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There has always been something of the monster baked into the comic book superhero's DNA. Whether it pertains to the reality-bending powers of superhero soaring through the air, seeing through walls, setting her body aflame or altering her size, or by the more Gothic literary antecedents and 'science gone amok' themes constitutive of their origin stories, the comic book superhero treads a fine line between saviour and monster, as often evinced in the oscillating reactions of approbation and fear displayed by the diegetic public's reaction to them. Marvel Zombies, Marvel Comics' commercially successful depiction of its beloved superheroes as ravenous, flesh-eating cannibals, expresses one of the more recent and unsettling throwbacks to the monstrous origins and nature of the Marvel superhero. Employing Jeffrey Jerome Cohen's methodology of reading culture from the figure of the monster, this article proposes to explore Marvel Zombies as an indictment and parodic criticism of the Marvel Superhero. Just as the double is, per Sigmund Freud's psychoanalytic approach, an uncanny reminder of repressed truths and desires, so too does the decaying Marvel Zombie function as the uncanny doppelganger of the Marvel superhero, revealing the stagnant character development at its rotten core. [ABSTRACT FROM AUTHOR]

In this investigation, we tested hypotheses concerning how external validity, in relation to leadership and teamwork, was affected as participants moved from organizational to academic settings. Participants consisted of working business students (N = 159) from two countries, Peru and the United States, who adopted leader/teammate roles across settings. Results indicated that (a) transactional leadership and teamwork behavior demonstrated in organizational contexts were predictive of similar behavior in academic contexts, (b) the cultural setting of the study moderates the carry over effect of teamwork and leadership behavior from organizations to laboratories, and (c) for several leadership and teamwork behaviors, role identity and self-awareness incrementally added to the prediction of similar behaviors in academic contexts. We discuss the implications of our findings for enhancing the external validity of laboratory studies in applied psychology and for instruction of teamwork and leadership in academe. [ABSTRACT FROM AUTHOR]

A variety of collective phenomena are understood to exist to the extent that workers agree on their perceptions of the phenomena, such as perceptions of their organization's climate or perceptions of their team's mental model. Researchers conducting group-level studies of such phenomena measure individuals' perceptions via surveys and then aggregate data to the group level if the mean within-group agreement for a sample of groups is sufficiently high. Despite this widespread practice, we know little about the factors potentially affecting mean within-group agreement. Here, focusing on work climate, we report an investigation of a number of expected contextual (social interaction) and methodological predictors of mean rWG, a common statistic for judging within-group agreement in applied psychology and management research. We used the novel approach of meta-CART, which allowed us to assess the relative importance and possible interactions of the predictor variables. Notably, mean rWG values are driven by both contextual (average number of individuals per group and cultural individualism-collectivism) and methodological factors (the number of items in a scale and scale reliability). Our findings are largely consistent with expectations concerning how social interaction affects within-group agreement and psychometric arguments regarding why adding more items to a scale will not necessarily increase the magnitude of an index based on a Spearman-Brown "stepped-up correction." We discuss the key insights from our results, which are relevant to the study of multilevel phenomena relying on the aggregation of individual-level data and informative for how meta-analytic researchers can simultaneously examine multiple moderator variables. [ABSTRACT FROM AUTHOR]

(1) Background: In this case study, we examined the safety-training-related experiences of individuals from six racial-ethnic groups (Asians (Vietnamese), Blacks, Hispanics, Isleños, Native Americans, and Whites) involved in the cleanup of the Deepwater Horizon oil spill. (2) Methods: We assessed, via a survey, 495 disaster response trainees' reactions to the design and delivery of training, learning, safety performance, and injury and illness experience. (3) Results: Our results showed statistically significant racial-ethnic group differences with respect to reactions to training, components of learning (i.e., cognitive, skill, and affective), and safety performance (i.e., use of personal protective equipment, engaging in safe work practices, communicating of safety information, and exercising employee rights and responsibilities). In general, Asians and Isleños group members had lower reactions to training, self-reported learning, and safety performance. Additionally, we found that the safety climate interacted with learning to positively affect safety performance. (4) Conclusions: We discuss the implications of our findings for improving the quality of safety training in relation to addressing language and literacy concerns, developing training that is useful and engaging for volunteer and other cleanup workers from the contaminated region, and promoting a positive safety climate to enhance training transfer. [ABSTRACT FROM AUTHOR]

• Professional truck drivers' safety performance is captured by a six-factor model. • Compliance and communication factors are important predictors of hard braking. • General safety performance factors generalize to truck driver safety performance. In this investigation involving 227 lone professional truck drivers from a national transportation company in a low and moderate-income country (LMIC), Colombia, a multidimensional model of drivers' safety performance and expectations concerning how safety performance dimensions would predict hard braking were evaluated. The results supported a multidimensional conceptualization of professional truck drivers' safety performance, with factors aligned with confirmed general safety performance factors and occupation-specific factors. Furthermore, results supported the expectation that the dimensions associated with communicating safety information and complying with laws and regulations would predict hard braking over and above less conceptually relevant safety performance dimensions such as using personal protective equipment and preparing to drive, safety climate, and region of operation. Notably, a dimension of safety performance expected to promote workplace safety, the communication of health and safety information, was associated with increased hard braking. We discuss the implications of a multidimensional conceptualization and measure of safety performance for studying workplace safety for professional truck drivers in Colombian organizations and beyond. [ABSTRACT FROM AUTHOR]

ABSTRACT Chronic myelogenous leukemia (CML) is a rare disease in children for which pediatric evidence-based guidelines are lacking. We designed an anonymous survey for practicing pediatric oncologists and bone marrow transplantation (BMT) physicians to assess their willingness to recommend BMT for a patient with CML based on various clinical scenarios. A total of 274 physicians responded to the survey (13.4% response rate). Nearly all pediatric oncologists and BMT physicians recommended against BMT at time of diagnosis of CML in the chronic phase, with only 8.0% and 1.9% recommending BMT if a matched sibling donor (MSD) and a matched unrelated donor (MUD), respectively, was available. Similarly, after a first poor response to tyrosine kinase inhibitor (TKI) therapy or hematologic relapse, physicians continued to recommend against BMT (39.5% and 23.3% recommended BMT in patients with a matched sibling donor and matched unrelated donor, respectively). However, 81.7% and 69.8% of respondents would recommend BMT after 2 hematologic relapses on TKI therapy, if an MSD and an MUD, respectively, were available. In addition, there was great interest in developing a clinical trial evaluating the safety and efficacy of stopping TKIs in children with CML who achieve and maintain a deep molecular response, with 86.7% of respondents stating they would offer such a trial to their pediatric patients. This survey highlights the need for evidence-based, pediatric-specific guidelines for the management of children and adolescents with CML. [ABSTRACT FROM AUTHOR]

PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children’s Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5.4% (n = 482/8981) compared to 3.2% for IV (n = 245/7553) (p < .0001). If only the second and third doses of pegaspargase were analyzed, where the majority of grade ≥3 HSRs occur, the rate following IM injection was 10.1% (n = 459/4534) compared to 5.0% (n = 222/4443) for IV (p < .0001). On standardized treatment protocols conducted by the COG during 2003-2015, grade ≥3 HSR rates to pegaspargase occurred less frequently with IV infusion than IM injection. [ABSTRACT FROM AUTHOR]

Background: Children, adolescents, and young adults with very high-risk (VHR) B acute lymphoblastic leukemia (B-ALL) have poor outcomes, and novel therapies are needed for this subgroup. The AALL1131 study evaluated postinduction therapy using cyclophosphamide (CPM), etoposide (ETOP), and clofarabine (CLOF) for patients with VHR B-ALL.Methods: Patients who were 1 to 30 years old and had VHR B-ALL received modified Berlin-Frankfurt-Münster therapy after induction and were randomized to 1) CPM, cytarabine, mercaptopurine, vincristine (VCR), and pegaspargase (control arm), 2) CPM, ETOP, VCR, and pegaspargase (experimental arm 1), or 3) CPM, ETOP, CLOF (30 mg/m2 /d × 5), VCR, and pegaspargase (experimental arm 2) during the second half of consolidation and delayed intensification.Results: The rates of grade 4/5 infections and grade 3/4 pancreatitis were significantly increased in experimental arm 2. The dose of CLOF was, therefore, reduced to 20 mg/m2 /d × 5, and myeloid growth factor was required after CLOF administration. Despite these changes, 4 of 39 patients (10.3%) developed grade 4 infections, with 1 of these patients developing a grade 5 acute kidney injury attributed to CLOF, whereas only 1 of 46 patients (2.2%) in experimental arm 1 developed grade 4 infections, and there were no grade 4/5 infections in the control arm (n = 20). Four patients in experimental arm 2 had prolonged cytopenias for >60 days, whereas none did in the control arm or experimental arm 1. Counts failed to recover for 2 of these patients, one having a grade 5 acute kidney injury and the other removed from protocol therapy; both events occurred 92 days after the start of consolidation part 2.Conclusions: In AALL1131, CLOF, administered with CPM and ETOP, was associated with unacceptable toxicity. Cancer 2018;124:1150-9. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

During the 2016 Therapeutic Advances for Childhood Leukemia & Lymphoma (TACL) Consortium investigators' meeting (Los Angeles, CA), a Biology Working Group was established to support the consortium's mission of developing innovative therapies for currently incurable childhood leukemias and lymphomas. The charge of the Biology Working Group was to address howTACL could advance biological investigations of pediatric relapsed/refractory hematologic malignancies while undertaking forward-looking therapeutic trials. To this end, the TACL Biology Committee was established to provide the scientific platform needed to further develop preclinical and translational studies that will advance the understanding and treatment of relapsed and refractory disease. The Biology Committee will focus on ensuring state-of-the-art studies that address biological components of early phase clinical trials, and developing a central biology bank of materials from these early phase trials for interrogations into the mechanisms of disease resistance. [ABSTRACT FROM AUTHOR]

Asparaginase is a key component of therapy for acute lymphoblastic leukemia (ALL). Traditionally, asparaginase was administered intramuscularly but is now commonly given intravenously. Although intravenous administration is less painful, it can be challenging to differentiate hypersensitivity versus infusion-related reactions. The ability to distinguish between asparaginase-mediated reactions is critical to ensure optimal asparaginase treatment. In this paper, we will review the differences in pharmacokinetics and toxicities, when asparaginase is administered intravenously versus intramuscularly in pediatric patients with ALL. Differences between antibody-mediated hypersensitivity events and nonantibody-mediated infusion reactions will be addressed to assist practitioners in distinguishing between these clinically similar asparaginase-associated toxicities. [ABSTRACT FROM AUTHOR]

Supramolecular construction strategies have overwhelmingly relied on the principles of thermodynamic control. While this approach has yielded an incredibly diverse and striking collection of ensembles, there are downsides, most obviously the necessity to trade-off reversibility against structural integrity. Herein we describe an alternative AG "assembly-followed-by-fixing" approach that possesses the high-yielding, atom-efficient advantages of reversible self- assembly reactions, yet gives structures that possess a covalent-like level of kinetic robustness. We have chosen to exemplify these principles in the preparation of a series of M2L3 helicates and M4L6 tetrahedra. While the rigidity of various bis(bidentate) ligands causes the larger species to be energetically preferred, we are able to freeze the self-assembly process under "non-ambient" conditions, to selectivity give the disfavored M2L3 helicates. We also demonstrate "kinetic-stimuli" (redox and light)-induced switching between architectures, notably reconstituting the lower energy tetrahedra into highly distorted helicates. [ABSTRACT FROM AUTHOR]

Survival for children with relapsed T cell acute lymphoblastic leukemia (T-ALL) is poor when treated with chemotherapy alone, and outcomes after allogeneic hematopoietic cell transplantation (HCT) is not well described. Two hundred twenty-nine children with T-ALL in second complete remission (CR2) received an HCT after myeloablative conditioning between 2000 and 2011 and were reported to the Center for International Blood and Marrow Transplant Research. Median age was 10 years (range, 2 to 18). Donor source was umbilical cord blood (26%), matched sibling bone marrow (38%), or unrelated bone marrow/peripheral blood (36%). Acute (grades II to IV) and chronic graft-versus-host disease occurred in, respectively, 35% (95% confidence interval [CI], 27% to 45%) and 26% (95% CI, 20% to 33%) of patients. Transplant-related mortality at day 100 and 3-year relapse rates were 13% (95% CI, 9% to 18%) and 30% (95% CI, 24% to 37%), respectively. Three-year overall survival and disease-free survival rates were 48% (95% CI, 41% to 55%) and 46% (95% CI, 39% to 52%), respectively. In multivariate analysis, patients with bone marrow relapse, with or without concurrent extramedullary relapse before HCT, were most likely to relapse (hazard ratio, 3.94; P = .005) as compared with isolated extramedullary disease. In conclusion, HCT for pediatric T-ALL in CR2 demonstrates reasonable and durable outcomes, and consideration for HCT is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Despite remission rates of approximately 85% for children diagnosed with acute myeloid leukemia (AML), greater than 40% will die from relapsed disease. Patients with poor-risk molecular/cytogenetics and/or inadequate response to up-front therapy are typically considered high-risk (HR) and historically have poor outcomes with chemotherapy alone. We investigated whether allogeneic hematopoietic cell transplantation (allo-HCT) with best available donor in first remission (CR1) would abrogate the poor outcomes associated with HR AML in children and young adults treated with chemotherapy. We reviewed the outcomes of 50 consecutive children and young adults (ages 0 to 30 years) with AML who received a myeloablative allo-HCT between 2001 and 2010. Thirty-six patients (72%) were HR, defined as having FLT3-ITD mutations, 11q23 MLL rearrangements, chromosome 5 or 7 abnormalities, induction failure, and/or having persistent disease. The majority of patients received cyclophosphamide and total body irradiation conditioning, and graft-versus-host-disease (GVHD) prophylaxis was cyclosporine based. Transplantation outcomes for HR patients were compared to standard-risk patients, with no significant differences observed in overall survival (72% versus 78%, P = .72), leukemia-free survival (69% versus 79%, P = .62), relapse (11% versus 7%, P = .71), or treatment-related mortality (17% versus 14%, P = .89). Children and young adults with HR-AML have comparable outcomes to standard-risk patients following allo-HCT in CR1. [Copyright &y& Elsevier]

Abstract: Risk-adapted therapy has been the cornerstone of treatment for pediatric B precursor acute lymphoblastic leukemia (B-ALL). Recently, age ≥13 years at diagnosis has been identified as a very high-risk feature for chemotherapy treated pediatric patients with B-ALL. Whether age at time of transplantation is associated with poor outcomes in adolescents and young adults (AYA) is unknown. We hypothesized that AYA receiving allogeneic hematopoietic cell transplantation (allo-HCT) would have greater relapse and inferior survival compared with children age <13 years. We reviewed the outcomes in 136 consecutive patients (age 0-30 years) with B-ALL who underwent myeloablative allo-HCT at our institution, including 79 children age <13 years (58%) and 57 AYA age 13-30 years (42%). Overall survival at 5 years was significantly lower in the AYA group (hazard ratio, 1.74; 95% confidence interval [CI], 1.04-2.95; P = .03). In addition, the AYA patients had a greater risk of transplantation-related mortality at 1 year (hazard ratio, 2.23; 95% CI, 1.01-4.90; P = .05), but no difference in relapse (relative risk, 0.85; 95% CI, 0.41-1.76; P = .66). Based on this analysis, AYA patients undergoing allo-HCT for B-ALL have significantly inferior survival and greater transplantation-related mortality compared with children age <13 years, but no difference in relapse, suggesting that allo-HCT may overcome relapse in AYA. Further improvements in peritransplantation care are needed to limit complications in AYA patients. [Copyright &y& Elsevier]

Data on pretransplantation minimal residual disease (MRD) and outcomes of umbilical cord blood transplantation (UCBT) are limited. Out of the 143 patients with acute lymphoblastic leukemia (ALL) who underwent UCBT at the University of Minnesota between 2004 and 2010, we evaluated 86 patients with available MRD assessment data by 4- and 8-color flow cytometry analysis immediately before transplantation. Ten patients (11.6%) were MRD-positive, and 76 were MRD-negative (88.4%). Most of the patients (82%) received myeloablative conditioning. GVHD prophylaxis consisted of cyclosporine and mycophenolate mofetil. In multivariate analysis, age, disease status (complete remission [CR] 1 versus CR2/CR3), disease group (precursor B cell ALL versus Philadelphia chromosome–positive ALL versus T cell ALL), and time to transplantation had no impact on relapse. Patients with MRD before UCBT had a greater incidence of relapse at 2 years (relapse rate, 30%; 95% confidence interval [CI], 4%-56%) and lower 3-year disease-free survival (30%; 95% CI, 7%-58%) compared with those without MRD (relapse rate, 16%; 95% CI, 8%-25%; P = .05; disease-free survival, 55%; 95% CI, 43%-66%; P = .02). Our data suggest that in patients with ALL, achieving an MRD-negative state before UCBT improves outcomes. [Copyright &y& Elsevier]

Rapid lymphocyte recovery after bone marrow or peripheral blood transplantation is associated with improved survival. However, the impact of early lymphocyte recovery has not been examined after umbilical cord blood transplant (UCBT). We evaluated lymphocyte recovery in 360 consecutive patients with hematologic malignancy that underwent UCBT between 2001 and 2007. Uniform myeloablative (MA), reduced intensity conditioning (RIC) and graft-versus-host disease prophylaxis regimens were used. In multivariate analysis, an absolute leukocyte count (ALC) >200 × 106/L at day 30 (n = 73) after MA conditioning was associated with superior 2-year overall survival (OS) (73% versus 61%; P = .02) (relative risk [RR]: 2.29; 95% confidence interval [CI]: 1.15-4.56), progression-free survival (PFS) (68% versus 54%; P = .05) (RR: 1.96; 95% CI: 0.99-3.86) and less transplant-related mortality (8% versus 28%, P < .01) (RR: 4.38; 95% CI: 1.65-11.60) compared to ≤200 × 106/L (n = 43). Similarly, an ALC >200 × 106/L at day 42 (n = 105) after RIC was associated with superior 2-year OS (59% versus 41%, P < .01) (RR: 2.10; 95% CI: 1.3-3.41) and PFS (46% versus 36%, P = .05) (RR: 1.58; 95% CI: 1.01-2.49) compared to ≤200 × 106/L (n = 55). There was no significant relationship between ALC and relapse. Rapid lymphocyte recovery early after UCBT predicts better survival in patients with hematologic malignancies. [ABSTRACT FROM AUTHOR]

The current study tested a model of group effectiveness in which emotional conflict, negative affective tone in groups, and group mean agreeableness were proposed as key antecedent variables. Data collected from 84 project groups supported the proposition that group-level agreeableness was significantly related with emotional conflict, and that emotional conflict indirectly affects group outcomes through group-level negative affective tone and contextual-discretionary behaviors, as opposed to task-related behaviors. Findings are discussed in terms of how group members' personality foster emotional conflict in groups and the implications of these findings for group effectiveness research as well as the management of project groups. [ABSTRACT FROM AUTHOR]

Abstract: Since 1989, researchers with the Department of Primary Industries and Fisheries (DPI&F) in Queensland, Australia, have successfully used controlled low-water exchange green-water cultures to rear the larvae of estuarine fishes and crustaceans through to metamorphosis. High survivals and excellent fry condition have been achieved for several commercially important endemic species produced for various projects. They include barramundi or sea bass, Lates calcarifer, Australian bass, Macquaria novemaculeata, dusky flathead, Platycephalus fuscus, sand whiting, Sillago ciliata, red sea bream or snapper, Pagrus auratus, banana prawn, Fenneropenaeus merguiensis, and others. The consistent success of our standardised and relatively simple approach at different localities has led to it being incorporated into general fingerling production practices at several establishments in Australia. Although post-metamorphosis rearing methods have differed for each species investigated, due to various biological and behavioural traits and project requirements, these larval rearing methods have been successful with few species-specific modifications. Initially modelled on the Taiwanese approach to rearing Penaeids in aerated low-water exchange cultures, the approach similarly appears to rely on a beneficial assemblage of micro-organisms. Conceptually, these micro-organisms may include a mixture of the air-borne primary invaders of pure phytoplankton cultures when exposed to outdoor conditions. Whilst this would vary with different sites, our experiences with these methods have consistently been favourable. Mass microalgal cultures with eco-physiological youth are used to regularly augment larval fish cultures so that rearing conditions simulate an exponential growth-phase microalgal bloom. Moderate to heavy aeration prevents settlement of particulate matter and encourages aerobic bacterial decomposition of wastes. The green-water larval rearing approach described herein has demonstrated high practical utility in research and commercial applications, and has greatly simplified marine finfish hatchery operations whilst generally lifting production capacities for metamorphosed fry in Australia. Its potential uses in areas of aquaculture other than larviculture are also discussed. [Copyright &y& Elsevier]

Objectives. We sought to determine the relative effectiveness of different methods of worker safety and health training aimed at improving safety knowledge and performance and reducing negative outcomes (accidents, illnesses, and injuries). Methods. Ninety-five quasi-experimental studies (n = 20991) were included in the analysis. Three types of intervention methods were distinguished on the basis of learners' participation in the training process: least engaging (lecture, pamphlets, videos), moderately engaging (programmed instruction, feedback interventions), and most engaging (training in behavioral modeling, hands-on training). Results. As training methods became more engaging (i.e., requiring trainees' active participation), workers demonstrated greater knowledge acquisition, and reductions were seen in accidents, illnesses, and injuries. All methods of training produced meaningful behavioral performance improvements. Conclusions. Training involving behavioral modeling, a substantial amount of practice, and dialogue is generally more effective than other methods of safety and health training. The present findings challenge the current emphasis on more passive computer-based and distance training methods within the public health workforce. [ABSTRACT FROM AUTHOR]

We tested competing models of group effectiveness for 71 distance collaboration groups (equipos) comprised of 200 Mexican business students solving cases via electronic communication in a virtual education program. For one model, task cohesion was specified as an exogenous variable leading to collective efficacy and, ultimately, group effectiveness; whereas, in the second model, task cohesion was specified as a mediator of the relationship between collective efficacy and group effectiveness. The results provided support for the model where task cohesion mediated the relationship between collective efficacy and group effectiveness and where group behavioral performance (facilitating team and peer performance) had a direct effect on group effectiveness. The implications of these findings for the study and management of distance collaboration groups are discussed. [Copyright &y& Elsevier]

A unique case of the diagnosis and treatment of a ruptured cerebral aneurysm in a 5-year-old male is presented. The child presented with subarachnoid hemorrhage, and initial CT imaging indicated a right posterior communicating artery aneurysm. Cerebral angiography and MRI/MRA were normal. Repeat cerebral angiogram 3 weeks later was also normal. Sixteen months later, an angiogram was performed to evaluate a subtle carotid bruit found on exam. A carotid bifurcation aneurysm pointing inferior and posterior was found. Craniotomy to clip the aneurysm was performed, and marked adherent gliosis around the lesion was found, supporting the fact that this was the causal lesion of his bleed in the past. Albeit a single case report, it underscores the need for very long-term follow-up and evaluation of idiopathic pediatric subarachnoid hemorrhage.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Examines the effect of negative affectivity on the relationship between self-reports of exercise and strain in a sample of 128 government employees. Objective sick leave as an indicator of strain; Correlations between exercise and strain.

Presents information on a study which examined the effects of rater age, age salience and job-relevant information on manager's ratings of an older or younger hypothetical applicant's interpersonal skills, economic worth and likelihood of being interviewed. Methodology; Effects of target age on dependent variables; Results of the experiment.

Examines the effect of transforming actual skewed variables toward symmetry on the intercorrelations among the transformed variables. Increase in average correlations; Correcting skew's increased power; Potential difficulties associated with correction of skew in correlational research.

Examines the relationship between the degree of voluntary participation in quality circles, employee work climate perceptions, and the quality circle outcome measures among federal government employees. Relationship of the degree of participation in quality circles with the quality circle guidelines; Effects of economic gains on the quality circle guidelines.

Abstract: A non-acidic procedure for the preparation of 3-aminoindazoles and 3-amino-7-azaindazoles from 2-fluoroaryl carboxylic acids is reported. The synthesis starts from readily available starting materials and uses mild and practical reaction conditions in a three-step overall procedure. Products were isolated for a number of examples, but yields varied significantly depending on electronic nature of the substituents. [Copyright &y& Elsevier]

The author reflects on the presence of minimal residual disease in patients with acute myeloid leukemia (AML). He examines the relapse of the disease after induction therapy or before stem-cell transplantation. The author cites the use of stem-cell transplantation for the patients with high-risk AML while chemotherapy for the patients with low-risk AML.

Pays tribute to William P. Dunlap, a scholar in the field of research methodology and statistics, who died on February 28, 2002. Characteristics as a scholar; Educational and professional background; His contributions to the field of research methodology and statistics.

Objective: To compare Medicare-related costs and service utilisation of people with diagnosed diabetes, asthma or chronic obstructive pulmonary disease (COPD) to those who were previously undiagnosed, and those without these conditions. Design, setting and participants: Representative cross-sectional study of people (18+ years) living in the north-west area of Adelaide. Participants were recruited by telephone interviews. Biomedical and self-report data for 2352 participants were linked to Medicare Australia Medicare Benefits Schedule (MBS) data from 1997 to 2002. Main outcome measures: Mean number and cost (benefit paid) of MBS services for people with diagnosed and previously undiagnosed diabetes, asthma, and COPD, and those without these conditions. Results: Mean (± SD) MBS costs were significantly greater for people diagnosed with diabetes ($4205 ± 2596), asthma ($3307 ± 2542), or COPD ($3779 ± 2529) than for those without these conditions. MBS costs for people with asthma or COPD that had not yet been diagnosed were also significantly higher than for those without these conditions, although this was inconsistent across financial years. Conclusions: Diabetes, asthma, and COPD are costly conditions in terms of health service use. Costs associated with undiagnosed asthma and COPD are similar to their diagnosed states. Prevention of progression along each chronic disease continuum is likely to reduce costs. [ABSTRACT FROM AUTHOR]

Early after umbilical cord blood transplantation, patients show marked differences in bone marrow (BM) hematogone percentages. Little is known about whether these differences are clinically relevant. We hypothesized that early recovery of hematogones may be associated with improved transplantation outcomes. BM aspirates were assessed from 88 patients with acute myeloid leukemia by two independent reviewers at day 21 and 100 after umbilical cord blood transplantation. Interobserver variability for BM hematogone percentages at these time points showed correlation coefficients of 0.83 and 0.98, respectively (P ≤ .01 for both). A high percentage of hematogones at day 21 was associated with less acute graft-versus-host disease grade 3 to 4 (P = .01). At day 100, a high percentage of BM hematogones was associated with improved overall survival (P = .02) and lower treatment-related mortality (P ≤ .01). This study shows that BM hematogone percentages may be useful prognostic indicators in patients with acute myeloid leukemia after umbilical cord blood transplantation and should be routinely reported in BM differential counts. [ABSTRACT FROM AUTHOR]

Several investigators have observed a discrepancy in electrospray response of complementary strands from denatured DNA, which has been attributed to the difference in hydrophobicity between the two strands; the more hydrophobic species tend to have higher ion abundances. The implementation of a heated electrospray source has allowed us to “level” the electrospray response for two equimolar complementary strands with different hydrophobicities. As the temperature was increased, the ratio of ion abundances of the less hydrophobic noncoding strand to the more hydrophobic coding strand approached unity. Furthermore, the heated electrospray source was used to denature amplicons containing 7-deaza purines, which can be used to facilitate sequencing by mass spectrometry. [Copyright &y& Elsevier]

Background: Pegaspargase (PEG‐ASP) is an integral component of therapy for acute lymphoblastic leukemia (ALL) but is associated with hepatotoxicity that may delay or limit future therapy. Obese and adolescent and young adult (AYA) patients are at high risk. Levocarnitine has been described as potentially beneficial for the treatment or prevention of PEG‐ASP‐associated hepatotoxicity. Methods: We collected data for patients age ≥10 years who received levocarnitine during induction therapy for ALL, compared to a similar patient cohort who did not receive levocarnitine. The primary endpoint was conjugated bilirubin (c.bili) >3 mg/dl. Secondary endpoints were transaminases >10× the upper limit of normal and any Grade ≥3 hepatotoxicity. Results: Fifty‐two patients received levocarnitine for prophylaxis (n = 29) or rescue (n = 32) of hepatotoxicity. Compared to 109 patients without levocarnitine, more patients receiving levocarnitine were obese and/or older and had significantly higher values for some hepatotoxicity markers at diagnosis and after PEG‐ASP. Levocarnitine regimens varied widely; no adverse effects of levocarnitine were identified. Obesity and AYA status were associated with an increased risk of conjugated hyperbilirubinemia and severe transaminitis. Multivariable analysis identified a protective effect of levocarnitine on the development of c.bili >3 mg/dl (OR 0.12, p = 0.029). There was no difference between groups in CTCAE Grade ≥3 hepatotoxicity. C.bili >3 mg/dl during induction was associated with lower event‐free survival. Conclusions: This real‐world data on levocarnitine supplementation during ALL induction highlights the risk of PEG‐ASP‐associated hepatotoxicity in obese and AYA patients, and hepatotoxicity's potential impact on survival. Levocarnitine supplementation may be protective, but prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Summary: Ponatinib has proven to be effective in adults with Philadelphia chromosome‐positive leukaemias, but data in paediatrics are scarce. Among paediatric patients with chronic myeloid leukaemia (n = 9) or acute lymphoblastic leukaemia (n = 12) treated with varying doses of ponatinib in 13 centres, 71% showed a decrease in disease burden after a median of three months. Ponatinib was well tolerated, with grade 3 toxicities occurring in 29% of patients. Toxicities were similar to those reported in adults, with the exception of arterial thrombotic events, which were not observed. Ponatinib has a favourable safety profile in this paediatric cohort, but dose‐finding studies are needed. [ABSTRACT FROM AUTHOR]

Electronic pacemakers can treat electrical conduction disorders in hearts; however, they are invasive, bulky, and linked to increased incidence of infection at the tissue-device interface. Thus, researchers have looked to other more biocompatible methods for cardiac pacing or resynchronization, such as femtosecond infrared light pulsing, optogenetics, and polymer-based cardiac patches integrated with metal electrodes. Here we develop a biocompatible nongenetic approach for the optical modulation of cardiac cells and tissues. We demonstrate that a polymer-silicon nanowire composite mesh can be used to convert fast moving, lowradiance optical inputs into stimulatory signals in target cardiac cells. Our method allows for the stimulation of the cultured cardiomyocytes or ex vivo heart to beat at a higher target frequency. [ABSTRACT FROM AUTHOR]

Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy. Five of these patients were treated with levocarnitine with subsequent improvement of hyperbilirubinemia, while one patient was given levocarnitine prophylactically during induction and developed Grade 3 hyperbilirubinemia, but did not require therapy adjustments or delays. Increased awareness in the pediatric oncology community regarding asparaginase-associated hepatic toxicity and the potential role of levocarnitine in management is warranted. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the ability of decitabine in enhancing the chemosensitivity of the early precursor of T-cell acute lymphoblastic leukemia cells.

Whereas the improvement in outcome for children with acute lymphoblastic leukemia has been gratifying, the poor outcome of patients who relapse warrants novel treatment approaches. Previously, we identified a characteristic relapse-specific gene expression and methylation signature associated with chemoresistance using a large cohort of matched-diagnosis relapse samples. We hypothesized that "reversing" such a signature might restore chemosensitivity. In the present study, we demonstrate that the histone deacetylase inhibitor vorinostat not only reprograms the aberrant gene expression profile of relapsed blasts by epigenetic mechanisms, but is also synergistic when applied before chemotherapy in primary patient samples and leukemia cell lines. Furthermore, incorporation of the DNA methyltransferase inhibitor decitabine led to reexpression of genes shown to be preferentially methylated and silenced at relapse. Combination pretreatment with vorinostat and decitabine resulted in even greater cytotoxicity compared with each agent individually with chemotherapy. Our results indicate that acquisition of chemoresistance at relapse may be driven in part by epigenetic mechanisms. Incorporation of these targeted epigenetic agents to the standard chemotherapy backbone is a promising approach to the treatment of relapsed pediatric acute lymphoblastic leukemia. [ABSTRACT FROM AUTHOR]

Reduced-intensity conditioning regimens have been used extensively in adults with hematologic malignancies. To address whether this is a feasible approach for children with acute lymphoblastic leukemia, we evaluated transplant outcomes in 38 recipients transplanted from 1995-2005 for whom this was their first transplant. The median age at transplant was 12 years, and 47% had performance scores <90%. Disease status was first complete remission (CR) in 13%, ≥CR2 in 60% of patients, and 22% had active disease at transplantation. Matched related donors were available for a third of patients, about half of whom received bone marrow (BM) and the others, peripheral blood progenitor cells. Sixty percent of unrelated donor transplant recipients received peripheral blood progenitor cells. The day-100 probability of grade II-IV acute graft-versus-host disease was 37% and the 3-year probability of chronic graft-versus-host disease, 26%. At 3 years, the probability of treatment-related mortality was 40%, relapse 37%, and disease-free survival 30%. These data indicate long-term DFS can be achieved using reduced-intensity conditioning regimens in children with acute lymphoblastic leukemia. Given the relatively small cohort, these findings must be validated in a larger population. [ABSTRACT FROM AUTHOR]

Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) has rapidly established a prominent role in proteomics because of its unparalleled resolving power, sensitivity and ability to achieve high mass measurement accuracy (MMA) simultaneously. However, space-charge effects must be quantitatively, routinely, and confidently corrected because they are known to profoundly influence MMA. We argue that the most effective way to account for space-charge effects is to introduce an internal mass calibrant (IMC) using a dual electrospray ionization (ESI) source where the IMC is added from a separate ESI emitter. The major disadvantage of our initial dual ESI source to achieve high MMA, and arguably the only one, was the time required to switch between the analyte emitter and IMC emitter (i.e., >300 ms). While this "switching time" was acceptable for direct infusion experiments, it did not lend itself to high-throughput applications or when conducting on-line liquid separations. In this report, we completely redesigned the dual ESI source and demonstrate several key attributes. First, the new design allows for facile alignment of ESI emitters, undetectable vibration, and the ability to extend to multiple emitters. Second, the switching time was reduced to <50 ms, which allowed the analyte and IMC to be accumulated "simultaneously" in the external ion reservoir and injected as a single ion packet into the ion cyclotron resonance cell, eliminating the need for a separate accumulation and ion injection event for the IMC. Third, by using a high concentration of the IMC, the residence time on this emitter could be reduced to ∼80 ms, allowing for more time spent accumulating analyte ions of significantly lower concentration. Fourth, multiplexed on-line separations can be carried out providing increased throughput. Specifically, the new dual ESI source has demonstrated its ability to produce a stable ion current over a 45-min time period at 7 T resulting in... [ABSTRACT FROM AUTHOR]

The MCMI-III (Millon, Davis, & Millon, 1997) is a widely used measure of personality often used in inpatient psychiatric settings. Although patients in such settings often overreport or exaggerate their symptoms, relatively little is known about how such a response set presents on the validity indexes of the MCMI-III. In this study, we used a sample of 191 psychiatric inpatients and compared MCMI-III modifier indices (Disclosure, Desirability, and Debasement) with the validity measures (L, F, Fb, F(p), K, and F - K) of the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). In addition, the MCMI-III Disclosure Index (Scale X, which imposes a set cutoff score for invalidity due to overreport) was compared to several cutoff scores on the validity scales of the MMPI-2. Although the MCMI-III indexes generally performed as expected, the MCMI-III had a very high tolerance for overreport. When contrasted with MMPI-2 F scale, the MCMI-III Disclosure Index (which gauges overreport) remained valid until scores on MMPI-2 F scale approached a T score of 120. In addition, the Disclosure Index was at the upper end or slightly exceeded the highest recommended cutoff scores on all other MMPI-2 validity scales except F - K. Clinicians using the MCMI-III alone are cautioned to consider the high tolerance the MCMI-III has for overreport. [ABSTRACT FROM AUTHOR]