Effect of stem cell source on long-term chimerism and event-free survival in children with primary immunodeficiency disorders after fludarabine and melphalan conditioning regimen

BACKGROUND: Reduced-intensity conditioning (RIC) regimens are increasingly being used in the transplantation of patients with primary immunodeficiency disorders (PIDs), but there are no large studies looking at long-term lineage-specific chimerism. OBJECTIVES: We sought to analyze long-term chimerism and event-free survival in children undergoing transplantation for PIDs using RIC with fludarabine and melphalan (Flu/Melph) and to study the effect of donor type and stem cell source. METHODS: One hundred forty-two children underwent transplantation with RIC by using Flu/Melph and for PIDs by using bone marrow (n = 93) or peripheral blood stem cells (PBSCs; n = 49). Donors were matched unrelated donors (n = 72), mismatched unrelated donors (n = 37), matched sibling donors (n = 14), matched family donors (n = 12), and mismatched family donors (n = 7). RESULTS: Overall survival at a median follow-up of 7.5 years was 78%, irrespective of stem cell source or donor type. When bone marrow was used as the stem cell source, 26% of patients ended up with very low levels of donor chimerism (50% donor chimerism) in all lineages. CONCLUSIONS: On the basis of our experience, we would suggest that PBSCs should be the stem cell source of choice in children with PIDs undergoing transplantation with Flu/Melph RIC from a matched donor source. This is most likely to ensure sustained high-level donor chimerism

Exploring access to end of life care for ethnic minorities with end stage kidney disease through recruitment in action research

BACKGROUND: Variation in provision of palliative care in kidney services and practitioner concerns to provide equitable access led to the development of this study which focussed on the perspectives of South Asian patients and their care providers. As people with a South Asian background experience a higher risk of Type 2 Diabetes (T2DM) and end stage kidney failure (ESKF) compared to the majority population but wait longer for a transplant, there is a need for end of life care to be accessible for this group of patients. Furthermore because non English speakers and people at end of life are often excluded from research there is a dearth of research evidence with which to inform service improvement. This paper aims to explore issues relating to the process of recruitment of patients for a research project which contribute to our understanding of access to end of life care for ethnic minority patients in the kidney setting. METHODS: The study employed an action research methodology with interviews and focus groups to capture and reflect on the process of engaging with South Asian patients about end of life care. Researchers and kidney care clinicians on four NHS sites in the UK recruited South Asian patients with ESKF who were requiring end of life care to take part in individual interviews; and other clinicians who provided care to South Asian kidney patients at end of life to take part in focus groups exploring end of life care issues. In action research planning, action and evaluation are interlinked and data were analysed with emergent themes fed back to care providers through the research cycle. Reflections on the process of patient recruitment generated focus group discussions about access which were analysed thematically and reported here. RESULTS: Sixteen patients were recruited to interview and 45 different care providers took part in 14 focus groups across the sites. The process of recruiting patients to interview and subsequent focus group data highlighted some of the key issues concerning access to end of life care. These were: the identification of patients approaching end of life; and their awareness of end of life care; language barriers and informal carers' roles in mediating communication; and contrasting cultures in end of life kidney care. CONCLUSIONS: Reflection on the process of recruitment in this action research study provided insight into the complex scenario of end of life in kidney care. Some of the emerging issues such as the difficulty identifying patients are likely to be common across all patient groups, whilst others concerning language barriers and third party communication are more specific to ethnic minorities. A focus on South Asian ethnicity contributes to better understanding of patient perspectives and generic concepts as well as access to end of life kidney care for this group of patients in the UK. Action research was a useful methodology for achieving this and for informing future research to include informal carers and other ethnic groups.Peer reviewedFinal Published versio

Multi-electron giant dipole resonances of atoms in crossed electric and magnetic fields

Multi-electron giant dipole resonances of atoms in crossed electric and magnetic fields are investigated. Stationary configurations corresponding to a highly symmetric arrangement of the electrons on a decentered circle are derived, and a normal-mode stability analysis is performed. A classification of the various modes, which are dominated either by the magnetic or Coulomb interactions, is provided. A six-dimensional wave-packet dynamical study, based on the MCTDH approach, is accomplished for the two-electron resonances, yielding in particular lifetimes of more than 0.1 $\mu$s for strong electric fields.Comment: 7 pages, 3 figure

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Interpolated wave functions for nonadiabatic simulations with the fixed-node quantum Monte Carlo method

Simulating nonadiabatic effects with many-body wave function approaches is an open field with many challenges. Recent interest has been driven by new algorithmic developments and improved theoretical understanding of properties unique to electron-ion wave functions. Fixed-node diffusion Monte Caro is one technique that has shown promising results for simulating electron-ion systems. In particular, we focus on the CH molecule for which previous results suggested a relatively significant contribution to the energy from nonadiabatic effects. We propose a new wave function ansatz for diatomic systems which involves interpolating the determinant coefficients calculated from configuration interaction methods. We find this to be an improvement beyond previous wave function forms that have been considered. The calculated nonadiabatic contribution to the energy in the CH molecule is reduced compared to our previous results, but still remains the largest among the molecules under consideration.Comment: 7 pages, 3 figure

5S-IGS rDNA in wind-pollinated trees (Fagus L.) encapsulates 55 million years of reticulate evolution and hybrid origins of modern species

Standard models of plant speciation assume strictly dichotomous genealogies in which a species, the ancestor, is replaced by two offspring species. The reality in wind‐pollinated trees with long evolutionary histories is more complex: species evolve from other species through isolation when genetic drift exceeds gene flow; lineage mixing can give rise to new species (hybrid taxa such as nothospecies and allopolyploids). The multi‐copy, potentially multi‐locus 5S rDNA is one of few gene regions conserving signal from dichotomous and reticulate evolutionary processes down to the level of intra‐genomic recombination. Therefore, it can provide unique insights into the dynamic speciation processes of lineages that diversified tens of millions of years ago. Here, we provide the first high‐throughput sequencing (HTS) of the 5S intergenic spacers (5S‐IGS) for a lineage of wind‐pollinated subtropical to temperate trees, the Fagus crenata – F. sylvatica s.l. lineage, and its distant relative F. japonica. The observed 4963 unique 5S‐IGS variants reflect a complex history of hybrid origins, lineage sorting, mixing via secondary gene flow, and intra‐genomic competition between two or more paralogous‐homoeologous 5S rDNA lineages. We show that modern species are genetic mosaics and represent a striking case of ongoing reticulate evolution during the past 55 million years

The role of healthcare professionals in encouraging parents to see and hold their stillborn baby: a meta-synthesis of qualitative studies.

Background: Globally, during 2013 there were three million recorded stillbirths. Where clinical guidelines exist some recommend that professionals do not encourage parental contact. The guidance is based on quantitative evidence that seeing and holding the baby is not beneficial for everyone, but has been challenged by bereaved parents' organisations. We aim to inform future guideline development through a synthesis of qualitative studies reporting data relevant to the research question; how does the approach of healthcare professionals to seeing and holding the baby following stillbirth impact parents views and experiences? Methods/Findings: Using a predetermined search strategy of PubMed and PsychINFO we identified robust qualitative studies reporting bereaved parental views and/or experiences relating to seeing and holding their stillborn baby (final search 24 February, 2014). Eligible studies were English language, reporting parental views, with gestational loss >20weeks. Quality was independently assessed by three authors using a validated tool. We used meta-ethnographic techniques to identify key themes and a line of argument synthesis. We included 12 papers, representing the views of 333 parents (156 mothers, 150 fathers, and 27 couples) from six countries. The final themes were: "[Still]birth: Nature of care is paramount", "Real babies: Perfect beauties, monsters and spectres", and "Opportunity of a lifetime lost." Our line-of-argument synthesis highlights the contrast between all parents need to know their baby, with the time around birth being the only time memories can be made, and the variable ability that parents have to articulate their preferences at that time. Thus, we hypothesised that how health professionals approach contact between parents and their stillborn baby demands a degree of active management. An important limitation of this paper is all included studies originated from high income, westernised countries raising questions about the findings transferability to other cultural contexts. We do not offer new evidence to answer the question "Should parents see and hold their stillborn baby?", instead our findings advance understanding of how professionals can support parents to make appropriate decisions in a novel, highly charged and dynamic situation. Conclusions: Guidelines could be more specific in their recommendations regarding parental contact. The role of healthcare professionals in encouraging parents to see and hold their stillborn baby is paramount. Parental choice not to see their baby, apprehension, or uncertainty should be continuously revisited in the hours after birth as the opportunity for contact is fleeting and final

InternationaL cross-sectIonAl and longItudinal assessment on aSthma cONtrol in European adult patients : the LIAISON study protocol

The study is funded by Chiesi Farmaceutici S.p.A., Parma, ItalyPeer reviewedPublisher PD

New insights into risk factors for transplant-associated thrombotic microangiopathy in pediatric HSCT

This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation–based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA was threefold higher among patients who received >1 transplant. TA-TMA rates were significantly higher among patients with acute graft-versus-host disease (aGVHD) grades III to IV vs aGVHD grade 0 to II. On multivariate analysis, the presence of active comorbidity, >1 transplant, aGVHD grade III to IV were risk factors for TA-TMA (odds ratio [OR]: 5.1, 5.2, and 26.9; respectively), whereas the use of cyclosporine A/tacrolimus-based GVHD prophylaxis was not a risk factor for TA-TMA (OR: 0.3). Active comorbidity, subsequent transplant, and aGVHD grades III to IV were significant risk factors for TA-TMA. TA-TMA might represent a form of a vascular GVHD, and therefore, continuing control of aGVHD is important to prevent worsening of TA-TMA associated with GVHD