Practitioners' ability to remotely develop understanding for personalised care and support planning: a thematic analysis of multiple data sources from the feasibility phase of the Dementia Personalised Care Team (D-PACT) intervention.

Practitioner understanding of patients' preferences, wishes and needs is essential for personalised health care i.e., focusing on 'what matters' to people based on their individual life situation. To develop such an understanding, dementia practitioners need to use communication practices that help people share their experiences, preferences, and priorities. Following the COVID-19 pandemic, dementia support is likely to continue to be delivered both remotely and in-person. This study analysed multiple sources of qualitative data to examine the views of practitioners, people living with dementia and carers, and researchers on how an understanding of what matters to people living with dementia can be developed remotely via telephone and video call. Access to environmental stimuli, the remote use of visual tools, peoples' tendency to downplay or omit details about their troubles and carers' ability to disclose privately were interpreted, through thematic analysis, to be factors affecting how practitioners sought to develop understanding remotely. Cumulatively, findings show that while remote support created unique challenges to practitioners' ability to develop understanding for personalised care, practitioners developed adaptive strategies to overcome some of these challenges. Further research should examine how, when and for whom these adapted practices for remote personalised care work, informing the development of evidence-based guidance and training on how practitioners can remotely develop the understanding required for personalised care.

How has contraceptive provision at Family Planning clinics in Aotearoa New Zealand changed between 2009, 2014 and 2019: a cross-sectional analysis.

AIM: To investigate changes in contraceptive starts among Family Planning clients in 2009, 2014 and 2019. METHODS: National data of 75,825 contraceptive starts of clients at Family Planning clinics in New Zealand in 2009, 2014 and 2019 were analysed to measure changes in contraceptive starts across the three points in time. Data were analysed by age and ethnicity at each point in time, and by deprivation in 2019. RESULTS: After being adjusted for age and ethnicity, there was a significant decline in the proportion of starts for the combined oral contraceptive pill (43% to 23%), the progestogen-only pill (22% to 13%) and Depo Provera (15% to 12%) from 2009 to 2019. There was a significant increase in the proportion of starts for implants (0.7% to 22%) and intra-uterine contraception (19% to 30%). There were significant differences in contraceptive starts between ethnicities and levels of deprivation. CONCLUSIONS: There was an overarching trend of increasing long-acting reversible contraceptive (LARC) starts from 2009 to 2019 among Family Planning clients across all age groups and ethnicities. There were also differences in the types of contraceptive starts by ethnicity and deprivation. Information about contraceptive use and changes over time, by age and ethnicity, is essential for evidence-based policy, funding decisions and ensuring equitable access to contraception.

Detection of Shiga toxin-producing Escherichia coli (STEC) in beef products using droplet digital PCR.

Many of the current accredited methods for the molecular detection of Shiga toxin-producing Escherichia coli (STEC) in foods rely on a PCR-based screen for the pathotype-specific genetic markers stx and eae. Unfortunately, these methods can inaccurately conclude the presence of E.coli containing both stx and eae because of the inability of the methods to determine if the two genes originated from a single organism as opposed to a mixture of organisms. This study was undertaken to evaluate if a droplet digital PCR (ddPCR)-based method that does not require DNA isolation could reliably identify the presence of an STEC containing eae in beef samples by confirming that both genes reside within the same cell, even when present in a mixed culture. The ddPCR system used in this study, dd-Check STEC Solution (Bio-Rad), works without the need for DNA isolation by partitioning intact cells into emulsion droplets, where they are lysed, and subsequently undergo multiplexed endpoint PCR. This enables the assay to differentiate between samples where a single organism contains both stx and eae from samples in which stx and eae reside in different organisms. Comparisons were made between the dd-Check STEC Solution, the BAX System Real-Time PCR STEC assay suite (Hygiena), and the iQ-Check STEC PCR detection kit (Bio-Rad) using 37 unique simulations of E. coli contamination in ground beef. While no single platform was consistently superior at detecting eae and stx across all pathogens tested, the results indicated that the dd-Check STEC Solution has the potential to reduce the number of inaccurately identified samples when screening for E. coli with a stx+, eae+ genotype because it can identify the co-existence of multiple virulence genes within a cell even when in the presence of a mixed microbial population containing identical genes. Ultimately, incorporation of this system could result in substantial cost savings by reducing the expenses incurred when product samples are incorrectly classified as containing E. coli with a stx+, eae+ genotype.

Modification and Matrix Extension of the Bio-Rad iQ-Check E. coli O157:H7, STEC VirX, and STEC SerO Test Kits for the Detection of Shiga Toxin-Producing Escherichia coli (STEC) and Escherichia coli O157 From a Single Enrichment.

BACKGROUND: The iQ-Check Real-Time PCR kits use PCR technology based on gene amplification and detection by a real-time PCR thermalcycler for the detection of target analytes in select food matrices. The iQ-Check E. coli O157:H7 [Performance Tested MethodSM (PTM) 020801] and STEC VirX and STEC SerO (combined PTM 121203) methods were previously validated for different matrices under different enrichment schemes. OBJECTIVE: To modify the current iQ-Check E. coli O157:H7 Kit for the detection of Escherichia coli O157:H7 from 25 to 375 g for raw ground beef (17% fat), raw beef trim, and fresh spinach. In addition, a matrix extension was validated for iQ-Check E. coli O157:H7 for raw chicken breast without skin (25 g), raw chicken thigh with skin (25 g), mechanically separated chicken (25 g), and raw ground pork (25 g). The study also included the modification of the iQ-Check STEC VirX and SerO Kits for the detection of non-O157 Shiga toxin-producing E. coli (STEC) for raw ground beef (375 g), raw beef trim (375 g), and fresh spinach (375 g) from STEC Enrichment Broth to buffered peptone water (BPW). All tests were carried out at 8-22 h (10-22 h for fresh spinach). METHODS: Ground beef, beef trim, and spinach were co-inoculated with E. coli O157:H7, non-O157 STECs, and Salmonella spp. and analyzed for E. coli O157:H7 and non-O157 STECs after an 8-22 h enrichment in BPW for the beef matrices and after a 10-22 h enrichment in BPW for spinach. The chicken matrices were inoculated with E. coli O157:H7 only and analyzed after an 8-22 h enrichment in BPW. The iQ-Check Free DNA Removal Solution workflow was utilized for all matrices. Confirmations at the 22 h time point and method comparisons were conducted with the appropriate reference method as outlined in the U.S. Food and Drug Administration Bacteriological Analytical Manual Chapter 4A or the U.S. Department of Agriculture Food Safety and Inspection Service Microbiology Laboratory Guidebook Chapters 5.09 and 5B.05. For the iQ-Check STEC VirX and STEC SerO Kits, inclusivity and exclusivity were also performed. RESULTS: The two inclusivity and exclusivity evaluations indicated that the test methods can accurately detect the target analytes and correctly excluded nontarget organisms after 8 h of enrichment. In the method comparison study, the iQ-Check E. coli O157:H7 and STEC VirX and STEC SerO test kits demonstrated no statistically significant differences between candidate and reference method results or between presumptive and confirmed results for all food matrices analyzed and the two time points (8 or 10 and 22 h). Both time points produced the same results, with no discrepancies. CONCLUSIONS: The iQ-Check real-time PCR kits are effective methods for the detection of E. coli O157 and non-O157 STECs (both the virulence factors and the O groups) from raw ground beef, raw beef trim, and fresh spinach in 375 g samples enriched in BPW for 8-22 h (10-22 h for fresh spinach). In addition, the iQ-Check E. coli O157 Kit is effective in detecting E. coli O157 in 25 g samples of raw chicken breast without skin, raw chicken thigh with skin, mechanically separated chicken, and raw ground pork. The iQ-Check test kits allow the end user to pair enrichments for multiple target analytes, allowing the user to prepare a single enrichment and perform a single DNA extraction. The Free DNA Removal Solution removes free DNA from samples prior to PCR analysis, protecting DNA from intact and living cells. HIGHLIGHTS: The method modifications were granted based on the data collected.

Modification of the Bio-Rad iQ-Check Listeria spp. Kit for the Detection of Listeria Species in Environmental Surfaces.

BACKGROUND: The Bio-Rad iQ-Check Listeria spp. Kit uses real-time PCR technology for detection of Listeria species in select food matrixes and environmental surfaces. OBJECTIVE: The iQ-Check Listeria spp. method was modified to reduce the enrichment medium volume for environmental sponges from 225 and 100 to 60 mL and to reduce the enrichment time for sponges and swabs from 25 ± 1 to as short as 18 h. The modified method was validated with stainless steel, polystyrene plastic, and sealed concrete using sponges or swabs with two different neutralizing buffers (Letheen Broth and HiCap™ Neutralizing Broth). In addition, the Bio-Rad Free DNA Removal Solution was used for all environmental samples. METHODS: The iQ-Check Listeria spp. modified method was compared with the reference culture method in the U.S. Department of Agriculture Food Safety and Inspection Service Microbiology Laboratory Guidebook Chapter 8.10 using an unpaired study design. RESULTS: In the method comparison study, the iQ-Check Listeria spp. modified method demonstrated no statistical difference in performance between candidate and reference method results or between presumptive and confirmed results for all environmental surfaces analyzed using HiCap Neutralizing Broth (World Bioproducts LLC) and Letheen broth. CONCLUSIONS: The modified iQ-Check Listeria spp. method is an effective method for the detection of Listeria species in environmental surfaces using both types of neutralizing buffer. HIGHLIGHTS: The method modification was granted based on the data collected.

Retrospective Evaluation of Cycled Resin in Viral Clearance Studies-A Multiple Company Collaboration.

The BioPhorum Development Group Viral Clearance Workstream performed a collaborative retrospective analysis to evaluate packed bed chromatographic resin performance after repeated cycling for two commonly used chromatography steps in biopharmaceutical manufacturing: protein A and anion exchange. Key variables evaluated in the assessment included virus type, resin type, number of reuse cycles, and virus challenge. In this retrospective analysis of viral clearance data on naïve versus cycled resin, powered by the availability of a decade's worth of accumulated industry data, clearance capability was not negatively impacted by resin cycling. This finding is consistent with publications showing that surrogates for viral clearance capabilities could be employed in lieu of testing the viral clearance of cycled resins for protein A and anion exchange chromatography. The rigorous analysis of the retrospective data supports the view that viral clearance studies for cycled resins are not necessary provided that appropriate cleaning methods are applied during repeated use of the chromatography columns.LAY ABSTRACT: The manufacturing processes for biopharmaceutical products often include reusable chromatographic resins that remove process- and product-related impurities as well as potential contaminating viruses. Typically, chromatography resin is "cycled" through repeated steps of resin conditioning, product purification, and resin cleaning. The cycling approach has been evaluated in both small- and full-scale studies that show the performance parameters are maintained. The ability to remove virus is demonstrated separately in a focused small-scale virus-spiking study that is resource-intensive and costly. This paper is a retrospective review of industry data comparing virus removal by naïve and repeatedly cycled resins that summarizes the viral clearance impact of re-using protein A and anion exchange chromatography resins. The key variables evaluated in the assessment included virus type, resin type, number of cycles, and virus challenge. In this retrospective analysis, it was found that the viral clearance capability is not negatively impacted by resin cycling. This finding is consistent with other publications and supports the view that viral clearance studies for cycled resins are not necessary if appropriate cleaning methods are applied during the repeated use of the chromatography columns.Abbreviations: AAV-2, Adeno-associated virus; A-MuLV, Amphotropic murine leukemia virus; AEX, Anion-exchange chromatography; B/E, Bind and elute; BVDV, Bovine viral diarrhea virus; C.P.G., Controlled pore glass; DEAE, Diethylaminoethanol; EMCV, Encephalomyocarditis virus; FT, Flow through; HAV, Hepatitis A virus; HSV-1, Herpes simplex virus type 1; LOD, Limit of detection; LOQ, Limit of quantification; LRF, Log10 reduction factor; mAb, Monoclonal antibody; MVM, Minute virus of mice; NaOH, Sodium hydroxide; PA, Protein A; PPV, Porcine parvovirus; QA, Quaternary amine; QP, Quaternized polyethyleneimine; qPCR, Quantitative polymerase chain reaction; Reo3, Reovirus type 3; SuHV-1, Suid herpesvirus; SV40, Simian virus 40; X-MuLV, Xenotropic murine leukemia virus.

Reduced FcRn-mediated transcytosis of IgG2 due to a missing Glycine in its lower hinge.

Neonatal Fc-receptor (FcRn), the major histocompatibility complex (MHC) class I-like Fc-receptor, transports immunoglobuline G (IgG) across cell layers, extending IgG half-life in circulation and providing newborns with humoral immunity. IgG1 and IgG2 have similar half-lives, yet IgG2 displays lower foetal than maternal concentration at term, despite all known FcRn binding residues being preserved between IgG1 and IgG2. We investigated FcRn mediated transcytosis of VH-matched IgG1 and IgG2 and mutated variants thereof lacking Fc-gamma receptor (FcγR) binding in human cells expressing FcRn. We observed that FcγR binding was not required for transport and that FcRn transported less IgG2 than IgG1. Transport of IgG1 with a shortened lower hinge (ΔGly236, absent in germline IgG2), was reduced to levels equivalent to IgG2. Conversely, transport of IgG2 + Gly236 was increased to IgG1 levels. Gly236 is not a contact residue between IgG and FcRn, suggesting that its absence leads to an altered conformation of IgG, possibly due to a less flexible Fab, positioned closer to the Fc portion. This may sterically hinder FcRn binding and transport. We conclude that the lack of Gly236 is sufficient to explain the reduced FcRn-mediated IgG2 transcytosis and accounts for the low maternal/fetal IgG2 ratio at term.

Evaluation of the iQ-Check®Salmonella II Assay in Select Foods: Collaborative Study, First Action 2017.06.

The iQ-Check Salmonella II Real-Time PCR test kit utilizes Salmonella-specific oligonucleotide probes and primers for the rapid and specific detection of Salmonella species in select food types. The alternative method was evaluated by using 375 g test portions in an unpaired study design for two matrices, milk chocolate and dry dog food. Each matrix was compared with the U.S. Food and Drug Administration Chapter 5 Salmonella reference method. Fourteen technicians from 12 laboratories, including academia and industry, located within the United States and Canada participated in the collaborative study. Three levels of contamination were evaluated for each matrix: an uninoculated control level (0 CFU/test portion), a low inoculum level (0.2-2 CFU/test portion), and a high inoculum level (2-5 CFU/test portion). The statistical analysis was conducted according to the Probability of Detection (POD) statistical model. The results obtained for the low inoculum level test portions produced a difference in the candidate presumptive and confirmatory results (dLPOD) value with a 95% confidence interval of -0.05, (-0.15, 0.06) for the milk chocolate and 0.10, (-0.01, 0.21) for the dry dog food. The dLPOD results indicate an equivalence between the candidate method and reference method for the matrices evaluated, and the method demonstrated acceptable interlaboratory reproducibility as determined in the collaborative evaluation. False positive and false negative rates were determined for each matrix and produce values of <2%. Based on the data generated, the method demonstrated acceptable interlaboratory reproducibility data and statistical analysis.

When monoclonal antibodies are not monospecific: Hybridomas frequently express additional functional variable regions.

Monoclonal antibodies are commonly assumed to be monospecific, but anecdotal studies have reported genetic diversity in antibody heavy chain and light chain genes found within individual hybridomas. As the prevalence of such diversity has never been explored, we analyzed 185 random hybridomas, in a large multicenter dataset. The hybridomas analyzed were not biased towards those with cloning difficulties or known to have additional chains. Of the hybridomas we evaluated, 126 (68.1%) contained no additional productive chains, while the remaining 59 (31.9%) contained one or more additional productive heavy or light chains. The expression of additional chains degraded properties of the antibodies, including specificity, binding signal and/or signal-to-noise ratio, as determined by enzyme-linked immunosorbent assay and immunohistochemistry. The most abundant mRNA transcripts found in a hybridoma cell line did not necessarily encode the antibody chains providing the correct specificity. Consequently, when cloning antibody genes, functional validation of all possible VH and VL combinations is required to identify those with the highest affinity and lowest cross-reactivity. These findings, reflecting the current state of hybridomas used in research, reiterate the importance of using sequence-defined recombinant antibodies for research or diagnostic use.

Detection of transmissible viral proventriculitis and chicken proventricular necrosis virus in the UK.

Increasing evidence suggests that a new birnavirus, named chicken proventricular necrosis virus (CPNV), is the aetiological agent of transmissible viral proventriculitis (TVP). The present work aimed to explore the possible presence of both TVP and CPNV in the UK. Forty-four chickens showing TVP-compatible gross lesions were classified into three groups based on the histological lesions: (i) TVP-affected chickens: lymphocytic infiltration and glandular necrosis (n = 15); (ii) lymphocytic proventriculitis (LP)-affected chickens: lymphocytic infiltration without necrosis (n = 18); and (iii) without proventriculitis (WP): no lymphocytic infiltration or necrosis (n = 11). Nine proventriculi (seven out of 15 corresponding to TVP, and two out of 11 corresponding to LP) were positive for CPNV by reverse transcriptase polymerase chain reaction (RT-PCR). These results support the previously suggested idea of CPNV as causative agent of TVP. Moreover, these data show that CPNV can also be detected in a number of cases with LP, which do not fulfil the histological TVP criteria. Phylogenetic analysis of partial sequences of gene VP1 showed that British CPNV sequences were closer to other European CPNV sequences and might constitute a different lineage from the American CPNV. TVP cases with negative CPNV PCR results may be due to chronic stages of the disease or to the reduced PCR sensitivity on formalin-fixed paraffin-embedded tissues. However, involvement of other agents in some of the cases cannot totally be ruled out. As far as the authors are aware, this is the first peer-reviewed report of TVP as well as of CPNV in the UK, and the first exploratory CPNV phylogenetic study.

Retrospective Evaluation of Low-pH Viral Inactivation and Viral Filtration Data from a Multiple Company Collaboration.

Considerable resources are spent within the biopharmaceutical industry to perform viral clearance studies, which are conducted for widely used unit operations that are known to have robust and effective retrovirus clearance capability. The collaborative analysis from the members of the BioPhorum Development Group Viral Clearance Working Team considers two common virus reduction steps in biopharmaceutical processes: low-pH viral inactivation and viral filtration. Analysis included eight parameters for viral inactivation and nine for viral filtration. The extensive data set presented in this paper provides the industry with a reference point for establishing robust processes in addition to other protocols available in the literature (e.g., ASTM Std. E2888-12 for low-pH inactivation). In addition, it identifies points of weakness in the existing data set and instructs the design and interpretation of future studies. Included is an abundance of data that would have been difficult to generate individually but collectively will help support modular viral clearance claims.

Effects of Adult Romantic Attachment and Social Support on Resilience and Depression in Individuals with Spinal Cord Injuries.

BACKGROUND: Spinal cord injury (SCI) can cause psychological consequences that negatively affect quality of life. It is increasingly recognized that factors such as resilience and social support may produce a buffering effect and are associated with improved health outcomes. However the influence of adult attachment style on an individual's ability to utilize social support after SCI has not been examined. OBJECTIVE: The purpose of this study was to examine relationships between adult romantic attachment perceived social support depression and resilience in individuals with SCI. In addition we evaluated potential mediating effects of social support and adult attachment on resilience and depression. METHODS: Participants included 106 adults with SCI undergoing inpatient rehabilitation. Individuals completed measures of adult attachment (avoidance and anxiety) social support resilience and depression. Path analysis was performed to assess for presence of mediation effects. RESULTS: When accounting for the smaller sample size support was found for the model (comparative fit index = .927; chi square = 7.86, P = .01; ß = -0.25, standard error [SE] = -2.93, P < .05). The mediating effect of social support on the association between attachment avoidance and resilience was the only hypothesized mediating effect found to be significant (ß = -0.25, SE = -2.93, P < .05). CONCLUSIONS: Results suggest that individuals with SCI with higher levels of attachment avoidance have lower perceived social support which relates to lower perceived resilience. Assessing attachment patterns during inpatient rehabilitation may allow therapists to intervene to provide greater support.

Core outcome sets for use in effectiveness trials involving people with bipolar and schizophrenia in a community-based setting (PARTNERS2): study protocol for the development of two core outcome sets.

BACKGROUND: In the general population the prevalence of bipolar and schizophrenia is 0.24% and 1.4% respectively. People with schizophrenia and bipolar disorder have a significantly reduced life expectancy, increased rates of unemployment and a fear of stigma leading to reduced self-confidence. A core outcome set is a standardised collection of items that should be reported in all controlled trials within a research area. There are currently no core outcome sets available for use in effectiveness trials involving bipolar or schizophrenia service users managed in a community setting. METHODS: A three-step approach is to be used to concurrently develop two core outcome sets, one for bipolar and one for schizophrenia. First, a comprehensive list of outcomes will be compiled through qualitative research and systematic searching of trial databases. Focus groups and one-to-one interviews will be completed with service users, carers and healthcare professionals. Second, a Delphi study will be used to reduce the lists to a core set. The three-round Delphi study will ask service users to score the outcome list for relevance. In round two stakeholders will only see the results of their group, while in round three stakeholders will see the results of all stakeholder group by stakeholder group. Third, a consensus meeting with stakeholders will be used to confirm outcomes to be included in the core set. Following the development of the core set a systematic literature review of existing measures will allow recommendations for how the core outcomes should be measured and a stated preference survey will explore the strength of people's preferences and estimate weights for the outcomes that comprise the core set. DISCUSSION: A core outcome set represents the minimum measurement requirement for a research area. We aim to develop core outcome sets for use in research involving service users with schizophrenia or bipolar managed in a community setting. This will inform the wider PARTNERS2 study aims and objectives of developing an innovative primary care-based model of collaborative care for people with a diagnosis of bipolar or schizophrenia.

The effectiveness of personal budgets for people with mental health problems: a systematic review.

BACKGROUND: Personal budgets are a key policy priority in adult social care in England and are expected to become increasingly important in the care of adults with mental health problems. AIMS: This article systematically reviews evidence for the effectiveness of personal budgets for people with mental health problems across diverse outcomes. METHODS: The review, conducted in 2013, used the EPPI-Centre methodology for conducting a systematic review informed by Social Care Institute for Excellence guidelines. Data were extracted from studies and combined using meta-synthesis. RESULTS: Fifteen studies were included in the review which found mostly positive outcomes in terms of choice and control, quality of life, service use and cost-effectiveness. However, methodological limitations make these findings rather unreliable and insufficient to inform personal budgets policy and practice for mental health service users. CONCLUSIONS: Further high quality studies are required to inform policy and practice for mental health service users, which lags behind other adult social care groups in the use of personal budgets.

An investigation into IgE-facilitated allergen recognition and presentation by human dendritic cells.

BACKGROUND: Allergen recognition by dendritic cells (DCs) is a key event in the allergic cascade leading to production of IgE antibodies. C-type lectins, such as the mannose receptor and DC-SIGN, were recently shown to play an important role in the uptake of the house dust mite glycoallergen Der p 1 by DCs. In addition to mannose receptor (MR) and DC-SIGN the high and low affinity IgE receptors, namely FcεRI and FcεRII (CD23), respectively, have been shown to be involved in allergen uptake and presentation by DCs. OBJECTIVES: This study aims at understanding the extent to which IgE- and IgG-facilitated Der p 1 uptake by DCs influence T cell polarisation and in particular potential bias in favour of Th2. We have addressed this issue by using two chimaeric monoclonal antibodies produced in our laboratory and directed against a previously defined epitope on Der p 1, namely human IgE 2C7 and IgG1 2C7. RESULTS: Flow cytometry was used to establish the expression patterns of IgE (FcεRI and FcεRII) and IgG (FcγRI) receptors in relation to MR on DCs. The impact of FcεRI, FcεRII, FcγRI and mannose receptor mediated allergen uptake on Th1/Th2 cell differentiation was investigated using DC/T cell co-culture experiments. Myeloid DCs showed high levels of FcεRI and FcγRI expression, but low levels of CD23 and MR, and this has therefore enabled us to assess the role of IgE and IgG-facilitated allergen presentation in T cell polarisation with minimal interference by CD23 and MR. Our data demonstrate that DCs that have taken up Der p 1 via surface IgE support a Th2 response. However, no such effect was demonstrable via surface IgG. CONCLUSIONS: IgE bound to its high affinity receptor plays an important role in Der p 1 uptake and processing by peripheral blood DCs and in Th2 polarisation of T cells.

Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers.

Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal human platelet antigen-1a (HPA-1a), can result in intracranial hemorrhage and intrauterine death. We have developed a therapeutic human recombinant high-affinity HPA-1a antibody (B2G1Δnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fcγ receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1Δnab blocks monocyte chemiluminescence by >75%. In this first-in-man study, we demonstrate that HPA-1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1Δnab have the same intravascular survival as unsensitized platelets (190 hours), while platelets sensitized with a destructive immunoglobulin G1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1Δnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA-1a antibody) and B2G1Δnab survive 3 times as long in circulation compared with platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1Δnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunization in HPA-1a-negative mothers.

Magnetic bucket for rotating unmagnetized plasma.

A new experiment is described which generates flow in unmagnetized plasma. Confinement is provided by a cage of permanent magnets, arranged to form an axisymmetric, high-order, multipolar magnetic field. This field configuration-sometimes called a "magnetic bucket"-has a vanishingly small field in the core of the experiment. Toroidal rotation is driven by J × B forces applied in the magnetized edge. The cross-field current that is required for this forcing flows from anodes to thermionic cathodes, which are inserted between the magnet rings. The rotation at the edge reaches 3 km/s and is viscously coupled to the unmagnetized core plasma. We describe the conditions necessary for rotation, as well as a 0-dimensional power balance used to understand plasma confinement in the experiment.