Showing papers by "Temple University published in 2013"

Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia

Abstract: BACKGROUND—Many mutations that contribute to the pathogenesis of acute myeloid leukemia (AML) are undefined The relationships between patterns of mutations and epigenetic phenotypes are not yet clear METHODS—We analyzed the genomes of 200 clinically annotated adult cases of de novo AML, using either whole-genome sequencing (50 cases) or whole-exome sequencing (150 cases), along with RNA and microRNA sequencing and DNA-methylation analysis RESULTS—AML genomes have fewer mutations than most other adult cancers, with an average of only 13 mutations found in genes Of these, an average of 5 are in genes that are recurrently mutated in AML A total of 23 genes were significantly mutated, and another 237 were mutated in two or more samples Nearly all samples had at least 1 nonsynonymous mutation in one of nine categories of genes that are almost certainly relevant for pathogenesis, including transcriptionfactor fusions (18% of cases), the gene encoding nucleophosmin (NPM1) (27%), tumorsuppressor genes (16%), DNA-methylation–related genes (44%), signaling genes (59%), chromatin-modifying genes (30%), myeloid transcription-factor genes (22%), cohesin-complex genes (13%), and spliceosome-complex genes (14%) Patterns of cooperation and mutual exclusivity suggested strong biologic relationships among several of the genes and categories CONCLUSIONS—We identified at least one potential driver mutation in nearly all AML samples and found that a complex interplay of genetic events contributes to AML pathogenesis in individual patients The databases from this study are widely available to serve as a foundation for further investigations of AML pathogenesis, classification, and risk stratification (Funded by the National Institutes of Health) The molecular pathogenesis of acute myeloid leukemia (AML) has been studied with the use of cytogenetic analysis for more than three decades Recurrent chromosomal structural variations are well established as diagnostic and prognostic markers, suggesting that acquired genetic abnormalities (ie, somatic mutations) have an essential role in pathogenesis 1,2 However, nearly 50% of AML samples have a normal karyotype, and many of these genomes lack structural abnormalities, even when assessed with high-density comparative genomic hybridization or single-nucleotide polymorphism (SNP) arrays 3-5 (see Glossary) Targeted sequencing has identified recurrent mutations in FLT3, NPM1, KIT, CEBPA, and TET2 6-8 Massively parallel sequencing enabled the discovery of recurrent mutations in DNMT3A 9,10 and IDH1 11 Recent studies have shown that many patients with

Digital business strategy: toward a next generation of insights

Abstract: Over the last three decades, the prevailing view of information technology strategy has been that it is a functional-level strategy that must be aligned with the firm's chosen business strategy. Even within this so-called alignment view, business strategy directed IT strategy. During the last decade, the business infrastructure has become digital with increased interconnections among products, processes, and services. Across many firms spanning different industries and sectors, digital technologies (viewed as combinations of information, computing, communication, and connectivity technologies) are fundamentally transforming business strategies, business processes, firm capabilities, products and services, and key interfirm relationships in extended business networks. Accordingly, we argue that the time is right to rethink the role of IT strategy, from that of a functional-level strategy--aligned but essentially always subordinate to business strategy--to one that reflects a fusion between IT strategy and business strategy. This fusion is herein termed digital business strategy. We identify four key themes to guide our thinking on digital business strategy and help provide a framework to define the next generation of insights. The four themes are (1) the scope of digital business strategy, (2) the scale of digital business strategy, (3) the speed of digital business strategy, and (4) the sources of business value creation and capture in digital business strategy. After elaborating on each of these four themes, we discuss the success metrics and potential performance implications from pursuing a digital business strategy. We also show how the papers in the special issue shed light on digital strategies and offer directions to advance insights and shape future research.

The malleability of spatial skills: a meta-analysis of training studies.

Abstract: spatial skills. After eliminating outliers, the average effect size (Hedges’s g) for training relative to control was 0.47 (SE 0.04). Training effects were stable and were not affected by delays between training and posttesting. Training also transferred to other spatial tasks that were not directly trained. We analyzed the effects of several moderators, including the presence and type of control groups, sex, age, and type of training. Additionally, we included a theoretically motivated typology of spatial skills that emphasizes 2 dimensions: intrinsic versus extrinsic and static versus dynamic (Newcombe & Shipley, in press). Finally, we consider the potential educational and policy implications of directly training spatial skills. Considered together, the results suggest that spatially enriched education could pay substantial dividends in increasing participation in mathematics, science, and engineering.

A large-scale evaluation of computational protein function prediction

Abstract: Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.

Multi-Atlas Segmentation with Joint Label Fusion

Abstract: Multi-atlas segmentation is an effective approach for automatically labeling objects of interest in biomedical images. In this approach, multiple expert-segmented example images, called atlases, are registered to a target image, and deformed atlas segmentations are combined using label fusion. Among the proposed label fusion strategies, weighted voting with spatially varying weight distributions derived from atlas-target intensity similarity have been particularly successful. However, one limitation of these strategies is that the weights are computed independently for each atlas, without taking into account the fact that different atlases may produce similar label errors. To address this limitation, we propose a new solution for the label fusion problem in which weighted voting is formulated in terms of minimizing the total expectation of labeling error and in which pairwise dependency between atlases is explicitly modeled as the joint probability of two atlases making a segmentation error at a voxel. This probability is approximated using intensity similarity between a pair of atlases and the target image in the neighborhood of each voxel. We validate our method in two medical image segmentation problems: hippocampus segmentation and hippocampus subfield segmentation in magnetic resonance (MR) images. For both problems, we show consistent and significant improvement over label fusion strategies that assign atlas weights independently.

Using collective variables to drive molecular dynamics simulations

Abstract: A software framework is introduced that facilitates the application of biasing algorithms to collective variables of the type commonly employed to drive massively parallel molecular dynamics (MD) simulations. The modular framework that is presented enables one to combine existing collective variables into new ones, and combine any chosen collective variable with available biasing methods. The latter include the classic time-dependent biases referred to as steered MD and targeted MD, the temperature-accelerated MD algorithm, as well as the adaptive free-energy biases called metadynamics and adaptive biasing force. The present modular software is extensible, and portable between commonly used MD simulation engines.

Pathogenic mechanisms in HBV- and HCV-associated hepatocellular carcinoma

Abstract: Hepatocellular carcinoma (HCC) is a highly lethal cancer, with increasing worldwide incidence, that is mainly associated with chronic hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections. There are few effective treatments partly because the cell- and molecular-based mechanisms that contribute to the pathogenesis of this tumour type are poorly understood. This Review outlines pathogenic mechanisms that seem to be common to both viruses and which suggest innovative approaches to the prevention and treatment of HCC.

Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology.

Abstract: The use of primary mammalian neurons derived from embryonic central nervous system tissue is limited by the fact that once terminally differentiated into mature neurons, the cells can no longer be propagated. Transformed neuronal-like cell lines can be used in vitro to overcome this limitation. However, several caveats exist when utilizing cells derived from malignant tumors. In this context, the popular SH-SY5Y neuroblastoma cell line and its use in in vitro systems is described. Originally derived from a metastatic bone tumor biopsy, SH-SY5Y (ATCC® CRL-2266™) cells are a subline of the parental line SK-N-SH (ATCC® HTB-11™). SK-N-SH were subcloned three times; first to SH-SY, then to SH-SY5, and finally to SH-SY5Y. SH-SY5Y were deposited to the ATCC® in 1970 by June L. Biedler. Three important characteristics of SH-SY5Y cells should be considered when using these cells in in vitro studies. First, cultures include both adherent and floating cells, both types of which are viable. Few studies address the biological significance of the adherent versus floating phenotypes, but most reported studies utilize adherent populations and discard the floating cells during media changes. Second, early studies by Biedler's group indicated that the parental differentiated SK-N-SH cells contained two morphologically distinct phenotypes: neuroblast-like cells and epithelial-like cells (Ross et al., J Natl Cancer Inst 71(4):741-747, 1983). These two phenotypes may correspond to the "N" and "S" types described in later studies in SH-SY5Y by Encinas et al. (J Neurochem 75(3):991-1003, 2000). Cells with neuroblast-like morphology are positive for tyrosine hydroxylase (TH) and dopamine-β-hydroxylase characteristic of catecholaminergic neurons, whereas the epithelial-like counterpart cells lacked these enzymatic activities (Ross et al., J Natl Cancer Inst 71(4):741-747, 1983). Third, SH-SY5Y cells can be differentiated to a more mature neuron-like phenotype that is characterized by neuronal markers. There are several methods to differentiate SH-SY5Y cells and are mentioned below. Retinoic acid is the most commonly used means for differentiation and will be addressed in detail.

Oligodendrocyte progenitors balance growth with self-repulsion to achieve homeostasis in the adult brain.

Abstract: The adult CNS contains an abundant population of oligodendrocyte precursor cells (NG2(+) cells) that generate oligodendrocytes and repair myelin, but how these ubiquitous progenitors maintain their density is unknown. We generated NG2-mEGFP mice and used in vivo two-photon imaging to study their dynamics in the adult brain. Time-lapse imaging revealed that NG2(+) cells in the cortex were highly dynamic; they surveyed their local environment with motile filopodia, extended growth cones and continuously migrated. They maintained unique territories though self-avoidance, and NG2(+) cell loss though death, differentiation or ablation triggered rapid migration and proliferation of adjacent cells to restore their density. NG2(+) cells recruited to sites of focal CNS injury were similarly replaced by a proliferative burst surrounding the injury site. Thus, homeostatic control of NG2(+) cell density through a balance of active growth and self-repulsion ensures that these progenitors are available to replace oligodendrocytes and participate in tissue repair.

Dissecting the uncinate fasciculus: disorders, controversies and a hypothesis.

Abstract: The uncinate fasciculus is a bidirectional, long-range white matter tract that connects lateral orbitofrontal cortex and Brodmann area 10 with the anterior temporal lobes. Although abnormalities in the uncinate fasciculus have been associated with several psychiatric disorders and previous studies suggest it plays a putative role in episodic memory, language and social emotional processing, its exact function is not well understood. In this review we summarize what is currently known about the anatomy of the uncinate, we review its role in psychiatric and neurological illnesses, and we evaluate evidence related to its putative functions. We propose that an overarching role of the uncinate fasciculus is to allow temporal lobe-based mnemonic associations (e.g. an individual’s name + face + voice) to modify behaviour through interactions with the lateral orbitofrontal cortex, which provides valence-based biasing of decisions. The bidirectionality of the uncinate fasciculus information flow allows orbital frontal cortex-based reward and punishment history to rapidly modulate temporal lobe-based mnemonic representations. According to this view, disruption of the uncinate may cause problems in the expression of memory to guide decisions and in the acquisition of certain types of learning and memory. Moreover, uncinate perturbation should cause problems that extend beyond memory to include social–emotional problems owing to people and objects being stripped of personal value and emotional history and lacking in higher-level motivational value.

Targeting mitochondrial reactive oxygen species as novel therapy for inflammatory diseases and cancers

Abstract: There are multiple sources of reactive oxygen species (ROS) in the cell. As a major site of ROS production, mitochondria have drawn considerable interest because it was recently discovered that mitochondrial ROS (mtROS) directly stimulate the production of proinflammatory cytokines and pathological conditions as diverse as malignancies, autoimmune diseases, and cardiovascular diseases all share common phenotype of increased mtROS production above basal levels. Several excellent reviews on this topic have been published, but ever-changing new discoveries mandated a more up-to-date and comprehensive review on this topic. Therefore, we update recent understanding of how mitochondria generate and regulate the production of mtROS and the function of mtROS both in physiological and pathological conditions. In addition, we describe newly developed methods to probe or scavenge mtROS and compare these methods in detail. Thorough understanding of this topic and the application of mtROS-targeting drugs in the research is significant towards development of better therapies to combat inflammatory diseases and inflammatory malignancies.

An Empirical Examination of the Antecedents and Consequences of Contribution Patterns in Crowd-Funded Markets

Abstract: Crowd-funded markets have recently emerged as a novel source of capital for entrepreneurs. As the economic potential of these markets is now being realized, they are beginning to go mainstream, a trend reflected by the explicit attention crowdfunding has received in the American Jobs Act as a potential avenue for economic growth, as well as the recent focus that regulators such as the U.S. Securities and Exchange Commission have placed upon it. Although the formulation of regulation and policy surrounding crowd-funded markets is becoming increasingly important, the behavior of crowdfunders, an important aspect that must be considered in this formulation effort, is not yet well understood. A key factor that can influence the behavior of crowd funders is information on prior contribution behavior, including the amount and timing of others’ contributions, which is published for general consumption. With that in mind, in this study, we empirically examine social influence in a crowd-funded marketplace for online journalism projects, employing a unique data set that incorporates contribution events and Web traffic statistics for approximately 100 story pitches. This data set allows us to examine both the antecedents and consequences of the contribution process. First, noting that digital journalism is a form of public good, we evaluate the applicability of two competing classes of economic models that explain private contribution toward public goods in the presence of social information: substitution models and reinforcement models. We also propose a new measure that captures both the amount and the timing of others’ contribution behavior: contribution frequency (dollars per unit time). We find evidence in support of a substitution model, which suggests a partial crowding-out effect, where contributors may experience a decrease in their marginal utility from making a contribution as it becomes less important to the recipient. Further, we find that the duration of funding and, more importantly, the degree of exposure that a pitch receives over the course of the funding process, are positively associated with readership upon the story’s publication. This appears to validate the widely held belief that a key benefit of the crowdfunding model is the potential it offers for awareness and attention-building around causes and ventures. This last aspect is a major contribution of the study, as it demonstrates a clear linkage between marketing effort and the success of crowd-funded projects.

MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study

Abstract: Summary Background Patients with melanoma harbouring Val600 BRAF mutations benefit from treatment with BRAF inhibitors. However, no targeted treatments exist for patients with BRAF wild-type tumours, including those with NRAS mutations. We aimed to assess the use of MEK162, a small-molecule MEK1/2 inhibitor, in patients with NRAS -mutated or Val600 BRAF -mutated advanced melanoma. Methods In our open-label, non-randomised, phase 2 study, we assigned patients with NRAS -mutated or BRAF -mutated advanced melanoma to one of three treatment arms on the basis of mutation status. Patients were enrolled at university hospitals or private cancer centres in Europe and the USA. The three arms were: twice-daily MEK162 45 mg for NRAS -mutated melanoma, twice-daily MEK162 45 mg for BRAF -mutated melanoma, and twice-daily MEK162 60 mg for BRAF -mutated melanoma. Previous treatment with BRAF inhibitors was permitted, but previous MEK inhibitor therapy was not allowed. The primary endpoint was the proportion of patients who had an objective response (ie, a complete response or confirmed partial response). We report data for the 45 mg groups. We assessed clinical activity in all patients who received at least one dose of MEK162 and in patients assessable for response (with two available CT scans). This study is registered with ClinicalTrials.gov, number NCT01320085, and is currently recruiting additional patients with NRAS mutations (based on a protocol amendment). Findings Between March 31, 2011, and Jan 17, 2012, we enrolled 71 patients who received at least one dose of MEK162 45 mg. By Feb 29, 2012 (data cutoff), median follow-up was 3·3 months (range 0·6–8·7; IQR 2·2–5·0). No patients had a complete response. Six (20%) of 30 patients with NRAS -mutated melanoma had a partial response (three confirmed) as did eight (20%) of 41 patients with BRAF -mutated melanoma (two confirmed). The most frequent adverse events were acneiform dermatitis (18 [60%] patients with NRAS -mutated melanoma and 15 [37%] patients with the BRAF -mutated melanoma), rash (six [20%] and 16 [39%]), peripheral oedema (ten [33%] and 14 [34%]), facial oedema (nine [30%] and seven [17%]), diarrhoea (eight [27%] and 15 [37%]), and creatine phosphokinase increases (11 [37%] and nine [22%]). Increased creatine phosphokinase was the most common grade 3–4 adverse event (seven [23%] and seven [17%]). Four patients had serious adverse events (two per arm), which included diarrhoea, dehydration, acneiform dermatitis, general physical deterioration, irregular heart rate, malaise, and small intestinal perforation. No deaths occurred from treatment-related causes. Interpretation To our knowledge, MEK162 is the first targeted therapy to show activity in patients with NRAS -mutated melanoma and might offer a new option for a cancer with few effective treatments. Funding Novartis Pharmaceuticals.

Co-opted Boards

Abstract: We argue that not all independent directors are equally effective in monitoring top management. Specifically, directors who are appointed by the CEO are likely to have stronger allegiance to the CEO and will be weaker monitors. To examine this hypothesis, we propose and empirically deploy two new measures of board composition. Co-option is the fraction of the board comprised of directors appointed after the sitting CEO assumed office. Consistent with Co-option serving to measure board capture, as Co-option increases board monitoring intensity decreases: turnover-performance sensitivity diminishes; pay level increases but without a commensurate increase in pay-performance sensitivity; and investment in hard assets increases. Further analysis suggests that even independent directors who are co-opted are less effective monitors. Non-Co-opted Independence –– the fraction of the board comprised of independent directors who were already on the board before the CEO assumed office –– has more explanatory power for monitoring effectiveness than the traditional measure of board independence.

Adrenergic nervous system in heart failure: pathophysiology and therapy.

Abstract: Heart failure (HF), the leading cause of death in the western world, develops when a cardiac injury or insult impairs the ability of the heart to pump blood and maintain tissue perfusion. It is characterized by a complex interplay of several neurohormonal mechanisms that become activated in the syndrome to try and sustain cardiac output in the face of decompensating function. Perhaps the most prominent among these neurohormonal mechanisms is the adrenergic (or sympathetic) nervous system (ANS), whose activity and outflow are enormously elevated in HF. Acutely, and if the heart works properly, this activation of the ANS will promptly restore cardiac function. However, if the cardiac insult persists over time, chances are the ANS will not be able to maintain cardiac function, the heart will progress into a state of chronic decompensated HF, and the hyperactive ANS will continue to push the heart to work at a level much higher than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes a major problem in HF, conferring significant toxicity to the failing heart and markedly increasing its morbidity and mortality. The present review discusses the role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms of regulation of ANS activity and how they go awry in chronic HF, methods of measuring ANS activity in HF, the molecular alterations in heart physiology that occur in HF, along with their pharmacological and therapeutic implications, and, finally, drugs and other therapeutic modalities used in HF treatment that target or affect the ANS and its effects on the failing heart.

Integrative Genomic Characterization of Oral Squamous Cell Carcinoma Identifies Frequent Somatic Drivers

Abstract: The survival of patients with oral squamous cell carcinoma (OSCC) has not changed significantly in several decades, leading clinicians and investigators to search for promising molecular targets. To this end, we performed comprehensive genomic analysis of gene expression, copy number, methylation and point mutations in OSCC. Integrated analysis revealed more somatic events than previously reported, identifying four major driver pathways (mitogenic signaling, Notch, cell cycle, TP53) and two additional key genes (FAT1, CASP8). The Notch pathway was defective in 66% of patients, and in follow-up studies of mechanism, functional NOTCH1 signaling inhibited proliferation of OSCC cell lines. Frequent mutation of CASP8 defines a new molecular subtype of OSCC with few copy number changes. Although genomic alterations are dominated by loss of tumor suppressor genes, 80% of patients harbored at least one genomic alteration in a targetable gene, suggesting that novel approaches to treatment may be possible for this debilitating disease.

Social Media and Firm Equity Value

Abstract: Companies have increasingly advocated social media technologies to transform businesses and improve organizational performance. This study scrutinizes the predictive relationships between social media and firm equity value, the relative effects of social media metrics compared with conventional online behavioral metrics, and the dynamics of these relationships. The results derived from vector autoregressive models suggest that social media-based metrics (web blogs and consumer ratings) are significant leading indicators of firm equity value. Interestingly, conventional online behavioral metrics (Google searches and web traffic) are found to have a significant yet substantially weaker predictive relationship with firm equity value than social media metrics. We also find that social media has a faster predictive value, i.e., shorter “wear-in” time, than conventional online media. These findings are robust to a consistent set of volume-based measures (total blog posts, rating volume, total page views, and search intensity). Collectively, this study proffers new insights for senior executives with respect to firm equity valuations and the transformative power of social media.

The Teenage Brain: Peer Influences on Adolescent Decision Making

Abstract: Research efforts to account for elevated risk behavior among adolescents have arrived at an exciting new stage. Moving beyond laboratory studies of age differences in "cool" cognitive processes related to risk perception and reasoning, new approaches have shifted focus to the influence of social and emotional factors on adolescent neurocognition. We review recent research suggesting that adolescent risk-taking propensity derives in part from a maturational gap between early adolescent remodeling of the brain's socio-emotional reward system and a gradual, prolonged strengthening of the cognitive control system. At a time when adolescents spend an increasing amount of time with their peers, research suggests that peer-related stimuli may sensitize the reward system to respond to the reward value of risky behavior. As the cognitive control system gradually matures over the course of the teenage years, adolescents grow in their capacity to coordinate affect and cognition, and to exercise self-regulation even in emotionally arousing situations. These capacities are reflected in gradual growth in the capacity to resist peer influence.

MCUR1 is an essential component of mitochondrial Ca2+ uptake that regulates cellular metabolism

Abstract: Ca(2+) flux across the mitochondrial inner membrane regulates bioenergetics, cytoplasmic Ca(2+) signals and activation of cell death pathways. Mitochondrial Ca(2+) uptake occurs at regions of close apposition with intracellular Ca(2+) release sites, driven by the inner membrane voltage generated by oxidative phosphorylation and mediated by a Ca(2+) selective ion channel (MiCa; ref. ) called the uniporter whose complete molecular identity remains unknown. Mitochondrial calcium uniporter (MCU) was recently identified as the likely ion-conducting pore. In addition, MICU1 was identified as a mitochondrial regulator of uniporter-mediated Ca(2+) uptake in HeLa cells. Here we identified CCDC90A, hereafter referred to as MCUR1 (mitochondrial calcium uniporter regulator 1), an integral membrane protein required for MCU-dependent mitochondrial Ca(2+) uptake. MCUR1 binds to MCU and regulates ruthenium-red-sensitive MCU-dependent Ca(2+) uptake. MCUR1 knockdown does not alter MCU localization, but abrogates Ca(2+) uptake by energized mitochondria in intact and permeabilized cells. Ablation of MCUR1 disrupts oxidative phosphorylation, lowers cellular ATP and activates AMP kinase-dependent pro-survival autophagy. Thus, MCUR1 is a critical component of a mitochondrial uniporter channel complex required for mitochondrial Ca(2+) uptake and maintenance of normal cellular bioenergetics.

Using Facebook and text messaging to deliver a weight loss program to college students.

Abstract: Objective: Between 31 and 35% of the college-aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and initial efficacy of a technology-based 8-week weight loss intervention among college students. Design and Methods: Students (N = 52) were randomly assigned to one of the three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List control (n = 17), with assessments at 4 weeks and 8 weeks (post-treatment). Participants were 20.47 ± 2.19 years old, 86.45 ± 17.11 kg, with a body mass index of 31.36 ± 5.3 kg/m2. Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, and 5.7% other races). Results: The primary outcome was weight loss after 8 weeks (post-treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (−2.4 ± 2.5 kg) than the Facebook (−0.63 ± 2.4 kg) and Waiting List (−0.24 ± 2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups. Conclusions: Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.

Music for stress and anxiety reduction in coronary heart disease patients

Abstract: Background Individuals with coronary heart disease (CHD) often suffer from severe distress due to diagnosis, hospitalization, surgical procedures, uncertainty of outcome, fear of dying, doubts about progress in recovery, helplessness and loss of control. Such adverse effects put the cardiac patient at greater risk for complications, including sudden cardiac death. It is therefore of crucial importance that the care of people with CHD focuses on psychological as well as physiological needs. Music interventions have been used to reduce anxiety and distress and improve physiological functioning in medical patients; however its efficacy for people with CHD needs to be evaluated. Objectives To update the previously published review that examined the effects of music interventions with standard care versus standard care alone on psychological and physiological responses in persons with CHD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 10), MEDLINE (OvidSP, 1950 to October week 4 2012), EMBASE (OvidSP, 1974 to October week 5 2012), CINAHL (EBSCOhost, 1982 to 9 November 2012), PsycINFO (OvidSP, 1806 to October week 5 2012), LILACS (Virtual Health Library, 1982 to 15 November 2012), Social Science Citation Index (ISI, 1974 to 9 November 2012), a number of other databases, and clinical trial registers. We also conducted handsearching of journals and reference lists. We applied no language restrictions. Selection criteria We included all randomized controlled trials and quasi-randomized trials that compared music interventions and standard care with standard care alone for persons with confirmed CHD. Data collection and analysis Two review authors independently extracted data and assessed methodological quality, seeking additional information from the trial researchers when necessary. We present results using weighted mean differences for outcomes measured by the same scale, and standardized mean differences for outcomes measured by different scales. We used post-intervention scores. In cases of significant baseline difference, we used change scores (changes from baseline). Main results We identified four new trials for this update. In total, the evidence for this review rests on 26 trials (1369 participants). Listening to music was the main intervention used, and 23 of the studies did not include a trained music therapist. Results indicate that music interventions have a small beneficial effect on psychological distress in people with CHD and this effect is consistent across studies (MD = -1.26, 95% CI -2.30 to -0.22, P = 0.02, I² = 0%). Listening to music has a moderate effect on anxiety in people with CHD; however results were inconsistent across studies (SMD = -0.70, 95% CI -1.17 to -0.22, P = 0.004, I² = 77%). Studies that used music interventions in people with myocardial infarction found more consistent anxiety-reducing effects of music, with an average anxiety reduction of 5.87 units on a 20 to 80 point score range (95% CI -7.99 to -3.75, P < 0.00001, I² = 53%). Furthermore, studies that used patient-selected music resulted in greater anxiety-reducing effects that were consistent across studies (SMD = -0.89, 95% CI -1.42 to -0.36, P = 0.001, I² = 48%). Findings indicate that listening to music reduces heart rate (MD = -3.40, 95% CI -6.12 to -0.69, P = 0.01), respiratory rate (MD = -2.50, 95% CI -3.61 to -1.39, P < 0.00001) and systolic blood pressure (MD = -5.52 mmHg, 95% CI - 7.43 to -3.60, P < 0.00001). Studies that included two or more music sessions led to a small and consistent pain-reducing effect (SMD = -0.27, 95% CI -0.55 to -0.00, P = 0.05). The results also suggest that listening to music may improve patients' quality of sleep following a cardiac procedure or surgery (SMD = 0.91, 95% CI 0.03 to 1.79, P = 0.04). We found no strong evidence for heart rate variability and depression. Only one study considered hormone levels and quality of life as an outcome variable. A small number of studies pointed to a possible beneficial effect of music on opioid intake after cardiac procedures or surgery, but more research is needed to strengthen this evidence. Authors' conclusions This systematic review indicates that listening to music may have a beneficial effect on anxiety in persons with CHD, especially those with a myocardial infarction. Anxiety-reducing effects appear to be greatest when people are given a choice of which music to listen to. Furthermore, listening to music may have a beneficial effect on systolic blood pressure, heart rate, respiratory rate, quality of sleep and pain in persons with CHD. However, the clinical significance of these findings is unclear. Since many of the studies are at high risk of bias, these findings need to be interpreted with caution. More research is needed into the effects of music interventions offered by a trained music therapist.

Linear Discriminant Analysis

Abstract: Suppose we are given a learning set \(\mathcal{L}\) of multivariate observations (i.e., input values \(\mathfrak{R}^r\)), and suppose each observation is known to have come from one of K predefined classes having similar characteristics. These classes may be identified, for example, as species of plants, levels of credit worthiness of customers, presence or absence of a specific medical condition, different types of tumors, views on Internet censorship, or whether an e-mail message is spam or non-spam.

Salient Region Detection by UFO: Uniqueness, Focusness and Objectness

Abstract: The goal of saliency detection is to locate important pixels or regions in an image which attract humans' visual attention the most. This is a fundamental task whose output may serve as the basis for further computer vision tasks like segmentation, resizing, tracking and so forth. In this paper we propose a novel salient region detection algorithm by integrating three important visual cues namely uniqueness, focus ness and objectness (UFO). In particular, uniqueness captures the appearance-derived visual contrast, focus ness reflects the fact that salient regions are often photographed in focus, and objectness helps keep completeness of detected salient regions. While uniqueness has been used for saliency detection for long, it is new to integrate focus ness and objectness for this purpose. In fact, focus ness and objectness both provide important saliency information complementary of uniqueness. In our experiments using public benchmark datasets, we show that, even with a simple pixel level combination of the three components, the proposed approach yields significant improvement compared with previously reported methods.

Chronic Bronchitis and Chronic Obstructive Pulmonary Disease

Abstract: Chronic bronchitis (CB) is a common but variable phenomenon in chronic obstructive pulmonary disease (COPD). It has numerous clinical consequences, including an accelerated decline in lung function, greater risk of the development of airflow obstruction in smokers, a predisposition to lower respiratory tract infection, higher exacerbation frequency, and worse overall mortality. CB is caused by overproduction and hypersecretion of mucus by goblet cells, which leads to worsening airflow obstruction by luminal obstruction of small airways, epithelial remodeling, and alteration of airway surface tension predisposing to collapse. Despite its clinical sequelae, little is known about the pathophysiology of CB and goblet cell hyperplasia in COPD, and treatment options are limited. In addition, it is becoming increasingly apparent that in the classic COPD spectrum, with emphysema on one end and CB on the other, most patients lie somewhere in the middle. It is known now that many patients with severe emphysema can ...

Swift Guanxi in Online Marketplaces: The Role of Computer-Mediated Communication Technologies

Abstract: The concept of guanxi (ie, a close and pervasive interpersonal relationship) has received little attention in the literature on online marketplaces, perhaps due to their impersonal nature However, we propose that computer-mediated communication (CMC) technologies can mimic traditional interactive face-to-face communications, thus enabling a form of guanxi in online marketplaces Extending the literature on traditional guanxi, we herein introduce the concept of swift guanxi, conceptualized as the buyer’s perception of a swiftly formed interpersonal relationship with a seller, which consists of mutual understanding, reciprocal favors, and relationship harmonyIntegrating theories of CMC and guanxi, we develop a model that explains how a set of CMC tools (ie, instant messaging, message box, feedback system) facilitate repeat transactions with sellers by building swift guanxi and trust through interactivity and presence (social presence and telepresence) with sellers Longitudinal data from 338 buyers in TaoBao, China’s leading online marketplace, support our structural model, showing that the buyers’ effective use of CMC tools enable swift guanxi and trust by enhancing the buyers’ perceptions of interactivity and presence In turn, swift guanxi and trust predict buyers’ repurchase intentions and their actual repurchases from sellers We discuss the implications of swift guanxi in online marketplaces with the aid of CMC technologies

A Comparison of Treating Metabolic Acidosis in CKD Stage 4 Hypertensive Kidney Disease with Fruits and Vegetables or Sodium Bicarbonate

Abstract: Summary Background and objectives Current guidelines recommend Na + -based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) , 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury. Design, setting, participants, & measurements Individuals with stage 4 (eGFR, 15–29 ml/min per 1.73 m 2 )C KD due to hypertensive nephropathy, had a PTCO2 level , 22 mM, and were receiving angiotensin-converting enzymeinhibitionwererandomlyassignedto 1yearofdailyoralNaHCO3at1.0mEq/kgperday(n=35)orfruits and vegetables dosed to reduce dietary acid by half (n=36). ResultsPlasmacystatinC–calculatedeGFRdidnotdifferatbaselineand1yearbetweengroups.One-yearPTCO2 was higher than baseline in the HCO3 group (21.261.3 versus 19.561.5 mM; P,0.01) and the fruits and vegetables group (19.961.7 versus 19.361.9 mM; P,0.01), consistent with improved metabolic acidosis, and was higher in the HCO3 than the fruits and vegetable group (P,0.001). One-year urine indices of kidney injury were lower than baseline in both groups. Plasma [K + ] did not increase in either group. ConclusionsOneyearoffruitsandvegetablesorNaHCO3inindividualswithstage4CKDyieldedeGFRthatwas not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urineindicesofkidneyinjury.Thedataindicatethatfruitsandvegetablesimprovemetabolicacidosisandreduce kidney injury in stage 4 CKD without producing hyperkalemia.

Interventions for preventing and treating pelvic and back pain in pregnancy

Abstract: Background More than two-thirds of pregnant women experience low-back pain (LBP) and almost one-fifth experience pelvic pain. Pain increases with advancing pregnancy and interferes with work, daily activities and sleep. Objectives To assess the effects of interventions for preventing and treating pelvic and back pain in pregnancy. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (18 July 2012), identified related studies and reviews from the Cochrane Back Review Group search strategy to July 2012, and checked reference lists from identified reviews and studies. Selection criteria Randomised controlled trials (RCTs) of any treatment to prevent or reduce the incidence or severity of pelvic or back pain in pregnancy. Data collection and analysis Two review authors independently assessed risk of bias and extracted data. Quality of the evidence for outcomes was assessed using the five criteria outlined by the GRADE Working Group. Main results We included 26 randomised trials examining 4093 pregnant women in this updated review. Eleven trials examined LBP (N = 1312), four examined pelvic pain (N = 661), and 11 trials examined lumbo-pelvic (LBP and pelvic) pain (N = 2120). Diagnoses ranged from self-reported symptoms to the results of specific tests. All interventions were added to usual prenatal care and unless noted, were compared to usual prenatal care. For LBP, there was low-quality evidence that in general, the addition of exercise significantly reduced pain (standardised mean difference (SMD) -0.80; 95% confidence interval (CI) -1.07 to -0.53; six RCTs, N = 543), and disability (SMD -0.56; 95% CI -0.89 to -0.23; two RCTs, N = 146); and water-based exercise significantly reduced LBP-related sick leave (risk ratio (RR) 0.40; 95% CI 0.17 to 0.92; one RCT, N = 241). Low-quality evidence from single trials suggested no significant difference in pain or function between two types of pelvic support belt, between osteopathic manipulation (OMT) and usual care or sham ultrasound (sham US). Very low-quality evidence suggested that a specially-designed pillow may relieve night pain better than a regular pillow. For pelvic pain, there was moderate-quality evidence that acupuncture significantly reduced evening pain better than exercise; both were better than usual care. Low-quality evidence from single trials suggested that adding a rigid belt to exercise improved average pain but not function; acupuncture was significantly better than sham acupuncture for improving evening pain and function, but not average pain; and evening pain relief was the same following either deep or superficial acupuncture. For lumbo-pelvic pain, there was moderate-quality evidence that an eight- to 20-week exercise program reduced the risk of women reporting lumbo-pelvic pain (RR 0.85; 95% CI 0.73 to 1.00; four RCTs, N = 1344); but a 16- to 20-week training program was no more successful than usual care at preventing pelvic pain (one RCT, N = 257). Low-quality evidence suggested that exercise significantly reduced lumbo-pelvic-related sick leave (RR 0.76; 95% CI 0.62 to 0.94, two RCTs, N = 1062), and improved function. Low-quality evidence from single trials suggested that OMT significantly reduced pain and improved function; either a multi-modal intervention that included manual therapy, exercise and education (MOM) or usual care significantly reduced disability, but only MOM improved pain and physical function; acupuncture improved pain and function more than usual care or physiotherapy; pain and function improved more when acupuncture was started at 26- rather than 20- weeks' gestation; and auricular (ear) acupuncture significantly improved these outcomes more than sham acupuncture. When reported, adverse events were minor and transient. Authors' conclusions Moderate-quality evidence suggested that acupuncture or exercise, tailored to the stage of pregnancy, significantly reduced evening pelvic pain or lumbo-pelvic pain more than usual care alone, acupuncture was significantly more effective than exercise for reducing evening pelvic pain, and a 16- to 20-week training program was no more successful than usual prenatal care at preventing pelvic or LBP. Low-quality evidence suggested that exercise significantly reduced pain and disability from LBP. There was low-quality evidence from single trials for other outcomes because of high risk of bias and sparse data; clinical heterogeneity precluded pooling. Publication bias and selective reporting cannot be ruled out. Physiotherapy, OMT, acupuncture, a multi-modal intervention, or the addition of a rigid pelvic belt to exercise seemed to relieve pelvic or back pain more than usual care alone. Acupuncture was more effective than physiotherapy at relieving evening lumbo-pelvic pain and disability and improving pain and function when it was started at 26- rather than 20-weeks' gestation, although the effects were small. There was no significant difference in LBP and function for different support belts, exercise, neuro emotional technique or spinal manipulation (SMT), or in evening pelvic pain between deep and superficial acupuncture. Very low-quality evidence suggested a specially-designed pillow may reduce night-time LBP. Further research is very likely to have an important impact on our confidence in the estimates of effect and is likely to change the estimates. Future research would benefit from the introduction of an agreed classification system that can be used to categorise women according to presenting symptoms.