Secondary acute lymphoblastic leukemia is a distinct clinical entity with prognostic significance.

The effect of prior malignancy on the risk of developing, and prognosis of, acute lymphoblastic leukemia (ALL) is unknown. This observational study utilized the California Cancer Registry to estimate the risk of developing ALL after a prior malignancy using standardized incidence ratios (SIRs, 95% confidence intervals). ALL occurring after a malignancy with an SIR>1 (increased-risk (IR) malignancies) was considered secondary ALL (s-ALL). Adjusted hazard ratios (aHRs, 95% confidence intervals) compared the effect of s-ALL with de novo ALL on overall survival. A total of 14 481 patients with ALL were identified (1988-2012) and 382 (3%) had a known prior malignancy. Any prior malignancy predisposed patients to developing ALL: SIR 1.62 (1.45-1.79). Hematologic malignancies (SIR 5.57, 4.38-6.98) and IR-solid tumors (SIR 2.11, 1.73-2.54) increased the risk of developing ALL. s-ALL increased the risk of death compared with de novo ALL (aHR 1.38 (1.16-1.63)) and this effect was more pronounced among younger patients (age<40 years: aHR 4.80 (3.15-7.30); age⩾40 years: aHR 1.40 (1.16-1.69)) (interaction P<0.001). This population-based study demonstrates that s-ALL is a distinct entity that occurs after specific malignancies and carries a poor prognosis compared with de novo ALL, particularly among patients <40 years of age

Editorial: Immunogenicity of Proteins Used as Therapeutics

International audienc

Immunology of naturally transmissible tumours.

Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/imm.1237

Perturbations of nuclear C*-algebras

Kadison and Kastler introduced a natural metric on the collection of all C*-subalgebras of the bounded operators on a separable Hilbert space. They conjectured that sufficiently close algebras are unitarily conjugate. We establish this conjecture when one algebra is separable and nuclear. We also consider one-sided versions of these notions, and we obtain embeddings from certain near inclusions involving separable nuclear C*-algebras. At the end of the paper we demonstrate how our methods lead to improved characterisations of some of the types of algebras that are of current interest in the classification programme.Comment: 45 page

Development of a decision support tool to facilitate primary care management of patients with abnormal liver function tests without clinically apparent liver disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE)

Liver function tests (LFTs) are routinely performed in primary care, and are often the gateway to further invasive and/or expensive investigations. Little is known of the consequences in people with an initial abnormal liver function (ALF) test in primary care and with no obvious liver disease. Further investigations may be dangerous for the patient and expensive for Health Services. The aims of this study are to determine the natural history of abnormalities in LFTs before overt liver disease presents in the population and identify those who require minimal further investigations with the potential for reduction in NHS costs

Reliability and validity of three questionnaires measuring context-specific sedentary behaviour and associated correlates in adolescents, adults and older adults

BACKGROUND: Reliable and valid measures of total sedentary time, context-specific sedentary behaviour (SB) and its potential correlates are useful for the development of future interventions. The purpose was to examine test-retest reliability and criterion validity of three newly developed questionnaires on total sedentary time, context-specific SB and its potential correlates in adolescents, adults and older adults. METHODS: Reliability and validity was tested in six different samples of Flemish (Belgium) residents. For the reliability study, 20 adolescents, 22 adults and 20 older adults filled out the age-specific SB questionnaire twice. Test-retest reliability was analysed using Kappa coefficients, Intraclass Correlation Coefficients and/or percentage agreement, separately for the three age groups. For the validity study, data were retrieved from 62 adolescents, 33 adults and 33 older adults, with activPAL as criterion measure. Spearman correlations and Bland-Altman plots (or non-parametric approach) were used to analyse criterion validity, separately for the three age groups and for weekday, weekend day and average day. RESULTS: The test-retest reliability for self-reported total sedentary time indicated following values: ICC = 0.37-0.67 in adolescents; ICC = 0.73-0.77 in adults; ICC = 0.68-0.80 in older adults. Item-specific reliability results (e.g. context-specific SB and its potential correlates) showed good-to-excellent reliability in 67.94%, 68.90% and 66.38% of the items in adolescents, adults and older adults respectively. All items belonging to sedentary-related equipment and simultaneous SB showed good reliability. The sections of the questionnaire with lowest reliability were: context-specific SB (adolescents), potential correlates of computer use (adults) and potential correlates of motorized transport (older adults). Spearman correlations between self-reported total sedentary time and the activPAL were different for each age group: rho = 0.02-0.42 (adolescents), rho = 0.06-0.52 (adults), rho = 0.38-0.50 (older adults). Participants over-reported total sedentary time (except for weekend day in older adults) compared to the activPAL, for weekday, weekend day and average day respectively by +57.05%, +46.29%, +53.34% in adolescents; +40.40%, +19.15%, +32.89% in adults; +10.10%, -6.24%, +4.11% in older adults. CONCLUSIONS: The questionnaires showed acceptable test-retest reliability and criterion validity. However, over-reporting of total SB was noticeable in adolescents and adults. Nevertheless, these questionnaires will be useful in getting context-specific information on SB

‘Do i care?’ young adults' recalled experiences of early adolescent overweight and obesity: a qualitative study

<p>Objective: Individual behaviour change to reduce obesity requires awareness of, and concern about, weight. This paper therefore describes how young adults, known to have been overweight or obese during early adolescence, recalled early adolescent weight-related awareness and concerns. Associations between recalled concerns and weight-, health- and peer-related survey responses collected during adolescence are also examined.</p> <p>Design: Qualitative semi-structured interviews with young adults; data compared with responses to self-report questionnaires obtained in adolescence.</p> <p>Participants: A total of 35 participants, purposively sub-sampled at age 24 from a longitudinal study of a school year cohort, previously surveyed at ages 11, 13 and 15. Physical measures during previous surveys allowed identification of participants with a body mass index (BMI) indicative of overweight or obesity (based on British 1990 growth reference) during early adolescence. Overall, 26 had been obese, of whom 11 had BMI99.6th centile, whereas 9 had been overweight (BMI=95th–97.9th centile).</p> <p>Measures: Qualitative interview responses describing teenage life, with prompts for school-, social- and health-related concerns. Early adolescent self-report questionnaire data on weight-worries, self-esteem, friends and victimisation (closed questions).</p> <p>Results: Most, but not all recalled having been aware of their overweight. None referred to themselves as having been obese. None recalled weight-related health worries. Recollection of early adolescent obesity varied from major concerns impacting on much of an individual's life to almost no concern, with little relation to actual severity of overweight. Recalled concerns were not clearly patterned by gender, but young adult males recalling concerns had previously reported more worries about weight, lower self-esteem, fewer friends and more victimisation in early adolescence; no such pattern was seen among females. Conclusion: The popular image of the unhappy overweight teenager was not borne out. Many obese adolescents, although well aware of their overweight recalled neither major dissatisfaction nor concern. Weight-reduction behaviours are unlikely in such circumstances.</p&gt

Advances in Zero-Sum Dynamic Games

International audienceThe survey presents recent results in the theory of two-person zero-sum repeated games and their connections with differential and continuous-time games. The emphasis is made on the following(1) A general model allows to deal simultaneously with stochastic and informational aspects.(2) All evaluations of the stage payoffs can be covered in the same framework (and not only the usual Cesàro and Abel means).(3) The model in discrete time can be seen and analyzed as a discretization of a continuous time game. Moreover, tools and ideas from repeated games are very fruitful for continuous time games and vice versa.(4) Numerous important conjectures have been answered (some in the negative).(5) New tools and original models have been proposed. As a consequence, the field (discrete versus continuous time, stochastic versus incomplete information models) has a much more unified structure, and research is extremely active

Differentiation of Glioma and Radiation Injury in Rats Using In Vitro Produce Magnetically Labeled Cytotoxic T-Cells and MRI

A limitation with current imaging strategies of recurrent glioma undergoing radiotherapy is that tumor and radiation injury cannot be differentiated with post contrast CT or MRI, or with PET or other more complex parametric analyses of MRI data. We propose to address the imaging limitation building on emerging evidence indicating that effective therapy for recurrent glioma can be attained by sensitized T-cells following vaccination of primed dendritic cells (DCs). The purpose of this study was to determine whether cord blood T-cells can be sensitized against glioma cells (U-251) and if these sensitized cytotoxic T-cells (CTLs) can be used as cellular magnetic resonance imaging probes to identify and differentiate glioma from radiation necrosis in rodent models.Cord blood T and CD14+ cells were collected. Isolated CD14+ cells were then converted to dendritic cells (DCs), primed with glioma cell lysate and used to sensitize T-cells. Phenotypical expression of the generated DCs were analyzed to determine the expression level of CD14, CD86, CD83 and HLA-DR. Cells positive for CD25, CD4, CD8 were determined in generated CTLs. Specificity of cytotoxicity of the generated CTLs was also determined by lactate dehydrogenase (LDH) release assay. Secondary proliferation capacity of magnetically labeled and unlabeled CTLs was also determined. Generated CTLs were magnetically labeled and intravenously injected into glioma bearing animals that underwent MRI on days 3 and 7 post- injection. CTLs were also administered to animals with focal radiation injury to determine whether these CTLs accumulated non-specifically to the injury sites. Multi-echo T2- and T2*-weighted images were acquired and R2 and R2* maps created. Our method produced functional, sensitized CTLs that specifically induced U251 cell death in vitro. Both labeled and unlabeled CTLs proliferated equally after the secondary stimulation. There were significantly higher CD25 positive cells (p = <0.006) in CTLs. In addition, T2- and T2*-weighted MR images showed increased low signal intensity areas in animals that received labeled CTLs as compared to the images from animals that received control cells. Histological analysis confirmed the presence of iron positive cells in sites corresponding to MRI low signal intensity regions. Significant differences (p = <0.001) in tumor R2 and R2* values were observed among the groups of animals. Animals with radiation injury exhibited neither MRI hypointense areas nor presence of iron positive cells.Our results indicate that T-cells can be effectively sensitized by in vitro methods and used as cellular probes to identify and differentiate glioma from radiation necrosis