Parameter identifiability of discrete Bayesian networks with hidden variables

Identifiability of parameters is an essential property for a statistical model to be useful in most settings. However, establishing parameter identifiability for Bayesian networks with hidden variables remains challenging. In the context of finite state spaces, we give algebraic arguments establishing identifiability of some special models on small DAGs. We also establish that, for fixed state spaces, generic identifiability of parameters depends only on the Markov equivalence class of the DAG. To illustrate the use of these results, we investigate identifiability for all binary Bayesian networks with up to five variables, one of which is hidden and parental to all observable ones. Surprisingly, some of these models have parameterizations that are generically 4-to-one, and not 2-to-one as label swapping of the hidden states would suggest. This leads to interesting difficulties in interpreting causal effects.Comment: 23 page

Reverse Khas'minskii condition

The aim of this paper is to present and discuss some equivalent characterizations of p-parabolicity in terms of existence of special exhaustion functions. In particular, Khas'minskii in [K] proved that if there exists a 2-superharmonic function k defined outside a compact set such that $\lim_{x\to \infty} k(x)=\infty$, then R is 2-parabolic, and Sario and Nakai in [SN] were able to improve this result by showing that R is 2-parabolic if and only if there exists an Evans potential, i.e. a 2-harmonic function $E:R\setminus K \to \R^+$ with \lim_{x\to \infty} \E(x)=\infty. In this paper, we will prove a reverse Khas'minskii condition valid for any p>1 and discuss the existence of Evans potentials in the nonlinear case.Comment: final version of the article available at http://www.springer.co

What is the impact on health and wellbeing of interventions that foster respect and social inclusion in community-residing older adults? A systematic review of quantitative and qualitative studies

Abstract Background Many interventions have been developed to promote respect and social inclusion among older people, but the evidence on their impacts on health has not been synthesised. This systematic review aims to appraise the state of the evidence across the quantitative and qualitative literature. Methods Eligible studies published between 1990 and 2015 were identified by scanning seven bibliographic databases using a pre-piloted strategy, searching grey literature and contacting experts. Studies were included if they assessed the impact (quantitatively) and/or perceived impact (qualitatively) of an intervention promoting respect and social inclusion on the physical or mental health of community-residing people aged 60 years and older. Titles and abstracts were screened for eligibility by one reviewer. A second reviewer independently screened a 10% random sample. Full texts were screened for eligibility by one reviewer, with verification by another reviewer. Risk of bias was assessed using standardised tools. Findings were summarised using narrative synthesis, harvest plots and logic models to depict the potential pathways to health outcomes. Results Of the 27,354 records retrieved, 40 studies (23 quantitative, 6 qualitative, 11 mixed methods) were included. All studies were conducted in high and upper middle-income countries. Interventions involved mentoring, intergenerational and multi-activity programmes, dancing, music and singing, art and culture and information-communication technology. Most studies (n = 24) were at high or moderate risk of bias. Music and singing, intergenerational interventions, art and culture and multi-activity interventions were associated with an overall positive impact on health outcomes. This included depression (n = 3), wellbeing (n = 3), subjective health (n = 2), quality of life (n = 2), perceived stress and mental health (n = 2) and physical health (n = 2). Qualitative studies offered explanations for mediating factors (e.g. improved self-esteem) that may lead to improved health outcomes and contributed to the assessment of causation. Conclusions Whilst this review suggests that some interventions may positively impact on the health outcomes of older people, and identified mediating factors to health outcomes, the evidence is based on studies with heterogeneous methodologies. Many of the interventions were delivered as projects to selected groups, raising important questions about the feasibility of wider implementation and the potential for population-wide benefits. Systematic review registration PROSPERO registration number CRD4201401010

Validation of an Engineered Cell Model for In Vitro and In Vivo HIF-1 alpha Evaluation by Different Imaging Modalities

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[18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of 3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients

A Practical Method to Test the Safety of HV/MV Substation Grounding System

The adequacy of a Grounding System (GS) to the safety conditions has to be periodically tested by measurements. The test methods and techniques used to verify the electrical characteristics of the GS include the measurements of step and touch voltages. The goal of the test is to verify that touch voltage and step voltage remain below a safe value in all the zones of the installation. The measurements can present some operational difficulties. The purpose of this paper is to present the procedure, step-by-step, of a practical method of measuring touch/step voltages in grounding systems located in urban or industrial areas with reduced accessibility. The suggested method uses auxiliary current electrodes located at short distances. This paper demonstrates by test measurements done in a real case that the method provides conservative results

Combined low densities of FoxP3+ and CD3+ tumor-infiltrating lymphocytes identify stage II colorectal cancer at high risk of progression

The densities of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs), combined with TNM (tumor-node-metastasis) staging, have prognostic value for nonmetastatic colorectal cancer (CRC) patients. We compared the prognostic value of CD3+ and FoxP3+ TILs at the invasive front, TNM classifiers, and microsatellite (MS) status in a trial set of patients with stage II-III CRC (n = 413), by recursive partitioning with a classification and regression tree (CART). Significant prognostic factors and interactions were re-assessed by logistic regression and Cox proportional-hazards modeling in the trial and a validation set (n = 215) of patients with stage II CRC. In the trial set, CART indicated that TIL numbers were of value only in predicting recurrence risk for stage II cancers, where low densities of FoxP3+ TILs ranked first and low densities of CD3+ TILs further stratifiying risk. Multivariate analysis showed that TILs interacted with tumor stage (FoxP3+, P = 0.06; CD3+, P = 0.02) and MS instability (FoxP3+; P = 0.02). In stage II MS-stable cancers, concomitant low densities of both FoxP3+ and CD3+ TILs identified patients with the highest progression risk in the trial (HR 7.24; 95%CI, 3.41-15.4; P < 0.001) and the validation (HR 15.16; 95% IC, 3.43-66.9; P < 0.001) sets. FoxP3+ and CD3+ TIL load in CRC was more informative than other prognostic factors before the cancer progressed to lymph nodes. This prognostic information about TILs, including FoxP3+ cells, suggests that randomized controlled trials might be refined to include interactions between TNM status, molecular classifiers, and post-surgical treatments

Identification and characterization of a novel SCYL3-NTRK1 rearrangement in a colorectal cancer patient

In colorectal cancer patients, chromosomal rearrangements involving NTRK1 gene (encoding the TRKA protein) are shown in a small subset of patients and are associated with the constitutive activation of the kinase domain of TRKA. In turn, activated TRKA-fusion proteins are associated with proliferation and survival in colorectal cancer tumors. Here we report the identification and functional characterization of a new SCYL3-NTRK1 fusion gene in a 61-year-old colorectal cancer patient. To our knowledge, this fusion protein has never been previously documented in oncological patients. We show that this novel fusion is oncogenic and sensitive to TRKA inhibitors. As suggested by other pieces of evidence, entrectinib - an orally available pan- TRK, ROS1 and ALK inhibitor - may have particular efficacy in patients with NTRK rearrangements. Therefore, screening for rearrangements involving NTRK genes may help identifying a subset of patients able to derive benefit from treatment with entrectinib or other targeted inhibitors