Putting things right: An experimental investigation of memory biases related to symmetry, ordering and arranging behaviour.

BACKGROUND AND OBJECTIVES: Research indicates the presence of both explicit and implicit memory biases for threat. However, empirical support for the presence of memory biases related to symmetry, ordering and arranging is lacking, despite the fact that many individuals report anxiety associated with their personal belongings being out of place. The aim of this experiment was to examine memory biases for disorderliness and their associations with symmetry, ordering and arranging symptoms. METHODS: Eighty undergraduate participants were assigned to one of four conditions, consisting of rooms in which objects were arranged according to different levels of disorderliness (orderly, slightly disorderly, slightly orderly, and disorderly). Participants next completed a memory task in which their memory for disordered vs. ordered objects was assessed. Measures of OCD symptoms, preference for symmetry, OCD belief domains, anxiety and depression were completed. RESULTS: Analyses indicated that participants in the slightly disorderly condition showed significantly better recall and recognition for the disordered items than for the ordered items, and that those in the slightly orderly condition showed the same pattern in recall, but not recognition. No associations were found between a preference for symmetry and memory biases. LIMITATIONS: The sample scored particularly low on our measure of symptoms of preference for symmetry, compromising the generalizability of our results. CONCLUSIONS: Findings provide evidence for a general memory bias for disorderliness, although this bias does not appear to be associated with symmetry, ordering and arranging symptoms. Results are discussed from a cognitive-behavioural perspective with the consideration of feelings of incompleteness.

The Covert and Overt Reassurance Seeking Inventory (CORSI): Development, validation and psychometric analyses.

BACKGROUND: Reassurance seeking (RS) is motivated by perceived general and social/relational threats across disorders, yet is often under-recognized because it occurs in covert (i.e. subtle) and overt forms. Covert safety-seeking behaviour may maintain disorders by preventing corrective learning and is therefore important to identify effectively. AIMS: This study presents the validation and psychometric analyses of a novel measure of covert and overt, general and social/relational threat-related interpersonal RS. METHOD: An initial 30-item measure was administered to an undergraduate sample (N = 1626), as well as to samples of individuals diagnosed with obsessive compulsive disorder (OCD; n = 50), anxiety disorders (n = 60) and depression (n = 30). The data were subjected to exploratory and confirmatory factor analyses, and validation analyses. RESULTS: An exploratory factor analysis using principal axis factoring with oblique rotation yielded five interpretable factors, after removing four complex items. The resulting 26-item measure, the Covert and Overt Reassurance Seeking Inventory (CORSI), evidenced good convergent and divergent validity and accounted for 54.99% of the total variance after extraction. Factor correlations ranged from r = .268 to .736, suggesting that they may be tapping into unique facets of RS behaviour. In comparison with undergraduate participants, all clinical groups had significantly higher total scores [t (51.80-840) = 3.92-5.84, p < .001]. The CFA confirmed the five-factor model with good fit following the addition of four covariance terms (goodness of fit index = .897, comparative fit index = .918, Tucker-Lewis index = .907, root mean square error approximation = .061). CONCLUSION: The CORSI is a brief, yet comprehensive and psychometrically strong measure of problematic RS. With further validation, the CORSI has potential for use within clinical and research contexts.

High-dose chemotherapy plus autologous stem-cell transplantation as consolidation therapy in patients with relapsed multiple myeloma after previous autologous stem-cell transplantation (NCRI Myeloma X Relapse [Intensive trial]): a randomised, open-label, phase 3 trial.

BACKGROUND: Relapsed multiple myeloma has no standard treatment, and the role of autologous stem-cell transplantation (ASCT) has not been fully defined. We aimed to compare high-dose melphalan plus salvage ASCT with cyclophosphamide in patients with relapsed multiple myeloma who had previously undergone ASCT. METHODS: This multicentre, randomised, open-label, phase 3 study recruited patients aged at least 18 years with multiple myeloma who needed treatment for first progressive or relapsed disease at least 18 months after a previous ASCT from 51 centres across the UK. Before randomisation, eligible patients received bortezomib, doxorubicin, and dexamethasone (PAD) induction therapy and then underwent peripheral blood stem-cell mobilisation and harvesting if applicable. Eligible patients (with adequate stem-cell harvest) were randomly assigned (1:1), using an automated telephone randomisation line, to either high-dose melphalan 200 mg/m(2) plus salvage ASCT or oral cyclophosphamide (400mg/m(2) per week for 12 weeks). Randomisation was stratified by length of first remission or plateau and response to PAD re-induction therapy. The primary endpoint was time to disease progression, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00747877, and EudraCT, number 2006-005890-24. FINDINGS: Between April 16, 2008, and Nov 19, 2012, 297 patients were registered, of whom 293 received PAD re-induction therapy. Between Aug 26, 2008, and Nov 16, 2012, 174 patients with sufficient PBSCs were randomised to salvage ASCT (n=89) or cyclophosphamide (n=85). After a median follow-up of 31 months (IQR 19-42), median time to progression was significantly longer in the salvage ASCT than in the cyclophosphamide group (19 months [95% CI 16-25] vs 11 months [9-12]; hazard ratio 0·36 [95% CI 0·25-0·53]; p<0·0001). Frequently reported (in >10% of patients) grade 3-4 adverse events with PAD induction, salvage ASCT, and cyclophosphamide were: neutropenia (125 [43%] of 293 patients after PAD, and 63 [76%] of 83 patients in the salvage ASCT group vs 11 [13%] of 84 patients in the cyclophosphamide group), thrombocytopenia (150 [51%] after PAD, and 60 [72%] vs four [5%], respectively), and peripheral neuropathy (35 [12%] after PAD, and none vs none, respectively). INTERPRETATION: This study provides evidence for the improved efficacy of high-dose melphalan plus salvage ASCT when compared with cyclophosphamide in patients with relapsed multiple myeloma eligible for intensive therapy, which might help to guide clinical decisions regarding the management of such patients. FUNDING: Cancer Research UK.

Why do people seek reassurance and check repeatedly? An investigation of factors involved in compulsive behavior in OCD and depression.

Excessive reassurance-seeking (ERS) is a common problem among both obsessive-compulsive and depressed populations. However, the content and cognitive processes involved in ERS may differ in these populations according to the unique cognitive and behavioral characteristics demonstrated by each group. To assess factors involved in the onset, maintenance and termination of ERS and repeated checking, the current investigation employed a semi-structured interview with non-depressed obsessive-compulsive disorder (OCD) respondents (n=15), clinically depressed individuals without OCD (n=15), and healthy control participants (n=20). Results showed that whereas individuals with OCD reported seeking reassurance primarily about perceived general threats (e.g., fire, theft), the depressed group reported seeking reassurance primarily about perceived social threats (e.g., abandonment, loss of support). Clinical participants reported greater anxiety, sadness and perceived threat in association with ERS and repeated checking than healthy control participants. These findings are discussed in terms of cognitive-behavioral models of OCD and depression.

Determination of the fate and contribution of ex vivo expanded human bone marrow stem and progenitor cells for bone formation by 2.3ColGFP.

Bone marrow transplantation can provide an effective cell-based strategy to enhance bone repair. However, the fate of implanted cells and the extent of their contribution to bone osteoinduction remain uncertain. To define the fate of bone marrow-derived cells and their contribution in vivo, we used a bone-specific collagen I promoter (2.3Col) driving green fluorescent protein (GFP) (2.3ColGFP) within a lentiviral vector. Prior to in vivo cell fate determination, we verified a high efficiency of lentiviral transduction in human bone marrow stromal cells (hBMSCs), without altering the proliferation or differentiation potential of these cells. We showed that the 2.3ColGFP marker responded to endogenous transcriptional regulation signals. In a mouse ossicle model, we demonstrated that the 2.3ColGFP marker is able to specifically define human bone marrow-derived stem cells that enter the osteoblast lineage in vivo. In addition, cells labeled with 2.3ColGFP with the donor origin, directly make a major contribution to bone formation. Furthermore, we also demonstrated in a calvarial defect model that a mixture of human bone marrow-derived populations, have stronger bone regenerative potential than that of hBMSCs, and an optimal dose is required for bone regeneration by the mixed populations.

Anxiety-control strategies: is there room for neutralization in successful exposure treatment?

Cognitive-behavioral theory suggests that anxiety-control strategies such as neutralization, distraction and various forms of safety behavior have the potential to diminish the effectiveness of and/or interfere with exposure treatment. Yet, it is common practice when treating individuals with anxiety disorders to employ various anxiety-control strategies as a means of assisting clients/patients with difficult exposure situations. Questions surrounding the issue of which anxiety-control strategies help vs. hinder exposure-based treatments (and under which circumstances) have been a topic of much investigation and continue to be a focus of theoretical debate. The present article reviews several key studies which collectively shed some light on this debate. The evidence suggests that clients' anxiety-control strategies may be less likely to become counter-productive when: (i) they promote increases in self-efficacy, (ii) they do not demand excessive attentional resources, (iii) they enable greater approach behavior and integration of corrective information (via 'disconfirmatory experiences'), and (iv) they do not promote misattributions of safety. Theoretical and clinical implications of these findings are discussed, and future directions for research in this area are suggested.

Psychometric properties of the French and English versions of the Vancouver Obsessional-Compulsive Inventory and the Symmetry Ordering and Arranging Questionnaire.

The Vancouver Obsessional-Compulsive Inventory (VOCI) and the Symmetry Ordering and Arranging Questionnaire (SOAQ) are self-report measures that assess a wide variety of symptoms and features of obsessive-compulsive disorder (OCD) including checking, contamination, obsessions, hoarding, "just right", indecisiveness, and symmetry, ordering and arranging obsessions and compulsions. The original English versions of the VOCI and SOAQ have been shown to demonstrate excellent psychometric properties. The present study examined the reliability and validity of French translations of these measures in a non-clinical sample, and also involved the collection of supplementary psychometric information about the English versions of the scales from a new sample. Volunteer undergraduate students completed questionnaire packages including the VOCI and SOAQ, as well as measures of obsessive-compulsive, phobic and depressive symptomatology in their native language of either French or English. Results indicate that the French versions of the VOCI and SOAQ demonstrate similar and excellent psychometric properties to the English versions and that these measures are highly valid and reliable assessment tools for use in clinical and research applications in both languages.