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B cells play crucial roles in cell-mediated alloimmune responses. In vitro, B cells can support or regulate indirect T-cell alloreactivity in response to donor antigens on ELISpot and these patterns associate with clinical outcome. Previous reports of associations between B-cell phenotype and function have examined global phenotypes and responses to polyclonal stimuli. We hypothesized that studying antigen-specific B cells, using samples from sensitized patients, would inform further study to identify novel targets for intervention. Using biotinylated HLA proteins, which bind HLA-specific B cells via the B-cell receptor in a dose-dependent fashion, we report the specific phenotype of HLA-binding B cells and define how they associated with patterns of anti-HLA response in interferon-γ ELISpot. HLA-binding class-switched and IgM

Eye tracking technology, checklists and search strategies have been demonstrated as useful aids in image interpretation. A training tool was developed, by the research team, which included these features. This study aimed to evaluate the effect of the training tool on participant image interpretation performance.The study was carried out with reporting radiographers who had either commenced training in chest image interpretation (n = 12) or were trained in musculoskeletal image interpretation (n = 23) (total n = 35). Participants were allocated to a control or intervention group. Participants completed an initial assessment at recruitment and re-attended nine months later for a follow-up assessment. The intervention group were given unlimited access to a digital training tool. During assessments participants interpreted 20 chest images whilst using eye tracking technology (total of 1400 images were interpreted). A confidence level was obtained from participants on their diagnosis and a questionnaire, to obtain demographic data, was completed following the assessment.Improvements were seen in the confidence of intervention group participants (p 0.05). False Positive (FP) scores decreased for both the control and intervention group (p 0.05), this decrease was from 4.20 to 3.20 for the control group and from 5.87 to 3.27 for the intervention group. True Negative (TN) scores increased, from 5.13 to 6.73 for the intervention group (p 0.05). Mean decision time decreased for both the control and intervention group.The tool led to positive effects on participant performance and could be a useful aid in chest image interpretation learning.Improvements in performance were observed with a digital tool. The tool could improve image interpretation methods and training.

IntroductionAbortion became decriminalised in Northern Ireland in October 2019. Until that point there existed no evidence concerning the views of health professionals on decriminalisation or on their willingness to be involved in abortion care. The purpose of this study was to address this lack of evidence, including all categories of health professionals working in obstetrics and gynaecology units in Northern Ireland.MethodsThe online survey was targeted at medical, nursing and midwifery staff working in the obstetrics and gynaecology units in each Health and Social Care (HSC) Trust in Northern Ireland. The survey was issued via clinical directors in each Trust using the REDCap platform.ResultsThe findings showed widespread support for decriminalisation of abortion up until 24 weeks’ gestation (n=169, 54%). The majority of clinicians stated they were willing to provide abortions in certain circumstances (which were undefined) (n=188, 60% medical abortions; n=157, 50% surgical abortions). Despite regional variation, the results show that there are sufficient numbers of clinicians to provide a service within each HSC Trust. The results indicate that many clinicians who report a religious affiliation are also supportive of decriminalisation (n=46, 51% Catholic; n=53, 45% Protestant) and are willing to provide care, countering the assumption that those of faith would all raise conscientious objections to service provision.ConclusionsThe findings of this study are very encouraging for the development, implementation and delivery of local abortion care within HSC Trusts in Northern Ireland and should be of value in informing commissioners and providers about the design of a service model and its underpinning training programmes.

The article by Moser et al. details the outcomes of 11 patients with inflammatory bowel disease (IBD) as the main manifestation of their immune deficiency syndrome who are treated with allogeneic transplantation. The authors report low rates of complications (including graft-versus-host disease) and resolution of symptoms. Here we outline whether allogeneic transplantation should be considered more broadly for IBD. Commentary on: Moser et al. Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation. Br J Haematol 2022 (Online ahead of print). doi:10.1111/bjh.18497.

Large scale, high pressure ratio (PR) centrifugal compressors are commonly made up of a radial impeller with a vaned diffuser. In research to date, the majority of research and design has focused on extending the operating range or improving the compressor efficiency. However, a cost and weight saving can be achieved by reducing the compressor dimensions. This is a study of a vaned diffuser design concept aiming to reduce the overall radial dimensions of the compressor without any sacrifice of compressor performance at design point (DP).The study parameterized a diverging endwall diffuser concept and optimized it to achieve a similar performance within a reduced radial outlet dimension. A metamodel assisted Multi Objective Genetic Algorithm (MOGA) method has been used. A numerical approach has been used to investigate how the flow physics within the diffuser passage changed with the new geometry and detailed experimental measurements have been used to validate the numerical approach. The result of this study is a summary of the impact of vane geometry defining parameters within a diverging endwall concept which offers design guidance for application of the concept. The measured performance showed that the same efficiency performance was achieved within a 15% radially reduced diffuser passage using the diverging endwall concept.

Often, an improvement in performance at one operating point in a compressor/turbine operating map will lead to a reduction in performance at another area. For example, improving the efficiency of a compressor at design point (DP) may result in a reduction of efficiency at other operating points or it may result in a reduced stable operating range. In order to reduce the compressor cost and weight, a 15% radial reduction was applied to the diffuser passage length of a high pressure ratio centrifugal compressor. The diffuser endwall was diverged to achieve an appropriate area ratio from diffuser inlet to outlet. Two different vane shapes were considered with the radially reduced diffuser passage. The first diffuser vane was a scaled version of the baseline airfoil vane shape and this was used to develop an understanding of the impact of the passage length reduction and diverging endwall. The second vane geometry was parameterized using an unconventional method derived from published literature and optimized to improve performance at DP. Increased losses were generated through the diffuser passages of the radially reduced designs, but this was compensated for by lower losses through the volute due to more desirable flow at volute inlet. As a result, the radially reduced designs not only matched the performance of the baseline configuration, but also succeeded in achieving a marginal efficiency improvement. Furthermore, despite not being one of the goals of the optimization procedure, an extension of the stable operating range of 36% and 20% at the highest speed condition was achieved for the scaled and optimized designs, respectively. The current study focuses on understanding the physical reasons that generated this significant enhancement to the compressor operating range. In order to acquire the desired understanding, experimental data is presented to validate the Computational Fluid Dynamics (CFD) model and a detailed numerical investigation is presented to explain the changes in the flow field within the radially reduced designs. The study focuses on low flow rate operating points, necessitating the use of an Unsteady Reynolds Averaged Navier-Stokes (URANS) approach to analyse the flow. Detailed scrutiny of the flow field revealed a secondary flow feature in the diffuser passage which resulted in higher diffuser passage losses at DP but stabilised the flow as it developed for lower mass flow rate operating points.

OBJECTIVE Half of US children with autism spectrum disorder (ASD) have attempted to elope from adult supervision at least once, elevating their risk for serious injury/death. This study aimed to assess, in a sample of children with ASD aged 4 to 18 years who had previously wandered, whether electronic tracking device (ETD) use is associated with changes in the elopement behavior and household quality of life (QOL). METHODS An anonymous, online questionnaire assessing elopement interventions, elopement behavior, household QOL, attitudes toward ETDs, and sociodemographics was distributed via US autism-related organizations to caregivers of children with ASD. Differences in retrospective estimates of elopement behavior and household QOL before ETD use and during ETD use were evaluated using Wilcoxon signed-rank tests. RESULTS A total of 2563 participants completed the questionnaire; 1459 participants met the inclusion criteria. For the current (n = 361) and past (n = 96) ETD users, ETD use was associated with decreased frequency and duration of elopement and decreased risk for serious injury because of elopement (all p < 0.001). ETD use was similarly associated with improvements across all 5 measures of QOL. Among the past ETD users, reasons for discontinuation included device discomfort/fit (33.3%), burden of use (27.1%), and financial cost (14.6%). Among the non-ETD users (n = 1002), common barriers to ETD use were cost (47.5%) and lack of awareness of ETD technology (18.8%). CONCLUSION Electronic tracking devices represent a promising technology to help safeguard the well-being of children with ASD while reducing the emotional toll that elopement imposes on families. Cost concerns, burden of use, and lack of awareness seem to limit the widespread adoption of ETDs.

Key messages The 1967 Abortion Act establishing legal abortion in the rest of the UK has never applied in Northern Ireland (NI). With few exceptions, abortion has remained illegal and unavailable. Women have had to travel to Great Britain, funding treatment themselves until 2017 when the UK Department of Health and Social Care agreed to fund abortions provided by the main UK private abortion providers via a Central Booking System. Abortion was decriminalised in NI on 22 October 2019 under the Northern Ireland (Executive Formation etc) Act 2019.1 Regulations have been introduced; however, services have yet to be commissioned. The legal framework, The Abortion (Northern Ireland) (No. 2) Regulations 2020,2 came into effect on 31 March 2020 just after UK lockdown due to the COVID-19 pandemic, ‘stay home’ advice and the introduction of travel restrictions within the UK. Flights were cancelled, meaning accessing abortion in England involved an 8-hour ferry trip each way. Two women attempted suicide after flights were cancelled and they were unable to travel. Accessing abortion was problematic despite it being recognised as an essential service during the pandemic by the Faculty of Sexual & Reproductive Healthcare (FSRH)3 and the Royal College of Obstetricians & Gynaecologists (RCOG). Abortion is decriminalised and allowed without …

Preservice teachers need experiences that prepare them to work in a variety of settings with a diverse population. Teacher education programs work with mentor teachers and partner schools to provide preservice teachers with time to practice cultural responsiveness. Reflection can be used to explore and discuss these experiences. This chapter will include information on preparing culturally responsive educators with the use of advocacy and reflection, early hands-on experiences, and collaborative professional development. The study involved mentor teachers who reflected on the cultural responsiveness of students placed in their classroom. Preservice teachers completed a survey reflecting on their cultural responsiveness. Preservice teachers need opportunities to work in diverse settings with mentor teachers who support them through the process, and then opportunities to reflect on experiences. The feedback loop between teacher education programs, preservice and mentor teachers is a critical component to successfully preparing culturally responsive teachers.

The aim of this study was to develop and test a new classification scale to describe looking behaviours (gaze fixations and gaze shifts) in relation to eye-pointing. The Eye-pointing Classification Scale (EpCS) was developed and tested following established procedures for the construction and evaluation of equivalent scales, and involved 2 phases: Drawing on research literature, Phase 1 involved initial drafting of the scale through a series of multi-disciplinary group discussions; evaluation of the scale through a survey procedure, and subsequent expert group evaluation. Phase 2, was an examination of scale reliability and relationships between child characteristics and level of EpCS classification. In Phase 1, an initial draft of the scale was developed and then evaluated by 52 participants in 10 countries, leading to its refinement. Subsequent expert evaluation of content, style and structure indicated that no further refinement was required. In Phase 2, the scale achieved excellent levels of reliability in clinical testing. A significant relationship was identified between level of child motor ability and EpCS classification, and level of child language understanding and EpCS classification.Implications for rehabilitationNon-speaking children with severe bilateral cerebral palsy who have limited upper limb movement may communicate by using controlled looking behaviours to point to objects and people, referred to as eye-pointing.However, there is little consensus as to which looking behaviours represent eye-pointing and which do not.The Eye-pointing Classification Scale (EpCS) was developed to describe looking behaviours related to eye-pointing in this population of childrenThe EpCS provides a new robust tool for clinical management and research with children with cerebral palsy. Non-speaking children with severe bilateral cerebral palsy who have limited upper limb movement may communicate by using controlled looking behaviours to point to objects and people, referred to as eye-pointing. However, there is little consensus as to which looking behaviours represent eye-pointing and which do not. The Eye-pointing Classification Scale (EpCS) was developed to describe looking behaviours related to eye-pointing in this population of children The EpCS provides a new robust tool for clinical management and research with children with cerebral palsy.

RituxiCAN-C4 combined an open-labeled randomized controlled trial (RCT) in 7 UK centers to assess whether rituximab could stabilize kidney function in patients with chronic rejection, with an exploratory analysis of how B cell-depletion influenced T cell anti-donor responses relative to outcome. Between January 2007 and March 2015, 59 recruits were enrolled after screening, 23 of whom consented to the embedded RCT. Recruitment was halted when in a pre-specified per protocol interim analysis, the RCT was discovered to be significantly underpowered. This report therefore focuses on the exploratory analysis, in which we confirmed that when B cells promoted CD4+ anti-donor IFNγ production assessed by ELISPOT, this associated with inferior clinical outcome; these patterns were inhibited by optimized immunosuppression but not rituximab. B cell suppression of IFNγ production, which associated with number of transitional B cells and correlated with slower declines in kidney function was abolished by rituximab, which depleted transitional B cells for prolonged periods. We conclude that in this patient population, optimized immunosuppression but not rituximab promotes anti-donor alloresponses associated with favorable outcomes. Clinical Trial Registration: Registered with EudraCT (2006-002330-38) and www.ClinicalTrials.gov, identifier: NCT00476164.

Objectives This systematic review aimed to determine the strength of evidence available in the literature on the effect of training to develop the skills required by radiographers to interpret plain radiography chest images. Key findings Thirteen articles feature within the review. Sample size varied from one reporting radiographer to 148 radiography students/experienced radiographers. The quality of the articles achieved a mean score of 7.5/10, indicating the evidence is strong and the quality of studies in this field is high. Investigative approaches included audit of participants' performance in clinical practice post formal training, evaluation of informal training and the impact of short feedback sessions on performance. Conclusion All studies demonstrated positive attributions on user performance. Using a combination of training techniques can help maximise learning and accommodate those with different preferred learning types.

This study assessed pediatric residents’ reported knowledge of and self-confidence in identifying/treating 8 vaccine-preventable diseases. Pediatric residents nationwide (n = 385) reported (1) if they had previously diagnosed measles, mumps, rubella, diphtheria, tetanus, pertussis, varicella, and/or polio; (2) their comfort level in treating these diseases; (3) the likelihood of identifying symptoms; and (4) 16 disease-related statements as true/false. More than 25% of residents were not comfortable treating 5 of the 8 diseases. More than 25% reported themselves as unlikely/extremely unlikely to identify symptoms of 3 of these diseases. Third- or fourth-year residents did not feel more confident in identifying disease symptoms than first-year residents, except for pertussis ( P ≤ .01). True/false statement accuracy ranged from 56.8% correct (polio) to 94.6% correct (pertussis). Most residents (73.3%) were “extremely concerned” regarding parental vaccine refusal, and 96.0% felt that they would benefit from receiving more information. Increased emphasis on this subject in residency education is essential for the management of potential disease outbreaks.

This study presents performance specifications of an in-house developed human leukocyte antigen (HLA) typing assay using next-generation sequencing (NGS) on the Illumina MiSeq platform. A total of 253 samples, previously characterized for HLA-A, -B, -C, -DRB1 and -DQB1 were included in this study, which were typed at high-resolution using a combination of Sanger sequencing, sequence-specific primer (SSP) and sequence-specific oligonucleotide probe (SSOP) technologies and recorded at the two-field level. Samples were selected with alleles that cover a high percentage of HLA specificities in each of five different race/ethnic groups: European, African-American, Asian Pacific Islander, Hispanic and Native American. Sequencing data were analyzed by two software programs, Omixon's target and GenDx's NGSengine. A number of metrics including allele balance, sensitivity, specificity, precision, accuracy and remaining ambiguity were assessed. Data analyzed by the two software systems are shown independently. The majority of alleles were identical in the exonic sequences (third field) with both programs for HLA-A, -B, -C and -DQB1 in 97.7% of allele determinations. Among the remaining discrepant genotype calls at least one of the analysis programs agreed with the reference typing. Upon additional manual analysis 100% of the 2530 alleles were concordant with the reference HLA genotypes; the remaining ambiguities did not exceed 0.8%. The results demonstrate the feasibility and significant benefit of HLA typing by NGS as this technology is highly accurate, eliminates virtually all ambiguities, provides complete sequencing information for the length of the HLA gene and forms the basis for utilizing a single methodology for HLA typing in the immunogenetics labs.