Exploring aspects of the cognitive behavioural model of physical hoarding in relation to digital hoarding behaviours.

While the hoarding of physical objects has been extensively explored, there is little research relating to the hoarding of digital materials. The research that has been conducted suggests that digital hoarding (DH) behaviours appear to have some similarities with physical hoarding (PH) behaviours, and can be just as psychologically distressing. This study uses the framework of the cognitive behavioural model of PH to explore DH behaviours, including possible similarities regarding emotional attachment to digital possessions, and possible links with Obsessive Compulsive Disorder (OCD) and indecisiveness.

Characterising and justifying sample size sufficiency in interview-based studies: systematic analysis of qualitative health research over a 15-year period.

Background: Choosing a suitable sample size in qualitative research is an area of conceptual debate and practical uncertainty. That sample size principles, guidelines and tools have been developed to enable researchers to set, and justify the acceptability of, their sample size is an indication that the issue constitutes an important marker of the quality of qualitative research. Nevertheless, research shows that sample size sufficiency reporting is often poor, if not absent, across a range of disciplinary fields.

An International Standard for holotranscobalamin (holoTC): international collaborative study to assign a holoTC value to the International Standard for vitamin B12 and serum folate.

Background: Investigation of possible B12 and folate deficiencies requires measurement of these vitamins in serum. There is evidence that holotranscobalamin (holoTC), the active portion of B12 available to cells, is a more specific marker of early B12 deficiency than total B12. The availability of immunoassays for holoTC prompted an international collaborative study to assign a holoTC value to the World Health Organization (WHO) 1st International Standard (IS) for vitamin B12 and serum folate, 03/178.

Specifications for anti-A and anti-B in intravenous immunoglobulin: history and rationale.

Intravenous immunoglobulin (IVIG) products are generally safe and efficacious, although treatment-related adverse reactions can occur in recipients. Adverse reactions include hemolysis in non-blood group O recipients linked to the passive transfer of anti-A and/or anti-B present in the fractionated immunoglobulin product. In light of the recent increase in reported cases of severe hemolysis associated with anti-A and/or anti-B, this article traces the development of pharmacopoeial specifications, tests, and reference reagents to control their titers in IVIG products.

An autologous endothelial cell:peripheral blood mononuclear cell assay that detects cytokine storm responses to biologics.

There is an urgent unmet need for human tissue bioassays to predict cytokine storm responses to biologics. Current bioassays that detect cytokine storm responses in vitro rely on endothelial cells, usually from umbilical veins or cell lines, cocultured with freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy adult volunteers. These assays therefore comprise cells from 2 separate donors and carry the disadvantage of mismatched tissues and lack the advantage of personalized medicine.

The 3rd International Standard for serum IgE: international collaborative study to evaluate a candidate preparation.

Background: The measurement of serum IgE aids in the diagnosis and management of atopic allergic disease and hyper-IgE immunodeficiency syndromes. The 2nd World Health Organization (WHO) International Reference Reagent (IRR) for serum IgE (75/502; 5000 IU/ampoule), is widely used to calibrate assays for serum IgE. Exhaustion of stocks of the 2nd IRR necessitated the production of a replacement preparation and its evaluation in an international collaborative study to determine its suitability to serve as the 3rd International Standard (IS) for serum IgE.

Priming moral self-ambivalence heightens deliberative behaviour in self-ambivalent individuals.

Background: Recent work on cognitive-behavioural models of obsessive-compulsive disorder has focused on the roles played by various aspects of self-perception. In particular, moral self-ambivalence has been found to be associated with obsessive-compulsive phenomena.

Aims: In this study we used an experimental task to investigate whether artificially priming moral self-ambivalence would increase participants' deliberation on ethical problems, an index that might be analogous to obsessive-compulsive behaviour.

Severity of the TGN1412 trial disaster cytokine storm correlated with IL-2 release.

Aim: To determine if cytokine release with a solid phase assay is predictive of adverse responses for a range of therapeutic mAbs.

Methods: Cytokine ELISAs and a multi-array system were used to compare responses generated by different therapeutic mAbs using a solid phase assay. Flow cytometry was employed to determine the cellular source of those cytokines.

Antibody C region influences TGN1412-like functional activity in vitro.

The unexpected outcome of the clinical trial of the superagonistic CD28 mAb TGN1412 (IgG4κ) continues to stimulate interest. We show that TGN1412 binds similarly to human and cynomolgus macaque FcγR, eliminating the possibility that differences in Fc-mediated interactions with FcγR contributed to the failure of preclinical testing in macaques to predict toxicity in humans. The influence of the Fc domain and C region structure on the in vitro functional activity of TGN1412 was investigated using F(ab')(2) and Fab fragments derived from TGN1412 recovered from the trial and recombinant TGN1412 subclass variants and mutants.

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary.

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES--serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)--and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES.

Biomarkers of folate status in NHANES: a roundtable summary.

A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged ≥60 y are available in NHANES 1999-2002.

Consistent manufacturing and quality control of a highly complex recombinant polyclonal antibody product for human therapeutic use.

The beneficial effect of antibody therapy in human disease has become well established mainly for the treatment of cancer and immunological disorders. The inherent monospecificity of mAbs present limitations to mAb therapy which have become apparent notably in addressing complex entities like infectious agents or heterogenic endogenous targets. For such indications mixtures of antibodies comprising a combination of specificities would convey more potent biological effect which could translate into therapeutic efficacy.

Endothelial cells co-stimulate peripheral blood mononuclear cell responses to monoclonal antibody TGN1412 in culture.

The failure of preclinical testing to predict the severity of the cytokine storm experienced by the recipients of the superagonistic anti-CD28 monoclonal antibody (mAb) TGN1412 during its Phase 1 clinical trial prompted the development of new in vitro experimental approaches for mimicking in vivo cytokine release and lymphoproliferation. Peripheral blood mononuclear cells (PBMC) presented to TGN1412 immobilised on plastic has previously been shown to stimulate a pro-inflammatory cytokine response. The aim of the present study was to investigate a 'co-culture' model for the detection of TGN1412-like immunomodulatory activity in which TGN1412 was presented to PBMC in the presence of monolayers of endothelium-derived cells and other cell types, followed by measurement of cytokine levels in the culture supernatants and proliferation of PBMC.

The mediating roles of disgust sensitivity and danger expectancy in relation to hand washing behaviour.

Background: Recent interest in the role of vulnerability factors in obsessional washing has suggested that disgust sensitivity, danger expectancy and health anxiety may be of interest.

Aims: This study explores the differential impact of these factors on both behavioural and cognitive measures of washing behaviour and is based on a replication of the Jones and Menzies (1997) experiment, during which participants immersed their hands in a noxious compound while rating themselves on a range of measures: the time they subsequently took to wash their hands was measured and danger expectancies were found to be the best predictor of this.

Method: The present study added measures of disgust sensitivity and health anxiety to this experimental methodology while removing factors they found to be of little import to compulsive washing.

Release of proteolytic activity following reduction in therapeutic human serum albumin containing products: detection with a new neoepitope endopeptidase immunoassay.

Botulinum type A toxin (BoNT/A) is defined by its specific endopeptidase cleavage of SNAP25 between Gln(197) and Arg(198) under reducing conditions. The neurotoxin is widely used for therapeutic or cosmetic purposes, but should not contain other toxin serotypes or unwanted protease activities. Using a neoepitope endopeptidase immunoassay, additional cleavage between Arg(198) and Ala(199) was detected with a range of therapeutic BoNT/A products confirming an earlier report of an unidentified proteolytic component.

A WHO reference reagent for the Serum Transferrin Receptor (sTfR): international collaborative study to evaluate a recombinant soluble transferrin receptor preparation.

Background: The usefulness of serum transferrin receptor (sTfR) as a marker of iron deficiency is limited by lack of standardization of commercial immunoassays for sTfR. An international collaborative study was performed to evaluate a lyophilized preparation of recombinant soluble transferrin receptor (rsTfR) for its suitability to serve as a World Health Organization (WHO) Reference Reagent to standardize immunoassays for sTfR.

Methods: The concentration of pure rsTfR was determined from the A(280 nm) using the adjusted theoretical extinction coefficient and molecular weight calculated from its sequence, before dilution and lyophilization in a sTfR-depleted serum matrix.

The development and role of international biological reference materials in the diagnosis of anaemia.

Anaemia is a major global health problem. Although the main cause is iron deficiency, anaemia also results from other nutritional deficiencies (folate and vitamin B12), haemolytic disorders including haemoglobinopathies, and bone marrow disorders. Accurate diagnosis of anaemia is dependent on reliable diagnostic tests and reference ranges, which in turn are dependent on effective standardisation.

Negative perfectionism increases the risk of fatigue following a period of stress.

Cognitive-behavioural models of excessive fatigue suggest that people who believe that failure to meet high standards indicates unacceptability to others (a form of 'negative perfectionism') are at risk of fatigue after a period of illness or stress. The present study investigates this using a prospective design and possible mediating factors between such beliefs and fatigue were also investigated. Undergraduate students completed questionnaires at the beginning of the academic year (time 1; n = 436) and again following a time of academic pressure, 16 weeks later (time 2; n = 206).

Therapeutic IgG4 antibodies engage in Fab-arm exchange with endogenous human IgG4 in vivo.

Two humanized IgG4 antibodies, natalizumab and gemtuzumab, are approved for human use, and several others, like TGN1412, are or have been in clinical development. Although IgG4 antibodies can dynamically exchange half-molecules, Fab-arm exchange with therapeutic antibodies has not been demonstrated in humans. Here, we show that natalizumab exchanges Fab arms with endogenous human IgG4 in natalizumab-treated individuals.

Automated immunoassay methods for ferritin: recovery studies to assess traceability to an international standard.

Background: Ferritin standardisation is problematical due to the heterogeneity of ferritin isoforms and the antibodies used in its immunoassay, and the lack of a reference measurement procedure. We investigated the performance of the 1st (liver), 2nd (spleen) and 3rd (recombinant) International Standards (ISs) for ferritin in major assays.

Methods: The ferritin in a serum pool 'spiked' with either the 2nd or 3rd IS for ferritin was measured by 52 laboratories using five automated methods and the recovery of the target values calculated.

Claustrophobia in MRI: the role of cognitions.

Purpose: This study aimed to investigate the role of cognitive and behavioural factors in the experience of claustrophobia in the context of magnetic resonance imaging (MRI) scanners.

Materials And Methods: One hundred and thirty outpatients attending an MRI unit completed questionnaires before and after their scans. Specific measures of experience in the scanner included subjective anxiety, panic symptoms, strategies used to stay calm and negative cognitions (such as 'I will suffocate' and 'I am going to faint in here').

Anti-D and anti-i activities are inseparable in V4-34-encoded monoclonal anti-D: the same framework 1 residues are required for both reactivities.

Background: The heavy-chain V4-34 germline gene segment is mandatory for pathologic cold-reacting autoantibodies with anti-I/i specificity (cold agglutinins) and is also preferentially used by monoclonal immunoglobulin M alloantibodies against D and other Rh antigens. The use of the V4-34 segment by monoclonal anti-D has previously been shown to also confer anti-I/i reactivity (cold agglutinin activity), which has implications for the use of such antibodies for Rh blood typing. V4-34 framework 1 (FR1) sequence is believed to be critical for cold agglutinin activity of cold agglutinins.

Varicella and the pregnant woman: prevention and management.

Infection with varicella zoster virus (VZV) is often considered a childhood 'right of passage'; however, primary infection occurring in women of child-bearing age can have significant adverse consequences both for the mother and for her fetus. During the first trimester, primary VZV infection may result in stillbirth or a baby born with the stigmata of the congenital varicella syndrome, while infection in the peripartum period can result in neonatal varicella, which carries a significant mortality rate despite appropriate antiviral therapy. Varicella in pregnant women can progress to pneumonitis and other severe sequelae that may also compromise the viability of the fetus.