A Comparison of Multi-instance Learning Algorithms

Motivated by various challenging real-world applications, such as drug activity prediction and image retrieval, multi-instance (MI) learning has attracted considerable interest in recent years. Compared with standard supervised learning, the MI learning task is more difficult as the label information of each training example is incomplete. Many MI algorithms have been proposed. Some of them are specifically designed for MI problems whereas others have been upgraded or adapted from standard single-instance learning algorithms. Most algorithms have been evaluated on only one or two benchmark datasets, and there is a lack of systematic comparisons of MI learning algorithms. This thesis presents a comprehensive study of MI learning algorithms that aims to compare their performance and find a suitable way to properly address different MI problems. First, it briefly reviews the history of research on MI learning. Then it discusses five general classes of MI approaches that cover a total of 16 MI algorithms. After that, it presents empirical results for these algorithms that were obtained from 15 datasets which involve five different real-world application domains. Finally, some conclusions are drawn from these results: (1) applying suitable standard single-instance learners to MI problems can often generate the best result on the datasets that were tested, (2) algorithms exploiting the standard asymmetric MI assumption do not show significant advantages over approaches using the so-called collective assumption, and (3) different MI approaches are suitable for different application domains, and no MI algorithm works best on all MI problems

Abdominal functional electrical stimulation to enhance mechanical insufflation-exsufflation

Context: Respiratory complications, attributed to the build-up of secretions in the airway, are a leading cause of rehospitalisation for the tetraplegic population. Previously, we observed that the application of Abdominal Functional Electrical Stimulation (AFES) improved cough function and increased demand for secretion removal, suggesting AFES may aid secretion clearance. Clinically, secretion clearance is commonly achieved by using Mechanical insufflation-exsufflation (MI-E) to simulate a cough. In this study the feasibility of combining AFES with MI-E is evaluated. Findings: AFES was successfully combined with MI-E at eight fortnightly assessment sessions conducted with one sub-acute participant with tetraplegia. By using the signal from a pressure sensor, integrated with the MI-E device, AFES was correctly applied in synchrony with MI-E with an accuracy of 96.7%. Acute increases in exhaled volume and peak flow were observed during AFES assisted MI-E, compared to MI-E alone, at six of eight assessment sessions. Conclusion: The successful integration of AFES with MI-E at eight assessment sessions demonstrates the feasibility of this technique. The acute increases in respiratory function observed at the majority of assessment sessions generate the hypothesis that AFES assisted MI-E may be more effective for secretion clearance than MI-E alone

Superfluid, Mott-Insulator, and Mass-Density-Wave Phases in the One-Dimensional Extended Bose-Hubbard Model

We use the finite-size density-matrix-renormalization-group (FSDMRG) method to obtain the phase diagram of the one-dimensional ($d = 1$) extended Bose-Hubbard model for density $\rho = 1$ in the $U-V$ plane, where $U$ and $V$ are, respectively, onsite and nearest-neighbor interactions. The phase diagram comprises three phases: Superfluid (SF), Mott Insulator (MI) and Mass Density Wave (MDW). For small values of $U$ and $V$, we get a reentrant SF-MI-SF phase transition. For intermediate values of interactions the SF phase is sandwiched between MI and MDW phases with continuous SF-MI and SF-MDW transitions. We show, by a detailed finite-size scaling analysis, that the MI-SF transition is of Kosterlitz-Thouless (KT) type whereas the MDW-SF transition has both KT and two-dimensional-Ising characters. For large values of $U$ and $V$ we get a direct, first-order, MI-MDW transition. The MI-SF, MDW-SF and MI-MDW phase boundaries join at a bicritical point at ($U, V) = (8.5 \pm 0.05, 4.75 \pm 0.05)$.Comment: 10 pages, 15 figure

Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (R(i)) from 19 to 7 h and improved organ dysfunction with enhanced alveolar–capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (R(i); 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation

Motivational Interviewing for Parent-child Health Interventions: A Systematic Review and Meta-Analysis

Purpose: Motivational interviewing (MI) is a patient-centered approach focusing on building intrinsic motivation for change. This paper presents a meta-analysis of parent-involved MI to improve pediatric health behavior and health outcomes. Methods: Study inclusion criteria: (1) examined modifiable pediatric health behaviors (\u3c 18 years old); (2) used MI or motivational enhancement; (3) conducted a randomized controlled trial with a comparison group (non-MI control or active treatment group); (4) conducted the intervention with only a parent or both a parent and child; and (5) were written in English. Twenty-five studies (with 5,130 participants) were included and independently rated. Weighted mean effect sizes, using random-effects assumptions, were calculated. Results: Relative to comparison groups, MI was associated with significant improvements in health behaviors (e.g., oral health, diet, physical activity, reduced screen time, smoking cessation, reduced second hand smoke) and reduction in body mass index. Results suggest that MI may also outperform comparison groups in terms of dental caries, but more studies are needed. MI interventions were more successful at improving diets for Caucasians and when the intervention included more MI components. Conclusions: Our findings provide support for providing motivational interviewing to parents and children to improve pediatric health behaviors

Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure

Aims: Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. Methods and results: Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca2+ handling with more spontaneous Ca2+ release events, increased diastolic Ca2+, lower Ca2+ amplitude, and prolonged time to diastolic Ca2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (−35%, P < 0.01) and sarcoplasmic reticulum Ca2+ adenosine triphosphatase 2a (SERCA2a) function (−26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. Conclusions: Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF