Showing papers by "Temple University published in 2016"

MEGA7: Molecular Evolutionary Genetics Analysis version 7.0 for bigger datasets

Abstract: We present the latest version of the Molecular Evolutionary Genetics Analysis (Mega) software, which contains many sophisticated methods and tools for phylogenomics and phylomedicine. In this major upgrade, Mega has been optimized for use on 64-bit computing systems for analyzing larger datasets. Researchers can now explore and analyze tens of thousands of sequences in Mega The new version also provides an advanced wizard for building timetrees and includes a new functionality to automatically predict gene duplication events in gene family trees. The 64-bit Mega is made available in two interfaces: graphical and command line. The graphical user interface (GUI) is a native Microsoft Windows application that can also be used on Mac OS X. The command line Mega is available as native applications for Windows, Linux, and Mac OS X. They are intended for use in high-throughput and scripted analysis. Both versions are available from www.megasoftware.net free of charge.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Neurobiologic Advances from the Brain Disease Model of Addiction

Abstract: This article reviews scientific advances in the prevention and treatment of substance-use disorder and related developments in public policy. In the past two decades, research has increasingly supported the view that addiction is a disease of the brain. Although the brain disease model of addiction has yielded effective preventive measures, treatment interventions, and public health policies to address substance-use disorders, the underlying concept of substance abuse as a brain disease continues to be questioned, perhaps because the aberrant, impulsive, and compulsive behaviors that are characteristic of addiction have not been clearly tied to neurobiology. Here we review recent advances in the neurobiology of addiction to clarify the link between addiction and brain function and to broaden the understanding of addiction as a brain disease. We review findings on the desensitization of reward circuits, which dampens the ability to feel pleasure and the motivation to pursue everyday activities; the increasing strength of conditioned responses and stress reactivity, which results in increased cravings for alcohol and other drugs and negative emotions when these cravings are not sated; and the weakening of the brain regions involved in executive functions such as decision making, inhibitory control, and self-regulation that leads to repeated relapse. We also review the ways in which social environments, developmental stages, and genetics are intimately linked to and influence vulnerability and recovery. We conclude that neuroscience continues to support the brain disease model of addiction. Neuroscience research in this area not only offers new opportunities for the prevention and treatment of substance addictions and related behavioral addictions (e.g., to food, sex, and gambling) but may also improve our understanding of the fundamental biologic processes involved in voluntary behavioral control. In the United States, 8 to 10% of people 12 years of age or older, or 20 to 22 million people, are addicted to alcohol or other drugs. 1 The abuse of tobacco, alcohol, and illicit drugs in the United States exacts more than $700 billion annually in costs related to crime, lost work productivity, and health care. 2-4 After centuries of efforts to reduce addiction and its related costs by punishing addictive behaviors failed to produce adequate results, recent basic and clinical research has provided clear evidence that addiction might be better considered and treated as an acquired disease of the brain (see Box 1 for definitions of substance-use disorder and addiction). Research guided by the brain disease model of addiction has led to the development of more effective methods of prevention and treatment and to more informed public health policies. Notable examples include the Mental Health Parity and Addiction Equity Act of 2008, which requires medical insurance plans to provide the same coverage for substance-use disorders and other mental illnesses that is provided for other illnesses, 5 and the proposed bipartisan Senate legislation that From the National Institute on Drug Abuse (N.D.V.) and the National Institute of Alcohol Abuse and Alcoholism (G.F.K.) — both in Bethesda, MD; and the Treatment Research Institute, Philadelphia (A.T.M.). Address reprint requests to Dr. Volkow at the National Institute on Drug Abuse, 6001 Executive Bld., Rm. 5274, Bethesda, MD 20892, or at nvolkow@ nida . nih . gov.

Electron-Ion Collider: The next QCD frontier: Understanding the glue that binds us all

Abstract: This White Paper presents the science case of an Electron-Ion Collider (EIC), focused on the structure and interactions of gluon-dominated matter, with the intent to articulate it to the broader nuclear science community. It was commissioned by the managements of Brookhaven National Laboratory (BNL) and Thomas Jefferson National Accelerator Facility (JLab) with the objective of presenting a summary of scientific opportunities and goals of the EIC as a follow-up to the 2007 NSAC Long Range plan. This document is a culmination of a community-wide effort in nuclear science following a series of workshops on EIC physics over the past decades and, in particular, the focused ten-week program on “Gluons and quark sea at high energies” at the Institute for Nuclear Theory in Fall 2010. It contains a brief description of a few golden physics measurements along with accelerator and detector concepts required to achieve them. It has been benefited profoundly from inputs by the users’ communities of BNL and JLab. This White Paper offers the promise to propel the QCD science program in the US, established with the CEBAF accelerator at JLab and the RHIC collider at BNL, to the next QCD frontier.

Road crack detection using deep convolutional neural network

Abstract: Automatic detection of pavement cracks is an important task in transportation maintenance for driving safety assurance. However, it remains a challenging task due to the intensity inhomogeneity of cracks and complexity of the background, e.g., the low contrast with surrounding pavement and possible shadows with similar intensity. Inspired by recent success on applying deep learning to computer vision and medical problems, a deep-learning based method for crack detection is proposed in this paper. A supervised deep convolutional neural network is trained to classify each image patch in the collected images. Quantitative evaluation conducted on a data set of 500 images of size 3264 χ 2448, collected by a low-cost smart phone, demonstrates that the learned deep features with the proposed deep learning framework provide superior crack detection performance when compared with features extracted with existing hand-craft methods.

The Atlantic salmon genome provides insights into rediploidization

Abstract: The whole-genome duplication 80 million years ago of the common ancestor of salmonids (salmonid-specific fourth vertebrate whole-genome duplication, Ss4R) provides unique opportunities to learn about the evolutionary fate of a duplicated vertebrate genome in 70 extant lineages. Here we present a high-quality genome assembly for Atlantic salmon (Salmo salar), and show that large genomic reorganizations, coinciding with bursts of transposon-mediated repeat expansions, were crucial for the post-Ss4R rediploidization process. Comparisons of duplicate gene expression patterns across a wide range of tissues with orthologous genes from a pre-Ss4R outgroup unexpectedly demonstrate far more instances of neofunctionalization than subfunctionalization. Surprisingly, we find that genes that were retained as duplicates after the teleost-specific whole-genome duplication 320 million years ago were not more likely to be retained after the Ss4R, and that the duplicate retention was not influenced to a great extent by the nature of the predicted protein interactions of the gene products. Finally, we demonstrate that the Atlantic salmon assembly can serve as a reference sequence for the study of other salmonids for a range of purposes.

Targeting the cancer epigenome for therapy

Abstract: Next-generation sequencing has revealed that more than 50% of human cancers harbour mutations in enzymes that are involved in chromatin organization. Tumour cells not only are activated by genetic and epigenetic alterations, but also routinely use epigenetic processes to ensure their escape from chemotherapy and host immune surveillance. Hence, a growing emphasis of recent drug discovery efforts has been on targeting the epigenome, including DNA methylation and histone modifications, with several new drugs being tested and some already approved by the US Food and Drug Administration (FDA). The future will see the increasing success of combining epigenetic drugs with other therapies. As epigenetic drugs target the epigenome as a whole, these true 'genomic medicines' lessen the need for precision approaches to individualized therapies.

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial

Abstract: Summary Background Results from phase 2 and 3 trials in patients with advanced melanoma have shown significant improvements in the proportion of patients achieving an objective response and prolonged progression-free survival with the combination of nivolumab (an anti-PD-1 antibody) plus ipilimumab (an anti-CTLA-4 antibody) compared with ipilimumab alone. We report 2-year overall survival data from a randomised controlled trial assessing this treatment in previously untreated advanced melanoma. Methods In this multicentre, double-blind, randomised, controlled, phase 2 trial (CheckMate 069) we recruited patients from 19 specialist cancer centres in two countries (France and the USA). Eligible patients were aged 18 years or older with previously untreated, unresectable stage III or IV melanoma and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned 2:1 to receive an intravenous infusion of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or ipilimumab 3 mg/kg plus placebo, every 3 weeks for four doses. Subsequently, patients assigned to nivolumab plus ipilimumab received nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity, whereas patients allocated to ipilimumab alone received placebo every 2 weeks during this phase. Randomisation was done via an interactive voice response system with a permuted block schedule (block size of six) and stratification by BRAF mutation status. The study funder, patients, investigators, and study site staff were masked to treatment assignment. The primary endpoint, which has been reported previously, was the proportion of patients with BRAF V600 wild-type melanoma achieving an investigator-assessed objective response. Overall survival was an exploratory endpoint and is reported in this Article. Efficacy analyses were done on the intention-to-treat population, whereas safety was assessed in all treated patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT01927419, and is ongoing but no longer enrolling patients. Findings Between Sept 16, 2013, and Feb 6, 2014, we screened 179 patients and enrolled 142, randomly assigning 95 patients to nivolumab plus ipilimumab and 47 to ipilimumab alone. In each treatment group, one patient no longer met the study criteria following randomisation and thus did not receive study drug. At a median follow-up of 24·5 months (IQR 9·1–25·7), 2-year overall survival was 63·8% (95% CI 53·3–72·6) for those assigned to nivolumab plus ipilimumab and 53·6% (95% CI 38·1–66·8) for those assigned to ipilimumab alone; median overall survival had not been reached in either group (hazard ratio 0·74, 95% CI 0·43–1·26; p=0·26). Treatment-related grade 3–4 adverse events were reported in 51 (54%) of 94 patients who received nivolumab plus ipilimumab compared with nine (20%) of 46 patients who received ipilimumab alone. The most common treatment-related grade 3–4 adverse events were colitis (12 [13%] of 94 patients) and increased alanine aminotransferase (ten [11%]) in the combination group and diarrhoea (five [11%] of 46 patients) and hypophysitis (two [4%]) in the ipilimumab alone group. Serious grade 3–4 treatment-related adverse events were reported in 34 (36%) of 94 patients who received nivolumab plus ipilimumab (including colitis in ten [11%] of 94 patients, and diarrhoea in five [5%]) compared with four (9%) of 46 patients who received ipilimumab alone (including diarrhoea in two [4%] of 46 patients, colitis in one [2%], and hypophysitis in one [2%]). No new types of treatment-related adverse events or treatment-related deaths occurred in this updated analysis. Interpretation Although follow-up of the patients in this study is ongoing, the results of this analysis suggest that the combination of first-line nivolumab plus ipilimumab might lead to improved outcomes compared with first-line ipilimumab alone in patients with advanced melanoma. The results suggest encouraging survival outcomes with immunotherapy in this population of patients. Funding Bristol-Myers Squibb.

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

Abstract: Background Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS. Objective We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach. Secondarily, we aimed to match clusters to phenotypes. Methods In this multicenter case-control study patients with CRS and control subjects underwent surgery, and tissue was analyzed for IL-5, IFN-γ, IL-17A, TNF-α, IL-22, IL-1β, IL-6, IL-8, eosinophilic cationic protein, myeloperoxidase, TGF-β1, IgE, Staphylococcus aureus enterotoxin–specific IgE, and albumin. We used partition-based clustering. Results Clustering of 173 cases resulted in 10 clusters, of which 4 clusters with low or undetectable IL-5, eosinophilic cationic protein, IgE, and albumin concentrations, and 6 clusters with high concentrations of those markers. The group of IL-5–negative clusters, 3 clusters clinically resembled a predominant chronic rhinosinusitis without nasal polyps (CRSsNP) phenotype without increased asthma prevalence, and 1 cluster had a T H 17 profile and had mixed CRSsNP/CRSwNP. The IL-5–positive clusters were divided into a group with moderate IL-5 concentrations, a mixed CRSsNP/CRSwNP and increased asthma phenotype, and a group with high IL-5 levels, an almost exclusive nasal polyp phenotype with strongly increased asthma prevalence. In the latter group, 2 clusters demonstrated the highest concentrations of IgE and asthma prevalence, with all samples expressing Staphylococcus aureus enterotoxin–specific IgE. Conclusion Distinct CRS clusters with diverse inflammatory mechanisms largely correlated with phenotypes and further differentiated them and provided a more accurate description of the inflammatory mechanisms involved than phenotype information only.

Accurate first-principles structures and energies of diversely bonded systems from an efficient density functional

Abstract: One atom or molecule binds to another through various types of bond, the strengths of which range from several meV to several eV. Although some computational methods can provide accurate descriptions of all bond types, those methods are not efficient enough for many studies (for example, large systems, ab initio molecular dynamics and high-throughput searches for functional materials). Here, we show that the recently developed non-empirical strongly constrained and appropriately normed (SCAN) meta-generalized gradient approximation (meta-GGA) within the density functional theory framework predicts accurate geometries and energies of diversely bonded molecules and materials (including covalent, metallic, ionic, hydrogen and van der Waals bonds). This represents a significant improvement at comparable efficiency over its predecessors, the GGAs that currently dominate materials computation. Often, SCAN matches or improves on the accuracy of a computationally expensive hybrid functional, at almost-GGA cost. SCAN is therefore expected to have a broad impact on chemistry and materials science.

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis.

Abstract: Background The body of knowledge regarding rhinosinusitis(RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods Evidence-based reviews with recommendations(EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR)was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS)with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AECRS), and pediatric RS. Conclusion As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too often the foundation upon which these recommendations are based is comprised of lower level evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed.

A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle

Abstract: Muscle contraction depends on release of Ca2+ from the sarcoplasmic reticulum (SR) and reuptake by the Ca2+adenosine triphosphatase SERCA. We discovered a putative muscle-specific long noncoding RNA that encodes a peptide of 34 amino acids and that we named dwarf open reading frame (DWORF). DWORF localizes to the SR membrane, where it enhances SERCA activity by displacing the SERCA inhibitors, phospholamban, sarcolipin, and myoregulin. In mice, overexpression of DWORF in cardiomyocytes increases peak Ca2+ transient amplitude and SR Ca2+ load while reducing the time constant of cytosolic Ca2+ decay during each cycle of contraction-relaxation. Conversely, slow skeletal muscle lacking DWORF exhibits delayed Ca2+ clearance and relaxation and reduced SERCA activity. DWORF is the only endogenous peptide known to activate the SERCA pump by physical interaction and provides a means for enhancing muscle contractility.

Intelligence-Led Policing

Abstract: This paper is timely, given that policing is currently going through a period of significant change in both operational tactics and organisational structures. New ideas in crime reduction and changes to short- and long-term policing strategies are underway. Intelligence-led policing represents a recent approach and is one of the more prevalent of the current "shifts in crime control philosophy and policing practice" (Maguire 2000). Surprisingly, given the wide distribution of the term "intelligence-led policing", considerable confusion remains in regard to its actual meaning to both front-line officers and police management. This paper provides an introduction to intelligence-led policing and discusses some of the related limitations and opportunities. Adam Graycar Director Since the 1990s, "intelligence-led policing" (also known as intelligence-driven policing") has entered the lexicon of modern policing, especially in the UK and more recently Australia. Yet even with the ability of new ideas and innovation to spread throughout the policing world at the click of a mouse, there is still a lack of clarity among many in law enforcement as to what intelligence-led policing is, what it aims to achieve, and how it is supposed to operate. This can be seen in recent inspection reports of Her Majesty's Inspectorate of Constabulary (HMIC) in the UK (HMIC 2001, 2002), and in the lack of clarity regarding intelligence-led policing in the United States. A recent summit in March 2002 of over 120 criminal intelligence experts from across the US, funded by the US government and organised by the International Association of Chiefs of Police, may become a turning point in policing within the US. The participants called for a National Intelligence Plan, with one of the core recommendations being to "promote intelligence-led policing through a common understanding of criminal intelligence and its usefulness" (IACP 2002, p. v). The aspirations of the summit are considerable, but what is unclear from the summit report is a sound understanding of the aims of intelligence-led policing and its relationship to crime reduction. As intelligence-led policing is now a term in common usage within Australian law enforcement (a search of web pages and media releases found the term "intelligence-led" in all Australian police sites and the web site of the new Australian Crime Commission), it is timely to consider the origins of intelligence-led policing, the crime reduction levers it aims to pull, and the limitations and possibilities for this type of operational practice. Origins of Intelligence-led Policing Intelligence-led policing entered the police lexicon at some time around the early 1990s. As Gill (1998) has noted, the origins of intelligence-led policing are a little indistinct, but the earliest references to it originate in the UK where a seemingly inexorable rise in crime during the late 1980s and early 1990s coincided with increasing calls for police to be more effective and to be more cost-efficient. The driving forces for this move to a new strategy were both external and internal to policing. External drivers included an inability of the traditional, reactive model of policing to cope with the rapid changes in globalisation which have increased opportunities for transnational organised crime and removed physical and technological barriers across the policing domain. In the new "risk society" (Ericson & Haggerty 1997) the police were seen as the source of risk management data for a range of external institutions. With such an influence beyond the boundaries of law enforcement, it was never going to be long before the "new public management" drive to increase efficiency in public agencies reached the police. At the same time there was an internal recognition that changes were taking place in the dynamic relationship between the private security industry and the public police. …

Challenges in microbial ecology: building predictive understanding of community function and dynamics

Abstract: The importance of microbial communities (MCs) cannot be overstated. MCs underpin the biogeochemical cycles of the earth’s soil, oceans and the atmosphere, and perform ecosystem functions that impact plants, animals and humans. Yet our ability to predict and manage the function of these highly complex, dynamically changing communities is limited. Building predictive models that link MC composition to function is a key emerging challenge in microbial ecology. Here, we argue that addressing this challenge requires close coordination of experimental data collection and method development with mathematical model building. We discuss specific examples where model–experiment integration has already resulted in important insights into MC function and structure. We also highlight key research questions that still demand better integration of experiments and models. We argue that such integration is needed to achieve significant progress in our understanding of MC dynamics and function, and we make specific practical suggestions as to how this could be achieved.

Persistent HIV-1 replication maintains the tissue reservoir during therapy

Abstract: Lymphoid tissue is a key reservoir established by HIV-1 during acute infection. It is a site associated with viral production, storage of viral particles in immune complexes, and viral persistence. Although combinations of antiretroviral drugs usually suppress viral replication and reduce viral RNA to undetectable levels in blood, it is unclear whether treatment fully suppresses viral replication in lymphoid tissue reservoirs. Here we show that virus evolution and trafficking between tissue compartments continues in patients with undetectable levels of virus in their bloodstream. We present a spatial and dynamic model of persistent viral replication and spread that indicates why the development of drug resistance is not a foregone conclusion under conditions in which drug concentrations are insufficient to completely block virus replication. These data provide new insights into the evolutionary and infection dynamics of the virus population within the host, revealing that HIV-1 can continue to replicate and replenish the viral reservoir despite potent antiretroviral therapy.

Music interventions for improving psychological and physical outcomes in cancer patients

Abstract: Background Having cancer may result in extensive emotional, physical and social suffering. Music interventions have been used to alleviate symptoms and treatment side effects in cancer patients. Objectives To assess and compare the effects of music therapy and music medicine interventions for psychological and physical outcomes in people with cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), MEDLINE, Embase, CINAHL, PsycINFO, LILACS, Science Citation Index, CancerLit, CAIRSS, Proquest Digital Dissertations, ClinicalTrials.gov, Current Controlled Trials, the RILM Abstracts of Music Literature, http://www.wfmt.info/Musictherapyworld/ and the National Research Register. We searched all databases, except for the last two, from their inception to January 2016; the other two are no longer functional, so we searched them until their termination date. We handsearched music therapy journals, reviewed reference lists and contacted experts. There was no language restriction. Selection criteria We included all randomized and quasi-randomized controlled trials of music interventions for improving psychological and physical outcomes in adult and pediatric patients with cancer. We excluded participants undergoing biopsy and aspiration for diagnostic purposes. Data collection and analysis Two review authors independently extracted the data and assessed the risk of bias. Where possible, we presented results in meta-analyses using mean differences and standardized mean differences. We used post-test scores. In cases of significant baseline difference, we used change scores. Main results We identified 22 new trials for inclusion in this update. In total, the evidence of this review rests on 52 trials with a total of 3731 participants. We included music therapy interventions offered by trained music therapists, as well as music medicine interventions, which are defined as listening to pre-recorded music, offered by medical staff. We categorized 23 trials as music therapy trials and 29 as music medicine trials. The results suggest that music interventions may have a beneficial effect on anxiety in people with cancer, with a reported average anxiety reduction of 8.54 units (95% confidence interval (CI) −12.04 to −5.05, P < 0.0001) on the Spielberger State Anxiety Inventory - State Anxiety (STAI-S) scale (range 20 to 80) and −0.71 standardized units (13 studies, 1028 participants; 95% CI −0.98 to −0.43, P < 0.00001; low quality evidence) on other anxiety scales, a moderate to strong effect. Results also suggested a moderately strong, positive impact on depression (7 studies, 723 participants; standardized mean difference (SMD): −0.40, 95% CI −0.74 to −0.06, P = 0.02; very low quality evidence), but because of the very low quality of the evidence for this outcome, this result needs to be interpreted with caution. We found no support for an effect of music interventions on mood or distress. Music interventions may lead to small reductions in heart rate, respiratory rate and blood pressure but do not appear to impact oxygen saturation level. We found a large pain-reducing effect (7 studies, 528 participants; SMD: −0.91, 95% CI −1.46 to −0.36, P = 0.001, low quality evidence). In addition, music interventions had a small to moderate treatment effect on fatigue (6 studies, 253 participants; SMD: −0.38, 95% CI −0.72 to −0.04, P = 0.03; low quality evidence), but we did not find strong evidence for improvement in physical functioning. The results suggest a large effect of music interventions on patients' quality of life (QoL), but the results were highly inconsistent across studies, and the pooled effect size for the music medicine and music therapy studies was accompanied by a large confidence interval (SMD: 0.98, 95% CI −0.36 to 2.33, P = 0.15, low quality evidence). A comparison between music therapy and music medicine interventions suggests a moderate effect of music therapy interventions for patients' quality of life (QoL) (3 studies, 132 participants; SMD: 0.42, 95% CI 0.06 to 0.78, P = 0.02; very low quality evidence), but we found no evidence of an effect for music medicine interventions. A comparison between music therapy and music medicine studies was also possible for anxiety, depression and mood, but we found no difference between the two types of interventions for these outcomes. The results of single studies suggest that music listening may reduce the need for anesthetics and analgesics as well as decrease recovery time and duration of hospitalization, but more research is needed for these outcomes. We could not draw any conclusions regarding the effect of music interventions on immunologic functioning, coping, resilience or communication outcomes because either we could not pool the results of the studies that included these outcomes or we could only identify one trial. For spiritual well-being, we found no evidence of an effect in adolescents or young adults, and we could not draw any conclusions in adults. The majority of studies included in this review update presented a high risk of bias, and therefore the quality of evidence is low. Authors' conclusions This systematic review indicates that music interventions may have beneficial effects on anxiety, pain, fatigue and QoL in people with cancer. Furthermore, music may have a small effect on heart rate, respiratory rate and blood pressure. Most trials were at high risk of bias and, therefore, these results need to be interpreted with caution.

DeepSaliency: Multi-Task Deep Neural Network Model for Salient Object Detection

Abstract: A key problem in salient object detection is how to effectively model the semantic properties of salient objects in a data-driven manner. In this paper, we propose a multi-task deep saliency model based on a fully convolutional neural network with global input (whole raw images) and global output (whole saliency maps). In principle, the proposed saliency model takes a data-driven strategy for encoding the underlying saliency prior information, and then sets up a multi-task learning scheme for exploring the intrinsic correlations between saliency detection and semantic image segmentation. Through collaborative feature learning from such two correlated tasks, the shared fully convolutional layers produce effective features for object perception. Moreover, it is capable of capturing the semantic information on salient objects across different levels using the fully convolutional layers, which investigate the feature-sharing properties of salient object detection with a great reduction of feature redundancy. Finally, we present a graph Laplacian regularized nonlinear regression model for saliency refinement. Experimental results demonstrate the effectiveness of our approach in comparison with the state-of-the-art approaches.

Cavity-Controlled Chemistry in Molecular Ensembles

Abstract: The demonstration of strong and ultrastrong coupling regimes of cavity QED with polyatomic molecules has opened new routes to control chemical dynamics at the nanoscale. We show that strong resonant coupling of a cavity field with an electronic transition can effectively decouple collective electronic and nuclear degrees of freedom in a disordered molecular ensemble, even for molecules with high-frequency quantum vibrational modes having strong electron-vibration interactions. This type of polaron decoupling can be used to control chemical reactions. We show that the rate of electron transfer reactions in a cavity can be orders of magnitude larger than in free space for a wide class of organic molecular species.

Dual-Function Radar-Communications: Information Embedding Using Sidelobe Control and Waveform Diversity

Abstract: We develop a new technique for a dual-function system with joint radar and communication platforms. Sidelobe control of the transmit beamforming in tandem with waveform diversity enables communication links using the same pulse radar spectrum. Multiple simultaneously transmitted orthogonal waveforms are used for embedding a sequence of LB bits during each radar pulse. Two weight vectors are designed to achieve two transmit spatial power distribution patterns, which have the same main radar beam, but differ in sidelobe levels towards the intended communication receivers. The receiver interpretation of the bit is based on its radiated beam. The proposed technique allows information delivery to single or multiple communication directions outside the mainlobe of the radar. It is shown that the communication process is inherently secure against intercept from directions other than the pre-assigned communication directions. The employed waveform diversity scheme supports a multiple-input multiple-output radar operation mode. The performance of the proposed technique is investigated in terms of the bit error rate.

The Role of Customer Engagement in Building Consumer Loyalty to Tourism Brands

Abstract: Customer engagement has recently emerged in both academic literature and practitioner discussions as a brand loyalty predictor that may be superior to other traditional loyalty antecedents. However, empirical inquiry on customer engagement is relatively scarce. As tourism and hospitality firms have widely adopted customer engagement strategies for managing customer–brand relationships, further understanding of this concept is essential. Using structural equation modeling, this study investigates the linkages of customer engagement with traditional antecedents of brand loyalty. Results based on 496 hotel and airline customers suggest that customer engagement enhances customers’ service brand evaluation, brand trust, and brand loyalty. The results show that service brand loyalty can be strengthened not only through the service consumption experience but also through customer engagement beyond the service encounter. This study contributes to the literature by providing an empirical evaluation of the relation...

Versatile van der Waals Density Functional Based on a Meta-Generalized Gradient Approximation

Abstract: Van der Waals interactions are ubiquitous in different materials yet not always described properly by current theories. Now, researchers have determined how to accurately and efficiently treat long-range Van der Waals interactions together with other chemical bonds, new findings that are important for studies of layered materials.

Digital product innovation within four classes of innovation networks

Abstract: The increased digitization of organizational processes and products poses new challenges for understanding product innovation. It also opens new horizons for information systems research. We analyse how ongoing pervasive digitization of product innovation reshapes knowledge creation and sharing in innovation networks. We argue that advances in digital technologies 1 increase innovation network connectivity by reducing communication costs and increasing its reach and scope and 2 increase the speed and scope of digital convergence, which increases network knowledge heterogeneity and need for integration. These developments, in turn, stretch existing innovation networks by redistributing control and increasing the demand for knowledge coordination across time and space presenting novel challenges for knowledge creation, assimilation and integration. Based on this foundation, we distinguish four types of emerging innovation networks supported by digitalization: 1 project innovation networks; 2 clan innovation networks; 3 federated innovation networks; and 4 anarchic innovation networks. Each network involves different cognitive and social translations - or ways of identifying, sharing and assimilating knowledge. We describe the role of five novel properties of digital infrastructures in supporting each type of innovation network: representational flexibility, semantic coherence, temporal and spatial traceability, knowledge brokering and linguistic calibration. We identify several implications for future innovation research. In particular, we focus on the emergence of anarchic network forms that follow full-fledged digital convergence founded on richer innovation ontologies and epistemologies calling to critically re-examine the nature and impact of modularization for innovation.

Fundamental constructs in food parenting practices: A content map to guide future research

Abstract: Although research shows that "food parenting practices" can impact children's diet and eating habits, current understanding of the impact of specific practices has been limited by inconsistencies in terminology and definitions. This article represents a critical appraisal of food parenting practices, including clear terminology and definitions, by a working group of content experts. The result of this effort was the development of a content map for future research that presents 3 overarching, higher-order food parenting constructs--coercive control, structure, and autonomy support--as well as specific practice subconstructs. Coercive control includes restriction, pressure to eat, threats and bribes, and using food to control negative emotions. Structure includes rules and limits, limited/guided choices, monitoring, meal- and snacktime routines, modeling, food availability and accessibility, food preparation, and unstructured practices. Autonomy support includes nutrition education, child involvement, encouragement, praise, reasoning, and negotiation. Literature on each construct is reviewed, and directions for future research are offered. Clear terminology and definitions should facilitate cross-study comparisons and minimize conflicting findings resulting from previous discrepancies in construct operationalization.

Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals

Abstract: Although Neandertal sequences that persist in the genomes of modern humans have been identified in Eurasians, comparable studies in people whose ancestors hybridized with both Neandertals and Denisovans are lacking. We developed an approach to identify DNA inherited from multiple archaic hominin ancestors and applied it to whole-genome sequences from 1523 geographically diverse individuals, including 35 previously unknown Island Melanesian genomes. In aggregate, we recovered 1.34 gigabases and 303 megabases of the Neandertal and Denisovan genome, respectively. We use these maps of archaic sequences to show that Neandertal admixture occurred multiple times in different non-African populations, characterize genomic regions that are significantly depleted of archaic sequences, and identify signatures of adaptive introgression.