The prevalence of AO was 2.1% (95% CI 2.0% to 2.2%) in population-based, 21.1% (95% CI 18.6% to 23.8%) in asthma-based and 16.9% (95% CI 15.8% to 17.9%) in COPD-based cohorts. AO patients had more often clinically relevant dyspnoea (modified Medical Research Council score ≥2) than asthma-only (+14.4 and +14.7 percentage points) and COPD-only (+24.0 and +5.0 percentage points) in population-based and clinic-based cohorts, respectively. AO patients had more often elevated blood eosinophil counts (>300 cells/µL), although only significant in population-based cohorts. Compared with asthma-only, AO patients were more often men, current smokers, with a lower BMI, had less often obesity and had more often chronic bronchitis. Compared with COPD-only, AO patients were younger, less often current smokers and had less pack-years. In the general population, AO patients had a higher risk of coronary artery disease than asthma-only and COPD-only (OR=2.09 (95% CI 1.26 to 3.47) and OR=1.89 (95% CI 1.10 to 3.24), respectively) and of depression (OR=1.41 (95% CI 1.19 to 1.67)), osteoporosis (OR=2.30 (95% CI 1.43 to 3.72)) and gastro-oesophageal reflux disease (OR=1.68 (95% CI 1.06 to 2.68)) than COPD-only, independent of age, sex, smoking status and BMI.CONCLUSIONS: AO is a relatively prevalent respiratory phenotype associated with more dyspnoea and a higher risk of coronary artery disease and elevated blood eosinophil counts in the general population compared with both asthma-only and COPD-only.
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| 4. |
- Cable, Jennifer, et al.
(author)
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Progress in vaccine development for infectious diseases : a Keystone Symposia report
- 2023
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In: Annals of the New York Academy of Sciences. - : John Wiley & Sons. - 0077-8923 .- 1749-6632. ; 1524:1, s. 65-86
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Journal article (peer-reviewed)abstract
- The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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| 5. |
- Khaleva, E, et al.
(author)
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Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
- 2023
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
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Journal article (peer-reviewed)abstract
- Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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| 6. |
- Khaleva, E, et al.
(author)
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Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
- 2023
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In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
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Journal article (peer-reviewed)abstract
- Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
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| 7. |
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| 8. |
- Braga Jr, Iran Mesquita, et al.
(author)
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Joint Resource Allocation and Transceiver Design for Sum-Rate Maximization Under Latency Constraints in Multicell MU-MIMO Systems
- 2021
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In: IEEE Transactions on Communications. - : Institute of Electrical and Electronics Engineers (IEEE). - 0090-6778 .- 1558-0857. ; 69:7, s. 1-1
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Journal article (peer-reviewed)abstract
- Due to the continuous advancements of orthogonal frequency division multiplexing (OFDM) and multiple antenna techniques, multiuser multiple input multiple output (MU-MIMO) OFDM is a key enabler of both fourth and fifth generation networks. In this paper, we consider the problem of weighted sum-rate maximization under latency constraints in finite buffer multicell MU-MIMO OFDM systems. Unlike previous works, the optimization variables include the transceiver beamforming vectors, the scheduled packet size and the resources in the frequency and power domains. This problem is motivated by the observation that multicell MU-MIMO OFDM systems serve multiple quality of service classes and the system performance depends critically on both the transceiver design and the scheduling algorithm. Since this problem is non-convex, we resort to the max-plus queuing method and successive convex approximation. We propose both centralized and decentralized solutions, in which practical design aspects, such as signaling overhead, are considered. Finally, we compare the proposed framework with state-of-the-art algorithms in relevant scenarios, assuming a realistic channel model with space, frequency and time correlations. Numerical results indicate that our design provides significant gains over designs based on the wide-spread saturated buffers assumption, while also outperforming algorithms that consider a finite-buffer model. Due to the continuous advancements of orthogonal frequency division multiplexing (OFDM) and multiple antenna techniques, multiuser multiple input multiple output (MU-MIMO) OFDM is a key enabler of both fourth and fifth generation networks. In this paper, we consider the problem of weighted sum-rate maximization under latency constraints in finite buffer multicell MU-MIMO OFDM systems. Unlike previous works, the optimization variables include the transceiver beamforming vectors, the scheduled packet size and the resources in the frequency and power domains. This problem is motivated by the observation that multicell MU-MIMO OFDM systems serve multiple quality of service classes and the system performance depends critically on both the transceiver design and the scheduling algorithm. Since this problem is non-convex, we resort to the max-plus queuing method and successive convex approximation. We propose both centralized and decentralized solutions, in which practical design aspects, such as signaling overhead, are considered. Finally, we compare the proposed framework with state-of-the-art algorithms in relevant scenarios, assuming a realistic channel model with space, frequency and time correlations. Numerical results indicate that our design provides significant gains over designs based on the widespread saturated buffers assumption, while also outperforming algorithms that consider a finite-buffer model.
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| 9. |
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| 10. |
- Rodriguez-Ezpeleta, Naiara, et al.
(author)
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Trade-offs between reducing complex terminology and producing accurate interpretations from environmental DNA : Comment on “Environmental DNA: What's behind the term?” by Pawlowski et al., (2020)
- 2021
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In: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 30:19, s. 4601-4605
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Journal article (peer-reviewed)abstract
- In a recent paper, “Environmental DNA: What's behind the term? Clarifying the terminology and recommendations for its future use in biomonitoring,” Pawlowski et al. argue that the term eDNA should be used to refer to the pool of DNA isolated from environmental samples, as opposed to only extra-organismal DNA from macro-organisms. We agree with this view. However, we are concerned that their proposed two-level terminology specifying sampling environment and targeted taxa is overly simplistic and might hinder rather than improve clear communication about environmental DNA and its use in biomonitoring. This terminology is based on categories that are often difficult to assign and uninformative, and it overlooks a fundamental distinction within eDNA: the type of DNA (organismal or extra-organismal) from which ecological interpretations are derived.
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