Episodic Future Thinking In Mathematical Situations

Episodic future thinking is a process of mentally projecting one\u27s self into a future event, allowing the event to be experienced before it actually occurs (Atance & O\u27Neill, 2001). The current study explores the possibility that students engage in episodic future thinking while solving mathematical tasks. Participating students were given mathematical situations and verbalized thoughts that emerged as they planned resolutions to the situations. All participants exhibited episodic future thinking and we present a categorization of these thoughts. Given extant results on the positive influence episodic future thinking has on general problem-solving ability, we propose that a similar influence might exist on mathematical problem solving

Posttransplantation Maintenance Therapy and Optimal Frontline Therapy in Myeloma

One of the major efforts to improve the results of intensive therapy and autologous stem cell transplantation (ASCT) in multiple myeloma involves the integration of novel agents into the transplantation sequence. This can include their administration before, during, and after the transplantation procedure. Several phase 2 and 3 studies have evaluated the use of novel agents as part of induction therapy before transplantation to produce higher response rates and progression-free survival (PFS). Similarly, posttransplantation maintenance-or consolidation-with these agents consistently improves PFS. Survival benefits have been more difficult to demonstrate, although one trial using bortezomib before and after transplantation and a second using lenalidomide as maintenance have shown significantly longer survival times. This article reviews the different regimens used with ASCT, with an emphasis on randomized trials

Genomic Aberrations and Survival of Patients with Light-Chain-Only Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

The majority of patients with multiple myeloma (MM) have intact immunoglobulin, but in a subset of patients (∼15%), their tumors produce monoclonal light chains only (LCO). Although specific genomic aberrations have emerged as a major prognostic factor in MM, their incidence and prognostic impact on LCO myeloma patients are not clear. We therefore investigated a cohort of 86 LCO MM cases diagnosed and treated with autologous stem cell transplantation at our institution. Overall, genomic risk factors del(13q), del(17p), t(4;14), 1p loss, and 1q21 gain were detected by cytoplasmic fluorescence in situ hybridization (cIg-FISH) in 40.6%, 18.5%, 11.9%, 18.8%, and 25% of the cases, respectively. Patients with del(13q) and 1q gains had a significantly shorter overall survival (OS) (median 80.4 vs 56.2 months, P = .021; median 77.9 vs 26.9 months, P = .006, respectively) and shorter progression-free survival (PFS) (median 33.4 vs 15.8 months, P = .002; median 33.4 vs 19.1 months, P = .011, respectively) than those without the genetic abnormalities. In addition, 1p loss was significantly associated with shorter PFS (median 37.9 vs 18.2 months, P = .001). There was no significant difference in PFS or OS in patients with or without t(4;14) or del(17p). On multivariate analysis, del(13q) was an independent prognostic factor for PFS and OS

Relational processing demands and the role of spatial context in the construction of episodic simulations

Reports on differences between remembering the past and imagining the future have led to the hypothesis that constructing future events is a more cognitively demanding process. However, factors that influence these increased demands, such as whether the event has been previously constructed and the types of details comprising the event, have remained relatively unexplored. Across two experiments, we examined how these factors influence the process of constructing event representations by having participants repeatedly construct events and measuring how construction times and a range of phenomenological ratings changed across time points. In Experiment 1, we contrasted the construction of past and future events and found that, relative to past events, the constructive demands associated with future events are particularly heightened when these events are imagined for the first time. Across repeated simulations, future events became increasingly similar to past events in terms of construction times and incorporated detail. In Experiment 2, participants imagined future events involving two memory details (person, location) and then reimagined the event either (a) exactly the same, (b) with a different person, or (c) in a different location. We predicted that if generating spatial information is particularly important for event construction, a change in location will have the greatest impact on constructive demands. Results showed that spatial context contributed to these heightened constructive demands more so than person details, consistent with theories highlighting the central role of spatial processing in episodic simulation. We discuss the findings from both studies in the light of relational processing demands and consider implications for current theoretical frameworks

Interest in coloured objects and behavioural budgets of individual captive freshwater turtles

Recent studies showed that freshwater turtles display inter-individual differences in variousbehavioural traits, which may influence their health and welfare in captivity due to differences inresponse to husbandry and enrichment strategies and in ability to cope with the limitations of thecaptive environment. This study investigated a possible correlation between individual level ofescape behaviour under standard enrichment conditions and level of interest in coloured objects ina group of cooters Pseudemys sp. and sliders Trachemys scripta ssp. on display at a public aquarium.Interest in different colours, colour preference and individual differences in behavioural changes inthe presence of the new enrichment were also studied. Turtles categorised as ‘high’ and ‘moderateescape behaviour’ (17–34 of behavioural budget) showed more interest in coloured objects andtended to display less escape behaviour in their presence, while turtles categorised as ‘low escapebehaviour’ (<10 of behavioural budget) were less interested in coloured objects and tended todisplay more escape behaviour in their presence. Overall, there was more interest in yellow than inred, white or green objects, with more contacts with coloured objects before feeding and at the startof each observation period and a preference for yellow against red objects. The individual differencesin behavioural changes in the presence of the new enrichment suggested that more studies into colourpreference and response to novelty in turtles would be beneficial to ensure that no individuals areunduly stressed by new enrichments

Targeting CD47/TNFAIP8 by miR-155 overcomes drug resistance and inhibits tumor growth through induction of phagocytosis and apoptosis in multiple myeloma

The mechanisms of drug resistance in multiple myeloma are poorly understood. Here we show that CD47, an integrin-associated receptor, is significantly upregulated in drug resistant myeloma cells in comparison with parental cells, and that high expression of CD47 detected by immunohistochemistry is associated with shorter progression free and overall survivals in multiple myeloma patients. We show that miR-155 is expressed at low levels in drug resistant myeloma cells and is a direct regulator of CD47 through its 3'UTR. Furthermore, low miR-155 levels are associated with advanced stages of disease. MiR-155 overexpression suppressed CD47 expression on myeloma cell surface, leading to induction of phagocytosis of myeloma cells by macrophages and inhibition of tumor growth. MiR-155 overexpression also re-sensitized drug-resistant myeloma cells to bortezomib leading to cell death through targeting TNFAIP8, a negative mediator of apoptosis in vitro and in vivo. Thus, miR-155 mimics may serve as a promising new therapeutic modality by promoting phagocytosis and inducing apoptosis in patients with refractory/relapsed multiple myeloma

Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study

AbstractThis first prospective phase 2 study of single-agent bortezomib in relapsed primary systemic AL amyloidosis evaluated the recommended (maximum planned) doses identified in phase 1 testing (1.6 mg/m2 once weekly [days 1, 8, 15, and 22; 35-day cycles]; 1.3 mg/m2 twice weekly [days 1, 4, 8, and 11; 21-day cycles]). Among all 70 patients enrolled in the study, 44% had ≥ 3 organs involved, including 73% and 56% with renal and cardiac involvement. In the 1.6 mg/m2 once-weekly and 1.3 mg/m2 twice-weekly groups, the hematologic response rate was 68.8% and 66.7% (37.5% and 24.2% complete responses, respectively); median time to first/best response was 2.1/3.2 and 0.7/1.2 months, and 78.8% and 75.5% had response durations of ≥ 1 year, respectively. One-year hematologic progression-free rates were 72.2% and 74.6%, and 1-year survival rates were 93.8% and 84.0%, respectively. Outcomes appeared similar in patients with cardiac involvement. Among all 70 patients, organ responses included 29% renal and 13% cardiac responses. Rates of grade ≥ 3 toxicities (79% vs 50%) and discontinuations/dose reductions (38%/53% vs 28%/22%) resulting from toxicities appeared higher with 1.3 mg/m2 twice-weekly versus 1.6 mg/m2 once-weekly dosing. Both bortezomib dose schedules represent active, well-tolerated regimens in relapsed AL amyloidosis. This study was registered at www.clinicaltrials.gov as #NCT00298766

Daratumumab for patients with myeloma with early or late relapse after initial therapy:subgroup analysis of CASTOR and POLLUX

High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities, but patients who relapse early after initial therapy are considered a functional high-risk group. In the phase 3 CASTOR and POLLUX studies, daratumumab plus bortezomib/dexamethasone (D-Vd) or lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (≥CR) and minimal residual disease (MRD) negativity vs that with Vd/Rd alone in relapsed/refractory MM. Post hoc analyses of CASTOR and POLLUX evaluated patient subgroups with 1 prior line of therapy based on timing of progression/relapse (early or late) after initiation of first line of therapy. PFS consistently favored the daratumumab-containing regimens across subgroups using both a 24- and 18-month early-relapse cutoff. In the CASTOR/POLLUX pooled data set, daratumumab reduced the risk of disease progression or death by 65% (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.26-0.48; P &lt; .0001) in the early-relapse (&lt;24 months) subgroup and by 65% (HR, 0.35; 95% CI, 0.26-0.47; P &lt; .0001) in the late-relapse (≥24 months) subgroup. OS also favored the daratumumab-containing regimens in both the early-relapse (HR, 0.62; 95% CI, 0.45-0.86; P = .0036) and late-relapse (HR, 0.67; 95% CI, 0.48-0.93; P = .0183) subgroups in the pooled population using a 24-month cutoff. Rates of ≥CR and MRD negativity (10-5) were higher with daratumumab vs control, regardless of progression/relapse timing. Although daratumumab is unable to fully overcome the adverse prognosis of early relapse, our results support the use of daratumumab for patients with 1 prior line of therapy, including for those who progress/relapse early after initial therapy and are considered to have functional high-risk MM.</p

Daratumumab for patients with myeloma with early or late relapse after initial therapy:subgroup analysis of CASTOR and POLLUX

High-risk multiple myeloma (MM) is often defined based on cytogenetic abnormalities, but patients who relapse early after initial therapy are considered a functional high-risk group. In the phase 3 CASTOR and POLLUX studies, daratumumab plus bortezomib/dexamethasone (D-Vd) or lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS), regardless of cytogenetic risk, and achieved higher rates of complete response or better (≥CR) and minimal residual disease (MRD) negativity vs that with Vd/Rd alone in relapsed/refractory MM. Post hoc analyses of CASTOR and POLLUX evaluated patient subgroups with 1 prior line of therapy based on timing of progression/relapse (early or late) after initiation of first line of therapy. PFS consistently favored the daratumumab-containing regimens across subgroups using both a 24- and 18-month early-relapse cutoff. In the CASTOR/POLLUX pooled data set, daratumumab reduced the risk of disease progression or death by 65% (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.26-0.48; P &lt; .0001) in the early-relapse (&lt;24 months) subgroup and by 65% (HR, 0.35; 95% CI, 0.26-0.47; P &lt; .0001) in the late-relapse (≥24 months) subgroup. OS also favored the daratumumab-containing regimens in both the early-relapse (HR, 0.62; 95% CI, 0.45-0.86; P = .0036) and late-relapse (HR, 0.67; 95% CI, 0.48-0.93; P = .0183) subgroups in the pooled population using a 24-month cutoff. Rates of ≥CR and MRD negativity (10-5) were higher with daratumumab vs control, regardless of progression/relapse timing. Although daratumumab is unable to fully overcome the adverse prognosis of early relapse, our results support the use of daratumumab for patients with 1 prior line of therapy, including for those who progress/relapse early after initial therapy and are considered to have functional high-risk MM.</p