Neural network methods for one-to-many multi-valued mapping problems

An investigation of the applicability of neural network-based methods in predicting the values of multiple parameters, given the value of a single parameter within a particular problem domain is presented. In this context, the input parameter may be an important source of variation that is related with a complex mapping function to the remaining sources of variation within a multivariate distribution. The definition of the relationship between the variables of a multivariate distribution and a single source of variation allows the estimation of the values of multiple variables given the value of the single variable, addressing in that way an ill-conditioned one-to-many mapping problem. As part of our investigation, two problem domains are considered: predicting the values of individual stock shares, given the value of the general index, and predicting the grades received by high school pupils, given the grade for a single course or the average grade. With our work, the performance of standard neural network-based methods and in particular multilayer perceptrons (MLPs), radial basis functions (RBFs), mixture density networks (MDNs) and a latent variable method, the general topographic mapping (GTM), is compared. According to the results, MLPs and RBFs outperform MDNs and the GTM for these one-to-many mapping problems

‘Healthy Eating’ and Social Media Use

Orthorexia Nervosa (ON) describes a pathological, unhealthy fixation with eating healthy food. Research concerning the symptomatology of ON, and its prevalence in numerous samples, differs as there no official measures or clear diagnostic criteria exist for this fairly new affliction. Though research on the link between the epidemiology of ON and social media is gaining traction, published evidence is scarce. This study intends to further understand ON and its possible link to the use of social media, and specifically, to test the prevalence of ON in an opportunity sample with the use of two ON measures – the ORTO-15 and the Tereul Orthorexia Scale (TOS); to use and validate a new ON measure (TOS); to examine the relationship between ON and social media use, with a focus on Instagram users; and to further understand the participants’ interpretations of the possible link between eating patterns and social media use. This study uses a convergent design and a mixed methods approach, which employs both statistical and thematic analysis (TA) to evaluate the quantitative and qualitative data generated. Data from 201 participants suggested a high prevalence of ON across the sample, and the results also reinforced the validity of the TOS measure (α = .86). ORTO 15 scores showed significant differences between age groups, genders, and Instagram users and non-Instagram users. The TA generated three overall themes: ‘The Importance of Belonging’, ‘Health as Art’ and ‘Craving’. The high prevalence in the sample may have been a result of the researcher’s recruitment method, and the ON measures may have categorised individuals on non-medically prescribed diets as ‘orthorexic’. Both the quantitative and qualitative results offer evidence to support a possible link between ON and social media use, specifically Instagram. Further research should be done to establish official criteria and measures for ON and the effect of social media on eating patterns, and to investigate the notion of ‘healthism’

The Cost-effectiveness of Pixantrone for Third/Fourth-line Treatment of Aggressive Non-Hodgkin's Lymphoma

PURPOSE: Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long-term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed ≥ 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy. The objective of this study was to assess the health economic implications of pixantrone versus current clinical practice (CCP) in the United Kingdom for patients with multiply relapsed or refractory aNHL receiving their third or fourth line of treatment. METHODS: A semi-Markov partition model based on overall survival and PFS was developed to evaluate the lifetime clinical and economic impact of treatment of multiply relapsed or refractory aNHL with pixantrone versus CCP. The empirical overall survival and PFS data from the PIX301 trial were extrapolated to a lifetime horizon. Resource use was elicited from clinical experts, and unit costs and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom's National Health Service and personal social services. Outcomes evaluated were total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty around the results. FINDINGS: Pixantrone was estimated to increase life expectancy by a mean of 10.8 months per patient compared with CCP and a mean gain of 0.56 discounted QALYs. The increased health gains were associated with an increase in discounted costs of approximately £18,494 per patient. The incremental cost-effectiveness ratio of pixantrone versus CCP was £33,272 per QALY gained. Sensitivity and scenario analyses suggest that the incremental cost-effectiveness ratio was sensitive to uncertainty in the PFS and overall survival estimates and the utility values associated with each health state. IMPLICATIONS: Pixantrone may be considered both clinically effective and cost-effective for patients with multiply relapsed or refractory aNHL who currently have a high level of unmet need

Removing pose from face images

This paper proposes a novel approach to pose removal from face images based on the inherent symmetry that is present in faces. In order for face recognition systems and expression classification systems to operate optimally, subjects must look directly into the camera. The removal of pose from face images after their capture removes this restriction. To obtain a pose-removed face image, the frequency components at each position of the face image, obtained through a wavelet transformation, are examined. A cost function based on the symmetry of this wavelet transformed face image is minimized to achieve pose removal.Experimental results are presented that demonstrate that the proposed algorithm improves upon existing techniques in the literature

Optimized gene engineering of murine CAR-T cells reveals the beneficial effects of IL-15 coexpression.

Limited clinical benefit has been demonstrated for chimeric antigen receptor (CAR) therapy of solid tumors, but coengineering strategies to generate so-called fourth-generation (4G) CAR-T cells are advancing toward overcoming barriers in the tumor microenvironment (TME) for improved responses. In large part due to technical challenges, there are relatively few preclinical CAR therapy studies in immunocompetent, syngeneic tumor-bearing mice. Here, we describe optimized methods for the efficient retroviral transduction and expansion of murine T lymphocytes of a predominantly central memory T cell (TCM cell) phenotype. We present a bicistronic retroviral vector encoding both a tumor vasculature-targeted CAR and murine interleukin-15 (mIL-15), conferring enhanced effector functions, engraftment, tumor control, and TME reprogramming, including NK cell activation and reduced presence of M2 macrophages. The 4G-CAR-T cells coexpressing mIL-15 were further characterized by up-regulation of the antiapoptotic marker Bcl-2 and lower cell-surface expression of the inhibitory receptor PD-1. Overall, this work introduces robust tools for the development and evaluation of 4G-CAR-T cells in immunocompetent mice, an important step toward the acceleration of effective therapies reaching the clinic

CART cells are prone to Fas- and DR5-mediated cell death.

Adoptive transfer of T cells transduced with Chimeric Antigen Receptors (CAR) are now FDA-approved for the treatment of B-cell malignancies. Yet, the functionality of the endogenous TCR in CART cells has not been fully assessed. Here, we demonstrate that CART cells progressively upregulate Fas, FasL, DR5 and TRAIL, which result in their programmed cell death, independently of antigen-mediated TCR or CAR activation. CART cell apoptosis occurs even when the CAR contains a single (co-)activatory domain such as CD3ζ, CD28 or 4-1BB. Importantly, the dominant role of the Fas and DR5 pathways in CART cell apoptosis is demonstrated by the significant rescue of CART cells upon in vivo blockade by combined Fas-Fc and DR5-Fc recombinant proteins. These observations are of crucial importance for the long-term persistence of CART cells and for the development of new applications including the combined TCR and CAR activation against solid tumors

Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations.

Enteropathy-associated T-cell lymphoma (EATL), a rare and aggressive intestinal malignancy of intraepithelial T lymphocytes, comprises two disease variants (EATL-I and EATL-II) differing in clinical characteristics and pathological features. Here we report findings derived from whole-exome sequencing of 15 EATL-II tumour-normal tissue pairs. The tumour suppressor gene SETD2 encoding a non-redundant H3K36-specific trimethyltransferase is altered in 14/15 cases (93%), mainly by loss-of-function mutations and/or loss of the corresponding locus (3p21.31). These alterations consistently correlate with defective H3K36 trimethylation. The JAK/STAT pathway comprises recurrent STAT5B (60%), JAK3 (46%) and SH2B3 (20%) mutations, including a STAT5B V712E activating variant. In addition, frequent mutations in TP53, BRAF and KRAS are observed. Conversely, in EATL-I, no SETD2, STAT5B or JAK3 mutations are found, and H3K36 trimethylation is preserved. This study describes SETD2 inactivation as EATL-II molecular hallmark, supports EATL-I and -II being two distinct entities, and defines potential new targets for therapeutic intervention