Conditioning regimens for haematopoietic cell transplantation in primary immunodeficiencies

Purpose of ReviewHematopoietic cell transplantation (HCT) is an established curative treatment for children with primary immunodeficiencies. This article reviews the latest developments in conditioning regimens for primary immunodeficiency (PID). It focuses on data regarding transplant outcomes according to newer reduced toxicity conditioning regimens used in HCT for PID.Recent FindingsConventional myeloablative conditioning regimens are associated with significant acute toxicities, transplant-related mortality, and late effects such as infertility. Reduced toxicity conditioning regimens have had significant positive impacts on HCT outcome, and there are now well-established strategies in children with PID. Treosulfan has emerged as a promising preparative agent. Use of a peripheral stem cell source has been shown to be associated with better donor chimerism in patients receiving reduced toxicity conditioning. Minimal conditioning regimens using monoclonal antibodies are in clinical trials with promising results thus far.SummaryReduced toxicity conditioning has emerged as standard of care for PID and has resulted in improved transplant survival for patients with significant comorbidities.</div

Deconstructing classical water models at interfaces and in bulk

Using concepts from perturbation and local molecular field theories of liquids we divide the potential of the SPC/E water model into short and long ranged parts. The short ranged parts define a minimal reference network model that captures very well the structure of the local hydrogen bond network in bulk water while ignoring effects of the remaining long ranged interactions. This deconstruction can provide insight into the different roles that the local hydrogen bond network, dispersion forces, and long ranged dipolar interactions play in determining a variety of properties of SPC/E and related classical models of water. Here we focus on the anomalous behavior of the internal pressure and the temperature dependence of the density of bulk water. We further utilize these short ranged models along with local molecular field theory to quantify the influence of these interactions on the structure of hydrophobic interfaces and the crossover from small to large scale hydration behavior. The implications of our findings for theories of hydrophobicity and possible refinements of classical water models are also discussed

Communication is key: a study of the development of communication key skills in China

Different countries offer alternative curricula around what might be designated language, literacy and/or communication. This paper focuses on the latter which has typically been associated with vocational education and often labelled a ‘key’ or ‘core’ skill that forms part of a wider set of life and employability skills. In recent years, as China has emerged as a global economy, education has been significant in its policy and development. This research explores staff and student responses to the introduction of a key skills communication course in three Chinese further education vocational colleges. The initiative was prompted by research in China which had suggested that communication is important not just for education (Ye and Li 2007) but also for employability, and that the ability to communicate effectively could be instrumental in individuals’ success and development (Tong and Zhong 2008). It explores what communication key skills might mean in a Chinese context and questions notions of transferability and of competence and performance in communication. It analyses how motivation could affect learner success and the relationship of pedagogy to curriculum and, finally, it considers how communication might be an element in the longer-term social and political development of critical literacies

Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine 6 thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan-vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged = 5 years remains a risk factor for overall survival.Transplantation and immunomodulatio

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Clinical and immunological outcome after paediatric stem cell transplantation in inborn errors of immunity

This thesis examines the clinical and immunological outcome after paediatric stem cell transplantation in inborn errors of immunity (IEI). First part reviews the general principles of haematopoietic cell transplantation (HCT) in IEI. The second part of this thesis focuses on practice pattern changes over the past three decades in the field of transplant for non-SCID IEI. The third part of this thesis analyses the outcome after HCT in IEI using ex-vivo T cell depleted mismatched grafts and compares the HCT outcomes between T deplete HLA-mismatched grafts and T-replete HLA-matched family/unrelated grafts. Part 4 focuses on late effects of HCT, particularly post-transplant autoimmunity and malignancy post-HCT in IEI. The final part explores the potential future directions of research into the diversity in the use of HCT in IEI.</p

Clinical and immunological outcome after paediatric stem cell transplantation in inborn errors of immunity

This thesis examines the clinical and immunological outcome after paediatric stem cell transplantation in inborn errors of immunity (IEI). First part reviews the general principles of haematopoietic cell transplantation (HCT) in IEI. The second part of this thesis focuses on practice pattern changes over the past three decades in the field of transplant for non-SCID IEI. The third part of this thesis analyses the outcome after HCT in IEI using ex-vivo T cell depleted mismatched grafts and compares the HCT outcomes between T deplete HLA-mismatched grafts and T-replete HLA-matched family/unrelated grafts. Part 4 focuses on late effects of HCT, particularly post-transplant autoimmunity and malignancy post-HCT in IEI. The final part explores the potential future directions of research into the diversity in the use of HCT in IEI.</p

Clinical and immunological outcome after paediatric stem cell transplantation in inborn errors of immunity

This thesis examines the clinical and immunological outcome after paediatric stem cell transplantation in inborn errors of immunity (IEI). First part reviews the general principles of haematopoietic cell transplantation (HCT) in IEI. The second part of this thesis focuses on practice pattern changes over the past three decades in the field of transplant for non-SCID IEI. The third part of this thesis analyses the outcome after HCT in IEI using ex-vivo T cell depleted mismatched grafts and compares the HCT outcomes between T deplete HLA-mismatched grafts and T-replete HLA-matched family/unrelated grafts. Part 4 focuses on late effects of HCT, particularly post-transplant autoimmunity and malignancy post-HCT in IEI. The final part explores the potential future directions of research into the diversity in the use of HCT in IEI.LUMC / Geneeskund