Stefania Paolini

Effects of Direct and Indirect Cross-Group Friendships on Judgments of Catholics and Protestants in Northern Ireland: The Mediating Role of an Anxiety-Reduction Mechanism

Recent evidence suggests that both direct and indirect friendship with outgroup members (knowledge of ingroup members’ friendship with outgroup members) can reduce prejudice toward the outgroup. Two surveys of cross-community relationships in Northern Ireland, using a student sample (N = 341) and a representative sample of the general population (N = 735), tested whether (a) direct and indirect friendships had generalized effects on both prejudice and perceived outgroup variability and (b) reduced anxiety about future encounters with outgroup members mediated such relationships. Structural equation modeling confirmed that, in both samples, direct and indirect cross-group friendships between Catholics and Protestants were associated with reduced prejudice toward the religious outgroup and increased perceived outgroup variability, via an anxiety-reduction mechanism. It is argued that emerging generalization hypotheses help to integrate both cognition and affect and interpersonal and intergroup approaches to contact.

Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients

Thirteen patients with acute myeloid leukemia, 5 with active disease, 2 in molecular relapse, and 6 in morphologic complete remission (CR; median age, 62 years; range, 53-73 years) received highly purified CD56(+)CD3(-) natural killer (NK) cells from haploidentical killer immunoglobulin-like receptor-ligand mismatched donors after fludarabine/cyclophosphamide immunosuppressive chemotherapy, followed by IL-2. The median number of infused NK cells was 2.74 × 10(6)/Kg. T cells were < 10(5)/Kg. No NK cell-related toxicity, including GVHD, was observed. One of the 5 patients with active disease achieved transient CR, whereas 4 of 5 patients had no clinical benefit. Both patients in molecular relapse achieved CR that lasted for 9 and 4 months, respectively. Three of 6 patients in CR are disease free after 34, 32, and 18 months. After infusion, donor NK cells were found in the peripheral blood of all evaluable patients (peak value on day 10). They were also detected in BM in some cases. Donor-versus-recipient alloreactive NK cells were shown in vivo by the detection of donor-derived NK clones that killed recipients targets. Adoptively transferred NK cells were alloreactive against recipients cells, including leukemia. In conclusion, infusion of purified NK cells is feasible in elderly patients with high-risk acute myeloid leukemia. This trial was registered at www.clinicaltrial.gov as NCT00799799.

Identification and molecular characterization of recurrent genomic deletions on 7p12 in the IKZF1 gene in a large cohort of BCR-ABL1-positive acute lymphoblastic leukemia patients: on behalf of Gruppo Italiano Malattie Ematologiche dell'Adulto Acute Leukemia Working Party (GIMEMA AL WP)

The BCR-ABL1 fusion gene defines the subgroup of acute lymphoblastic leukemia (ALL) with the worst clinical prognosis. To identify oncogenic lesions that combine with BCR-ABL1 to cause ALL, we used Affymetrix Genome-Wide Human SNP arrays (250K NspI and SNP 6.0), fluorescence in situ hybridization, and genomic polymerase chain reaction to study 106 cases of adult BCR-ABL1-positive ALL. The most frequent somatic copy number alteration was a focal deletion on 7p12 of IKZF1, which encodes the transcription factor Ikaros and was identified in 80 (75%) of 106 patients. Different patterns of deletions occurred, but the most frequent were those characterized by a loss of exons 4 through 7 (Delta4-7) and by removal of exons 2 through 7 (Delta2-7). A variable number of nucleotides (patient specific) were inserted at the conjunction and maintained with fidelity at the time of relapse. The extent of the Delta4-7 deletion correlated with the expression of a dominant-negative isoform with cytoplasmic localization and oncogenic activity, whereas the Delta2-7 deletion resulted in a transcript lacking the translation start site. The IKZF1 deletion also was identified in the progression of chronic myeloid leukemia to lymphoid blast crisis (66%) but never in myeloid blast crisis or chronic-phase chronic myeloid leukemia or in patients with acute myeloid leukemia. Known DNA sequences and structural features were mapped along the breakpoint cluster regions, including heptamer recombination signal sequences recognized by RAG enzymes during V(D)J recombination, suggesting that IKZF1 deletions could arise from aberrant RAG-mediated recombination.

The Contact Caveat : Negative Contact Predicts Increased Prejudice More Than Positive Contact Predicts Reduced Prejudice

Contact researchers have largely overlooked the potential for negative intergroup contact to increase prejudice. In Study 1, we tested the interaction between contact quantity and valence on prejudice toward Black Australians (n = 1,476), Muslim Australians (n = 173), and asylum seekers (n = 293). In all cases, the association between contact quantity and prejudice was moderated by its valence, with negative contact emerging as a stronger and more consistent predictor than positive contact. In Study 2, White Americans (n = 441) indicated how much positive and negative contact they had with Black Americans on separate measures. Although both quantity of positive and negative contact predicted racism and avoidance, negative contact was the stronger predictor. Furthermore, negative (but not positive) contact independently predicted suspicion about Barack Obama’s birthplace. These results extend the contact hypothesis by issuing an important caveat: Negative contact may be more strongly associated with increased racism and discrimination than positive contact is with its reduction.

Grandparent-Grandchild Contact and Attitudes Toward Older Adults: Moderator and Mediator Effects

Two studies tested the intergroup contact hypothesis in the context of the grandparent-grandchild relationship. The hypothesis suggests that contact with an out-group member has more influence on attitudes toward the out-group when group memberships are salient. In Study 1, the predicted link was found but only for grandparents with whom the grandchild had more frequent contact. The second study examined only the most frequent grandparent relationship and replicated the effect. This study also investigated the role of various mediators of the link between quality of contact and attitudes, as well as quality of contact and perceived out-group variability. Perspective taking, anxiety, and accommodation mediated the effects of contact on attitudes, whereas individuation and self-disclosure mediated the effects of contact on perceived out-group variability. Moderated mediational analysis indicated that the moderating effect of group salience occurs between quality of contact and the mediator, not between the mediator and attitudes.

Negative Intergroup Contact Makes Group Memberships Salient: Explaining Why Intergroup Conflict Endures

Drawing from the intergroup contact model and self-categorization theory, the authors advanced the novel hypothesis of a valence-salience effect, whereby negative contact causes higher category salience than positive contact. As predicted, in a laboratory experiment of interethnic contact, White Australians (N = 49) made more frequent and earlier reference to ethnicity when describing their ethnic contact partner if she had displayed negative (vs. positive, neutral) nonverbal behavior. In a two-wave experimental study of retrieved intergenerational contact, American young adults (N = 240) reported age to be more salient during negative (vs. positive) contact and negative contact predicted increased episodic and chronic category salience over time. Some evidence for the reverse salience-valence effect was also found. Because category salience facilitates contact generalization, these results suggest that intergroup contact is potentially biased toward worsening intergroup relations; further implications for theory and policy making are discussed.

The efficacy of imatinib mesylate in patients with FIP1L1-PDGFRα-positive hypereosinophilic syndrome. Results of a multicenter prospective study

Background and Objectives The hypereosinophilic syndrome (HES) may be associated with the fusion of the platelet derived growth factor receptor α (PDGFRα) gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated PDGFRα tyrosine kinase. These cases with FIP1L1-PDGFRα rearrangement have been reported to be very sensitive to the tyrosine kinase inhibitor imatinib mesylate. Design and Methods A prospective multicenter study of idiopathic or primary HES was established in 2001 (Study Protocol Registration no. NCT 0027 6929). One hundred and ninety-six patients were screened, of whom 72 where identified as having idiopathic or primary HES and 63 were treated with imatinib 100 to 400 mg daily. Results Twenty-seven male patients carried the FIP1L1-PDGFRα rearrangement. All 27 achieved a complete hematologic remission (CHR) and became negative for the fusion transcripts according to reverse transcriptase polymerase chain reaction (RT-PCR) analysis. With a median follow-up of 25 months (15–60 months) all 27 patients remain in CHR and RT-PCR negative, and continue treatment at a dose of 100 to 400 mg daily. In three patients imatinib treatment was discontinued for few months, the fusion transcript became rapidly detectable, and then again undetectable upon treatment reassumption. Thirty-six patients did not carry the rearrangement; of these, five (14%) achieved a CHR, which was lost in all cases after 1 to 15 months. Interpretation and Conclusions All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFRα rearrangement. For all patients with this rearrangement, chronic imatinib treatment at doses as low as 100 mg daily ensures complete and durable responses.

European development of clofarabine as treatment for older patients with acute myeloid leukemia considered unsuitable for intensive chemotherapy.

PURPOSE Treatment options for older patients with acute myeloid leukemia (AML) who are not considered suitable for intensive chemotherapy are limited. We assessed the second-generation purine nucleoside analog, clofarabine, in two similar phase II studies in this group of patients. PATIENTS AND METHODS Two consecutive studies, UWCM-001 and BIOV-121, recruited untreated older patients with AML to receive up to four or six 5-day courses of clofarabine. Patients in UWCM-001 were either older than 70 years or 60 to 69 years of age with poor performance status (WHO > 2) or with cardiac comorbidity. Patients in BIOV-121 were >or= 65 years of age and deemed unsuitable for intensive chemotherapy. RESULTS A total of 106 patients were treated in the two monotherapy studies. Median age was 71 years (range, 60 to 84 years), 30% had adverse-risk cytogenetics, and 36% had a WHO performance score >or= 2. Forty-eight percent had a complete response (32% complete remission, 16% complete remission with incomplete peripheral blood count recovery), and 18% died within 30 days. Interestingly, response and overall survival were not inferior in the adverse cytogenetic risk group. The safety profile of clofarabine in these elderly patients with AML who were unsuitable for intensive chemotherapy was manageable and typical of a cytotoxic agent in patients with acute leukemia. Patients had similar prognostic characteristics to matched patients treated with low-dose cytarabine in the United Kingdom AML14 trial, but had significantly superior response and overall survival. CONCLUSION Clofarabine is active and generally well tolerated in this patient group. It is worthy of further evaluation in comparative trials and might be of particular use in patients with adverse cytogenetics.

Reducing prejudice via direct and extended cross-group friendship

One of the most exciting developments in intergroup contact theory is the idea that a certain type of contact, cross-group friendship, might be particularly effective at reducing prejudice. In this chapter we review research on two types of cross-group friendship. Direct cross-group friendship refers to friendships that develop between members of different groups. Extended cross-group friendship, on the other hand, refers to vicarious experience of cross-group friendship, the mere knowledge that other ingroup members have cross-group friends. We consider the relationship between both types of cross-group friendship and prejudice and the processes that mediate and moderate these relationships. The research highlights the respective strengths and weaknesses of direct and extended cross-group friendship and illustrates how they might be practically combined in efforts to improve intergroup relations.

Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors.

Dasatinib and nilotinib are tyrosine kinase inhibitors (TKIs) developed to overcome imatinib resistance in Philadelphia-positive leukemias. To assess how Bcr-Abl kinase domain mutation status evolves during sequential therapy with these TKIs and which mutations may further develop and impair their efficacy, we monitored the mutation status of 95 imatinib-resistant patients before and during treatment with dasatinib and/or nilotinib as second or third TKI. We found that 83% of cases of relapse after an initial response are associated with emergence of newly acquired mutations. However, the spectra of mutants conferring resistance to dasatinib or nilotinib are small and nonoverlapping, except for T315I. Patients already harboring mutations had higher likelihood of relapse associated with development of further mutations compared with patients who did not harbor mutations (23 of 51 vs 8 of 44, respectively, for patients who relapsed on second TKI; 13 of 20 vs 1 of 6, respectively, for patients who relapsed on third TKI).