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Momelotinib; Myelofibrosis; Patient-reported outcomes Momelotinib; Mielofibrosi; Resultats informats pel pacient Momelotinib; Mielofibrosis; Resultados informados por el paciente Background Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy. Methods Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to complement the interpretation of the landmark symptom results in the completed phase III SIMPLIFY studies of momelotinib in MF. MMRM compared mean change in TSS from baseline with Week 24 using data from all patient visits. Generalized estimating equations were used to estimate item-level odds ratios using multiple predictive imputations for missing data. Results Momelotinib and ruxolitinib groups reported similar overall symptom improvements, with a TSS difference of

Vertical transmission of Renibacterium salmoninarum has been well-documented in anadromous salmonids but not in hatchery-reared inland trout. We assessed whether the bacterium is vertically transmitted in cutthroat trout (Oncorhynchus clarkii) from a Colorado, USA hatchery, and assessed the rate of transmission from male and female brood fish. Adult brood fish were killed, tested for R. salmoninarum in kidney, liver, spleen, ovarian fluid, blood and mucus samples, then stripped of gametes to create 32 families with four infection treatments (MNFN, MNFP, MPFN, MPFP; M: male, F: female, P: positive, N: negative). Progeny from each treatment was sampled at 6 and 12 months to test for the presence of R. salmoninarum with an enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Our study indicated that vertical transmission was high and occurred among 60% of families across all infection treatments. However, the average proportion of infected progeny from individual families was low, ranging from 1% (MNFP, MPFN and MPFP treatments) up to 21% (MPFP treatment). Hatcheries rearing inland salmonids would be well suited to limit vertical transmission through practices such as lethal culling because any amount of transmission can perpetuate the infection throughout fish on a hatchery.

This review aims to provide an expert consensus statement to address the role of gene-panel testing in the diagnosis, prognosis and management of adult myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes (MDS/MPN) in Australia. This consensus statement was developed by an expert group, actively involved in gene panel testing in the area of MDS/MPN in Australia. This work was led by the chairs of the MDS (A/Prof A. Enjeti) and MPN (A/Prof D. Ross) working parties of the Australasian Leukaemia and Lymphoma Group (ALLG). The authors were selected after an expression of interest process on the basis of active laboratory involvement in gene panel testing, a specific demonstrated interest in MDS/MPN and/or publication record in this field. The authors were then allocated sections for literature review to identify the specific genes of interest for each MDS/MPN entity. At least two authors reviewed each section and an overarching diagnostic algorithm was developed by a consensus amongst all authors.

BACKGROUND: Janus kinase (JAK) inhibitors approved for myelofibrosis provide spleen and symptom improvements but do not meaningfully improve anaemia. Momelotinib, a first-in-class inhibitor of activin A receptor type 1 as well as JAK1 and JAK2, has shown symptom, spleen, and anaemia benefits in myelofibrosis. We aimed to confirm the differentiated clinical benefits of momelotinib versus the active comparator danazol in JAK-inhibitor-exposed, symptomatic patients with anaemia and intermediate-risk or high-risk myelofibrosis.METHODS: MOMENTUM is an international, double-blind, randomised, controlled, phase 3 study that enrolled patients at 107 sites across 21 countries worldwide. Eligible patients were 18 years or older with a confirmed diagnosis of primary myelofibrosis or post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis. Patients were randomly assigned (2:1) to receive momelotinib (200 mg orally once per day) plus danazol placebo (ie, the momelotinib group) or danazol (300 mg orally twice per day) plus momelotinib placebo (ie, the danazol group), stratified by total symptom score (TSS; FINDINGS: 195 patients were randomly assigned to either the momelotinib group (130 [67%]) or danazol group (65 [33%]) and received study treatment in the 24-week randomised treatment period between April 24, 2020, and Dec 3, 2021. A significantly greater proportion of patients in the momelotinib group reported a 50% or more reduction in TSS than in the danazol group (32 [25%] of 130 vs six [9%] of 65; proportion difference 16% [95% CI 6-26], p=0·0095). The most frequent grade 3 or higher treatment-emergent adverse events with momelotinib and danazol were haematological abnormalities by laboratory values: anaemia (79 [61%] of 130 vs 49 [75%] of 65) and thrombocytopenia (36 [28%] vs 17 [26%]). The most frequent non-haematological grade 3 or higher treatment-emergent adverse events with momelotinib and danazol were acute kidney injury (four [3%] of 130 vs six [9%] of 65) and pneumonia (three [2%] vs six [9%]).INTERPRETATION: Treatment with momelotinib, compared with danazol, resulted in clinically significant improvements in myelofibrosis-associated symptoms, anaemia measures, and spleen response, with favourable safety. These findings support the future use of momelotinib as an effective treatment in patients with myelofibrosis, especially in those with anaemia.FUNDING: Sierra Oncology.

A meeting of veterinary school faculty and partners, many associated with shelter medicine, and/or community medicine programming, was convened at the 2019 Shelter Medicine Veterinary Educators Conference in Pullman, WA to discuss challenges with shelter medicine program sustainability and defining the future. The discussion was facilitated by an outside consultant and is summarized in this manuscript. The goal of the meeting was to identify challenges and issues concerning the needs and goals for shelter medicine curricula to have long-term success in academic training. Four themes were identified in the transcripts including external pressure from leadership and other stakeholders, funder expectations, time horizons, and perceptions of shelters and shelter veterinarians. Addressing these challenges will be critical to ensuring stability in academic training in shelter medicine, a critical tool for both learning outcomes for general graduates and specific for veterinarians pursuing shelter medicine as a career.

LNK is a member of the SH2B family of adaptor proteins and is a non-redundant regulator of cytokine signalling. Cytokines are secreted intercellular messengers that bind to specific receptors on the surface of target cells to activate the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signalling pathway. Activation of the JAK-STAT pathway leads to proliferative and often inflammatory effects, and so the amplitude and duration of signalling are tightly controlled. LNK binds phosphotyrosine residues to signalling proteins downstream of cytokines and constrains JAK-STAT signalling. Mutations in LNK have been identified in a range of haematological and inflammatory diseases due to increased signalling following the loss of LNK function. Here, we review the regulation of JAK-STAT signalling via the adaptor protein LNK and discuss the role of LNK in haematological diseases.

This paper seeks to explore the PSPP decision of the German Constitutional Court and its effect on the monetary policy decisions taken by central banks. It begins by exploring the decision and its effect in Germany, together with its wider implications for the European Monetary Union before moving onto consider the standard of review that should be applied by the Courts when they are required to review central banks actions. Conclusions are reached to show that any standard of review should be limited because of the unique economic and political circumstances in which central bank decision making takes place. Keywords: Central Banking; Judicial Review; Proportionality; European Law; European Monetary Union.

While prevailing marketing practice is to encourage ever-stronger relationships between consumers and brands, such relationships are rare, and many consumers are relationship-averse or content with the status quo. The authors examine how marketers can more effectively manage existing brand relationships by focusing on the psychological distance between consumers and brands in order to match close (distant) brands with concrete (abstract) language in marketing communications. Through such matching, marketers can create a beneficial mindset-congruency effect leading to more favorable evaluations and behavior, even for brands that are relatively distant to consumers. Study 1 demonstrates the basic mindset-congruency effect, and Study 2 shows that it is capable of affecting donation behaviors. Study 3 documents two brand-level factors (search vs. experience goods, brand stereotypes) that moderate this effect in managerially relevant ways. Study 4 shows that activation of the mindset-congruency effect influences consumers to spend more and that these behaviors are moderated by consumer category involvement. The authors conclude with marketing and theoretical implications.

A particular point in time can be framed as either the start or end of a given time period. However, limited research is available on how such temporal landmarks influence consumers' judgments. This research addresses this issue by investigating how start vs. end temporal landmarks influence consumers' attentional focus and subsequent judgments. Six studies demonstrate that framing a temporal landmark as the start of a time period shifts visual attention to the left, while framing a temporal landmark as the end of a time period shifts visual attention to the right. By changing attentional focus within the visual-spatial environment, a temporal-spatial congruity between a temporal landmark (start vs. end) and the location of a target object (left vs. right) increases people's preference for that target object. Overall, these findings provide valuable implications for marketing theory and practice.

In this research, we identify health-based weight stereotypes in advertising and demonstrate that they can perpetuate unhealthy outcomes within overweight populations. We show that advertisements f...

Although the use of crowdsourced online panels for behavioral data collection is commonplace in media and advertising research, only recently have software advancements made it possible for researc...

Despite the scientific consensus concerning the current causes and future effects of anthropogenic global warming, there has been little to no improvement in public opinion, attitudes, or behavior related to its mitigation. This article examines how different information conveyance strategies affect belief in global warming. Three experiments reveal that a fundamental understanding of the underlying mechanism of global warming—the greenhouse gas effect—is integral to belief in the existence of global warming. Specifically, the current research demonstrates that persuasive messaging incorporating an explanation of the mechanism (versus consequences) underlying global warming leads to belief change (study 1); that this effect is moderated by political orientation, such that the effect of mechanism-understanding on global warming belief is greater for conservatives (study 1, 2, and 3); that understanding of the mechanism underlying global warming affects willingness to engage in sustainable activities and buying socially conscious products (study 2); and that the effect persists over time and can influence actual donation behavior (study 3). Social, public policy, and marketing implications for this strategy are discussed.

MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, was evaluated (vs DAN) in a pivotal phase 3 study of MF patients previously treated with a JAK inhibitor (JAKi). This subgroup analysis evaluated MOMENTUM patients with baseline platelet counts ≤150 × 10Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; total symptom score (TSS) ≥10; hemoglobin10 g/dL; prior JAKi ≥90 days, or ≥28 days if RBC transfusions ≥4 units in 8 weeks or Grade 3/4 thrombocytopenia, anemia, or hematoma; palpable spleen ≥5 cm; platelets ≥25 × 10TSS response (≥50% reduction from baseline) rate at week 24. Secondary endpoints at week 24: transfusion independence (TI) rate, splenic response rate (SRR; ≥25% volume reduction from baseline), TSS change from baseline, SRR (≥35% reduction), and rate of zero transfusions since baseline.Mean baseline TSS: 29 MMB, 26 DAN, hemoglobin: 8.1 MMB, 7.8 DAN g/dL, and platelets: 74 × 10In symptomatic, anemic, and thrombocytopenic MF patients, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need in thrombocytopenic MF patients. NCT04173494.

Contribution analysis (CA) is being increasingly favoured as a policy evaluation tool. This includes application to evaluate alcohol and drug policies. This paper reflects on one such example and begins by providing a brief overview of CA as an evaluative research method. It then describes the way in which CA was applied to evaluate alcohol and drug policy in Wales, one of the constituent countries of the UK. This paper reports on two issues. First, how the theory of CA was translated into practice. Second, the key learning points for us as evaluators that arose out of the utilisation of this method. The article highlights that our use of CA enabled a rich exploration of programmes within their contextual setting, and had a range of limitations and considerable challenges associated with identifying and explaining causalities. Within these methodological discussions, we also illustrate how the policy was more successful in elements closer to its nomenclature framing; i.e. harm reduction, than it was to other incorporated aims. The analysis presented in this paper will be useful across a range of jurisdictions where the need to evaluate drug and alcohol policy and practice initiatives may arise.

Marketers seeking to understand diverse customers risk using stereotypes. That market forces will deal with the problem of stereotyping may be an overly strong assumption and so we ask: (1) How might OGHB impact a marketing decision? And (2) are the effects of this likely to persist in markets, i.e., does it matter? Our research combines the psychology of prejudice with game theory to model competitive market outcomes. We model marketers relying on stereotypes—technically experiencing out-group homogeneity bias (OGHB); the tendency to perceive out-groups as less varied simply because we are unable to identify with them. Our core finding is that in competitive market entry OGHB can have negative consequences for the competitor of those experiencing the bias. This comes from a reduction in the value of the market, rather than any gains made by those employing stereotypes. Bias resembles a negative externality and non-market efforts to reduce stereotyping may be in the interests of not just consumers but also the competitors of those using stereotypes.

7015 Background: Ruxolitinib (RUX), a Janus kinase (JAK) 1/2 inhibitor, is the current standard of care for patients (pts) with myelofibrosis (MF) that improves splenomegaly and disease symptoms with limited impact on disease biology. Many pts lose response over time, highlighting an unmet need for novel therapies. Navitoclax (NAV) is an oral, small-molecule inhibitor of BCL-XL and BCL-2 that has a synergistic effect when used in combination with JAK inhibitors to enhance apoptosis. This ongoing, open-label, multicenter, phase 2 trial (NCT03222609) is evaluating the efficacy and safety of NAV with/without RUX in pts with MF. Here, we report results from JAK inhibitor-naïve pts treated with NAV+RUX. Methods: Enrolled pts had primary or secondary MF with splenomegaly (DIPSS ≥INT-1) and did not receive prior JAK-2 therapy or bromodomain and extraterminal motif (BET) inhibitors. Pts initiated NAV at 100 mg QD or 200 mg QD if baseline (BL) platelet count was ≤150 × 109/L or >150 × 109/L, respectively. RUX was given BID with starting dose based on BL platelet count per local label. The primary endpoint was spleen volume reduction of ≥35% (SVR35) from BL at wk 24. Key secondary endpoints were ≥50% reduction in total symptom score (TSS50), bone marrow (BM) fibrosis reduction, and anemia response. Adverse events (AEs) were monitored throughout the study. Results: As of Oct 04, 2021, 32 pts received NAV+RUX. Median duration of f/u was 6.1 (range, 1.9 ─ 18.6) mos. 28 (88%) pts received NAV 200 mg and 4 (13%) received 100 mg OD. Median age was 69 (44 ─ 83) yrs, and median spleen volume was 1889.08 cm3 (645.6 ─ 7339.6). Median NAV and RUX exposures were 24.1 (5.1 ─ 80.9) and 20.1 (0.1 ─ 80.1) wks, respectively. 31 (97%) pts reported ≥1 AE (Grade ≥3 AEs, 25 [78%]; serious AEs, 6 [19%]). Most common Grade ≥3 AEs were anemia (34%), thrombocytopenia (31%), and neutropenia (19%). 3 (9%) and 2 (6%) pts reported an AE leading to NAV and RUX discontinuation, respectively, and 2 (6%; 1 PD, 1 cardiac disorder unrelated to NAV) AEs led to death ≤30 days after last NAV dose. SVR35 was achieved by 52% of evaluable pts at wk 24 (SVR35 in INT-2, 50%; HR, 33%) and by 76% at any time on treatment (Table). Median time to first SVR35 was 12.1 (11 ─ 47) wks. Conclusions: The combination of NAV+RUX was well tolerated and demonstrated early and robust reductions in spleen volume, anemia, and BM fibrosis in pts without prior JAK-2 inhibitor exposure. SVR35, TSS50, and BM fibrosis improved over time. Clinical trial information: NCT03222609. [Table: see text]

7061 Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on MF symptoms, RBC transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials, including in MF patients (pts) with thrombocytopenia. MOMENTUM is a pivotal phase 3 study of symptomatic and anemic MF pts previously treated with a JAK inhibitor (JAKi) testing MMB vs DAN. This analysis evaluated MOMENTUM pts with baseline (BL) platelet counts (PLT) ≤150 x 109/L. Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; Hgb 9/L. JAKi taper and washout was ≥21 days. Randomization: 2:1 to MMB 200 mg QD plus DAN placebo or DAN 600 mg QD plus MMB placebo for 24 wks. Primary endpoint: TSS response (≥50% reduction from BL) rate at wk 24. Key secondary endpoints, assessed sequentially at wk 24: RBC transfusion independence (TI) rate, splenic response rate (SRR; ≥25% reduction in volume from BL), change from BL in TSS, SRR (≥35% reduction from BL) and rate of zero transfusions since BL. Results: 60 (74%) of 81 MMB pts and 25 (58%) of 43 DAN pts with BL PLT ≤150 x 109/L completed the 24-week randomized treatment (RT) phase. Median BL TSS were 29 (MMB) and 24 (DAN), Hgb were 7.9 (MMB) and 8.0 (DAN) g/dL, and PLT were 67 x 109/L (MMB) and 64 x 109/L (DAN). Prior JAKi was ruxolitinib in 124 pts (100%) and fedratinib in 6 pts (5%). Efficacy results are in Table. These results are consistent with the overall ITT analysis set (N=195). Most common Gr ≥3 TEAEs in the RT phase were thrombocytopenia (MMB, 31%; DAN, 16%) and anemia (MMB, 7%; DAN, 14%); Gr ≥3 bleeding events occurred in 9% of MMB and 5% of DAN pts. TEAEs led to study drug discontinuation in 15% of MMB and 19% of DAN pts in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN [HR (95% CI)=0.490 (0.195, 1.235)]. Additional analyses of pts with BL PLT 9/L (N=100) and BL PLT 9/L (N=31) show similar treatment effects of MMB vs DAN. Conclusions: In thrombocytopenic MF pts who were symptomatic and anemic, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses and showed comparable safety and favorable survival. MMB may address a critical unmet need in thrombocytopenic MF pts. Clinical trial information: NCT04173494. [Table: see text]

7002 Background: MMB, an oral JAK1/2 and ACVR1/ALK2 inhibitor, showed clinical activity on MF symptoms, RBC transfusion requirements (anemia), and spleen volume in the SIMPLIFY trials. This pivotal phase 3 study of MF patients (pts) previously treated with a JAK inhibitor (JAKi) tested MMB vs DAN on key symptom, anemia, and spleen volume endpoints at 24 weeks (wks). Methods: Eligibility: Primary or post-ET/PV MF; DIPSS high risk, Int-2, or Int-1; MF Symptom Assessment Form Total Symptom Score (MFSAF TSS) ≥10; Hgb 9/L. BL TI was 13% (MMB) and 15% (DAN). Prior JAKi was ruxolitinib in 195 pts (100%) and fedratinib in 9 pts (5%). All primary and key secondary endpoints were met (Table). Most common Gr ≥3 TEAEs in the RT phase of the study were thrombocytopenia (MMB, 22%; DAN, 12%) and anemia (MMB, 8%; DAN, 11%). Gr ≥3 infections occurred in 15% of MMB and 17% of DAN pts. Peripheral neuropathy occurred in 5 (4%) of MMB (all Gr ≤2) and 1 (2%) of DAN (Gr ≤2) pts in the RT phase, and none discontinued study drug. Overall, TEAEs led to study drug discontinuation in 18% of MMB and 23% of DAN pts in RT phase. A trend toward improved OS up to wk 24 was seen with MMB vs DAN (HR=0.506, p=0.0719). Conclusions: In symptomatic and anemic MF pts, MMB was superior to DAN for symptom responses, transfusion requirements, and spleen responses with comparable safety and favorable survival. MMB may address a critical unmet need, particularly in MF pts with anemia. Clinical trial information: NCT04173494. [Table: see text]

Objective Sleep disturbance in hospital is common. This pilot randomized controlled trial assessed a sleep clinical pathway compared with standard care in improving sleep quality, engagement in therapy and length of stay in musculoskeletal inpatient rehabilitation. Methods Participants (n = 51) were randomized to standard care (“control”, n =29) or sleep clinical pathway (“intervention”, n = 22). Outcome measures included: Pittsburgh Sleep Quality Index (PSQI), Hopkins Rehabilitation Engagement Rating Scale (HRERS), Fatigue Severity Scale (FSS), Patient Satisfaction with Sleep Scale, and actigraphy. Assessment time-points were at admission and before discharge from rehabilitation. Results No significant differences were found between groups for any outcome measure. As a cohort (n = 51), there were significant improvements from admission to discharge in sleep quality (PSQI (−2.31; 95% confidence interval (95% CI) −3.33 to −1.30; p

PurposeThe purpose of this paper is to explore a range of key deliberations with regards to adopting participatory action research (PAR) and privileged access interviewer (PAI) approaches and methodologies within research on substance use.Design/methodology/approachThis paper is a reflective piece; it adopts a mixture of applied practice and theory considerations. These conceptualisations capture what are still relatively early understandings and uses of such methodologies, acquired across several decades of research and service provision experiences. The paper is structured around some of the sequences of the research process and as such provides a broad framework for such approaches.FindingsPAR and PAI approaches utilise several key theoretical considerations. There are many critical issues associated with adopting these approaches, including those of ethics, funding, involvement, language, resources and support. Three key principle reasons (moral, political and research based) help explain why the authors should see more adoption of such approaches in substance use-related research.Research limitations/implicationsThis paper represents authors’ views which are by their nature very subjective.Practical implicationsImplementation of the key considerations highlighted within this paper can lead to an active adoption of PAR and PAI methodologies within alcohol and drug research. Increasing the use of such methodologies will allow commissioners, researchers and service providers to develop a more nuanced understanding of the experiences of and responses to alcohol and drug use.Originality/valueThis paper captures critical conversations at a time of increased calls for service user involvement across all aspects of alcohol and other drug provision, including evaluation and research

This research suggests that experiencing action regret induces a change in psychological and physical warmth, motivating individuals to ameliorate that change via interaction with objects that are perceived to be physically or psychologically opposite in temperature. Experiment 1 revealed individuals experiencing action regret felt more self-conscious emotions, and subsequently preferred cold (versus hot) drinks. Experiment 2 replicated this effect and ruled out arousal as a possible alternative explanation. Experiment 3 furthered this link by demonstrating that those feeling more self-conscious emotions felt warmer and subsequently preferred cold (versus hot) drinks. Finally, experiment 4 found that advertisements manipulated for temperature (e.g., cold climate) mitigated the psychological effects of action regret. We interpret the results of these four studies within the emerging field of embodied cognition, which argues that our understanding of emotional concepts is grounded in, and can be influenced by, physical experiences.

The use of ethnic imagery in visual identities of brands, such as those used by professional sports franchises, has long been a contentious issue in American society. This research investigates the oft-voiced argument that ethnic brand imagery perpetuates negative stereotypes (a claim that has been subject to very little empirical scrutiny) and identifies conditions under which encountering such brand imagery strengthens both positive and negative implicit stereotypes. Within the context of American Indian brand imagery, two laboratory experiments (Studies 1 and 2) and a quasi-experimental field study (Study 3) revealed that the effects of ethnic brand imagery on stereotypes depend on the viewer's political identity. Exposure to ethnic brand imagery strengthened implicit stereotypes only among more liberal individuals, consistent with the idea that liberals tend to hold more malleable views. These findings demonstrate measurable negative effects of ethnic brand imagery on implicit stereotypes and support the view that the use of such imagery can carry detrimental societal consequences.

Taking advantage of additive manufacturing and 3D printing, we have designed a 3D printed insole with embedded plantar pressure sensor arrays. 3D printing allowed us to uniquely design a multitude of sensors. With the use of extrusion-based 3D printers, we produced a model that printed both the resistive circuits and a complete insole simultaneously. These distinctive technologies have given us the capability to capture valuable pressure data from the insole of the foot. Analog signals sent from the pressure sensor arrays are received and processed through an attached multiplexer designed specifically for this application. The signal is then digitized and transmitted over the SPI to a microcontroller via Bluetooth Low Energy, to an android device to allow the user to easily record and interpret the pressure data in real-time. The android device houses a pressure mapping view to show the gradient of force throughout the insole.

Acute myeloid leukaemia (AML) is characterized by the accumulation of transformed immature myeloid blasts. While most AML patients treated with standard therapy have poor outcomes, in the APL disease subtype retinoic acid induces leukaemia maturation and can be curative in combination with arsenic trioxide. Recently approved mutant IDH1/2 inhibitors also induce AML maturation, renewing interest in AML differentiation therapy. To examine differentiation therapy dynamics in vivo we have generated a novel mouse AML model driven by reversible RNAi-mediated knockdown of the myeloid transcription factor PU.1. Restoration of endogenous PU.1 in established AML in vivo triggers synchronous differentiation of leukemic blasts and disease clearance. However, despite near-complete remission, mice reproducibly relapse with immature AML. Notably, in vivo time course studies reveal that one week after PU.1 restoration leukemic blasts differentiate into two mature myeloid lineages with distinct immunophenotype and morphology. AML-derived SSClowLy6G+ cells resembling neutrophils initially predominate but are rapidly eradicated in vivo. In contrast, high resolution flow and imaging indicates that mature AML-derived SSChighF4/80+SigF+ eosinophil-like cells persist at low numbers in specific organs during disease remission and appear to seed relapse. In mice transplanted with AML blasts lacking the essential eosinophil lineage transcription factor GATA1, in vivo PU.1 restoration triggers neutrophil but not eosinophil lineage differentiation and thereby eliminates residual disease. These results demonstrate that AML differentiation therapy can produce long-lived sublineages of mature AML-derived cells from which relapse can originate. Understanding the multilineage potential of AML blasts in individual patients may inform new strategies to improve differentiation therapy outcomes.

Extant embodied cognition research suggests that individuals can reduce a perceived lack of interpersonal warmth by substituting physical warmth, and vice versa. We suggest that this behavior is self-regulatory in nature and that this self-regulation can be accomplished via consumptive behavior. Experiment 1 found that consumers perceived ambient temperature to be significantly lower when eating alone compared to eating with a partner. Experiment 2 found that consuming a cool (vs. warm) drink led individuals to generate more socially-oriented attributes for a hypothetical product. Experiment 3 found that physically cooler individuals desired a social consumption setting, whereas physically warmer individuals desired a lone consumption setting. We interpret these results within the context of self-regulation, such that perceived physical temperature deviations from a steady state unconsciously motivate the individual to find bodily balance in order to alleviate that deviation.

Following the tenets of the selective accessibility model of assimilation and contrast, three studies observed implicit consumer self-concept assimilation (contrast) to age-based imagery when the discrepancy between the self-concept and advertisement imagery was moderate (extreme). However, these responses were not fully automatic as only consumers who processed user imagery reflectively demonstrated increased accessibility of similarity/dissimilarity information. Impulsive processing of the user imagery instead increased the accessibility of consumer's pre-existing dominant self-age association. A final experiment revealed that these changes in the active-self mediated response to subsequently advertised products. Taken together, these results support a two-systems model of cognition and suggest that assimilation/contrast responses to advertising and subsequent behavior are influenced by the consumer's processing strategy.

The current research draws from ambivalent sexism theory to examine potential gender differences in the quantity and quality of developmental work experiences. In a sample of managers in the energy industry, men and women reported participating in a similar number of developmental experiences (with comparable levels of support), but men rated these experiences as more challenging and received more negative feedback than did women. Similarly, a sample of female managers in the health care industry reported comparable amounts, but less challenging types, of developmental experiences than their male counterparts'. The results of three complementary experiments suggest that benevolent sexism is negatively related to men's assignment of challenging experiences to female targets but that men and women were equally likely to express interest in challenging experiences. Taken together, these results suggest that stereotype-based beliefs that women should be protected may limit women's exposure to challenging assignments, which in turn may partially explain the underrepresentation of women at the highest levels of organizations. © The Author(s) 2012.

Some undergraduate programmes require evidence of baseline numeracy skills as a condition of entry. With a widened entry gate into higher education and a recognised ‘mathematics problem’ in society, students wishing to enrol onto degree programmes that require evidence of numeracy often find it difficult to provide such evidence. Numeracy skills of pre‐registration nursing students are an issue of particular concern. Some undergraduate nursing programmes require prospective students who are applying for places to undertake a numeracy entrance test as part of the selection process. Evidence from numeracy selection tests conducted at one university indicated that many applicants struggled to demonstrate competence in basic numerical concepts. On the basis of this evidence, the School of Nursing at Kingston University/St George’s University of London (KU/SGUL), in partnership with Merton College of Further Education, designed and delivered an innovative pre‐entrance test numeracy development programme for pr...

Researchers are focusing on developing implicit measures of personality to address concerns related to the faking of self-report measures. The present study examined the validity and fakeability of Implicit Association Test (IAT) measures of personality self-concept in a repeated-measures design (N = 33). People’s predictions about how they represented themselves on the measures were also assessed. Results indicated that participants were able fake self-report measures when instructed to do so and that they could accurately predict how they represented themselves on these measures. Participants were also able to fake an IAT measure of Extraversion, but were unable to fake an IAT measure of Conscientiousness or predict how they represented themselves on either IAT measure.