Publications by authors named "Moser R"

826 Publications

Access-Based Services for the Base of the Pyramid.

J Serv Res 2018 Nov 22;21(4):421-437. Epub 2018 Apr 22.

University of St. Gallen, St. Gallen, Switzerland.

One key challenge for consumers at the base of the pyramid (BoP) is access to products that could transform their livelihood, leading to nonconsumption as the dominant pattern. Previous studies have claimed that nonconsumption could be addressed with services offering access to goods without ownership. Drawing on expected utility theory, we conduct two experimental studies in rural India that provide the first empirical support for the idea that the availability of access-based services reduces nonconsumption at the BoP. Additionally, we show that this effect is explained by BoP consumers' expected utility assessment as reflected in their perception of access being more affordable and entailing less financial risk than ownership. We also demonstrate that access temporality, an important configurational variable for access-based service providers, affects the degree to which nonconsumption can be decreased. Compared to short-term access, BoP consumers perceive long-term access to be too similar to ownership in terms of affordability and financial risk, which causes them to refrain from purchasing. Overall, the results suggest that access-based services represent a viable alternative for addressing nonconsumption at the BoP. However, service providers should be aware that short-term access is required to gain acceptance among BoP consumers.
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http://dx.doi.org/10.1177/1094670518770034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174633PMC
November 2018

Selective Neuronal Uptake and Distribution of AAVrh8, AAV9, and AAVrh10 in Sheep After Intra-Striatal Administration.

J Huntingtons Dis 2018 ;7(4):309-319

Department of Medicine and RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.

Background: Transgenic sheep are currently the only large animal model of Huntington's disease expressing full-length mutant human huntingtin. These transgenic sheep provide an opportunity to test adeno associated virus (AAV) therapies directly targeting the huntingtin gene. A recent study demonstrated that self-complementary (sc) AAV with artificial miRNA against human huntingtin reduced mutant human huntingtin in caudate and putamen after a single injection near the internal capsule.

Objective: To identify an AAV serotype among AAVrh8, AAV9 and AAVrh10 with the highest neuronal uptake and distribution, with no obvious cell loss in the neostriatum of the sheep.

Methods: We tested AAVrh8, AAV9 and AAVrh10 by stereotactic direct unilateral injection into the neostriatum of sheep, near the internal capsule. Four weeks after administration, we examined the viral spread and neuronal uptake of each serotype of AAV containing GFP. We compared single stranded (ss) and scAAVs. Further, we measured the distribution of AAVrh8 and AAV9 to a variety of tissues outside the brain.

Results: Sc AAV9 had the best combination of neuronal uptake and distribution throughout the neostriatum. scAAVrh10 demonstrated good spread, but was not taken up by neurons. scAAVrh8 demonstrated good spread, but had less neuronal uptake than AAV9. Six hours after convection-enhanced administration to the neostriatum, both AAVrh8 and AAV9 viral genomes were detected in blood, saliva, urine, feces and wool. By four weeks, viral genomes were detected in wool only. Administration of AAVrh8, AAV9 and AAVrh10 was not associated with loss of neostriatal, medium spiny neuron number as measured by DARPP32 immunohistochemistry.

Conclusions: Altogether, we found scAAV9 had the best neuronal uptake and spread, showed no loss of neurons at one-month post-injection, and was not measurable in body fluids one month after injection. This information will guide future clinical experiments requiring brain injection of AAV for therapeutics for gene or miRNA deliveries in sheep transgenic for the human huntingtin gene.
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http://dx.doi.org/10.3233/JHD-180302DOI Listing
October 2019

Diagnosis and Management of Mild Traumatic Brain Injury in Children: A Systematic Review.

JAMA Pediatr 2018 11 5;172(11):e182847. Epub 2018 Nov 5.

John H. Stroger Jr. Hospital of Cook County, Chicago, Illinois.

Importance: In recent years, there has been an exponential increase in the research guiding pediatric mild traumatic brain injury (mTBI) clinical management, in large part because of heightened concerns about the consequences of mTBI, also known as concussion, in children. The CDC National Center for Injury Prevention and Control's (NCIPC) Board of Scientific Counselors (BSC), a federal advisory committee, established the Pediatric Mild TBI Guideline workgroup to complete this systematic review summarizing the first 25 years of literature in this field of study.

Objective: To conduct a systematic review of the pediatric mTBI literature to serve as the foundation for an evidence-based guideline with clinical recommendations associated with the diagnosis and management of pediatric mTBI.

Evidence Review: Using a modified Delphi process, the authors selected 6 clinical questions on diagnosis, prognosis, and management or treatment of pediatric mTBI. Two consecutive searches were conducted on PubMed, Embase, ERIC, CINAHL, and SportDiscus. The first included the dates January 1, 1990, to November 30, 2012, and an updated search included December 1, 2012, to July 31, 2015. The initial search was completed from December 2012 to January 2013; the updated search, from July 2015 to August 2015. Two authors worked in pairs to abstract study characteristics independently for each article selected for inclusion. A third author adjudicated disagreements. The risk of bias in each study was determined using the American Academy of Neurology Classification of Evidence Scheme. Conclusion statements were developed regarding the evidence within each clinical question, and a level of confidence in the evidence was assigned to each conclusion using a modified GRADE methodology. Data analysis was completed from October 2014 to May 2015 for the initial search and from November 2015 to April 2016 for the updated search.

Findings: Validated tools are available to assist clinicians in the diagnosis and management of pediatric mTBI. A significant body of research exists to identify features that are associated with more serious TBI-associated intracranial injury, delayed recovery from mTBI, and long-term sequelae. However, high-quality studies of treatments meant to improve mTBI outcomes are currently lacking.

Conclusions And Relevance: This systematic review was used to develop an evidence-based clinical guideline for the diagnosis and management of pediatric mTBI. While an increasing amount of research provides clinically useful information, this systematic review identified key gaps in diagnosis, prognosis, and management.
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http://dx.doi.org/10.1001/jamapediatrics.2018.2847DOI Listing
November 2018

Centers for Disease Control and Prevention Guideline on the Diagnosis and Management of Mild Traumatic Brain Injury Among Children.

JAMA Pediatr 2018 11 5;172(11):e182853. Epub 2018 Nov 5.

John H. Stroger, Jr Hospital of Cook County (formerly Cook County Hospital), Chicago, Illinois.

Importance: Mild traumatic brain injury (mTBI), or concussion, in children is a rapidly growing public health concern because epidemiologic data indicate a marked increase in the number of emergency department visits for mTBI over the past decade. However, no evidence-based clinical guidelines have been developed to date for diagnosing and managing pediatric mTBI in the United States.

Objective: To provide a guideline based on a previous systematic review of the literature to obtain and assess evidence toward developing clinical recommendations for health care professionals related to the diagnosis, prognosis, and management/treatment of pediatric mTBI.

Evidence Review: The Centers for Disease Control and Prevention (CDC) National Center for Injury Prevention and Control Board of Scientific Counselors, a federal advisory committee, established the Pediatric Mild Traumatic Brain Injury Guideline Workgroup. The workgroup drafted recommendations based on the evidence that was obtained and assessed within the systematic review, as well as related evidence, scientific principles, and expert inference. This information includes selected studies published since the evidence review was conducted that were deemed by the workgroup to be relevant to the recommendations. The dates of the initial literature search were January 1, 1990, to November 30, 2012, and the dates of the updated literature search were December 1, 2012, to July 31, 2015.

Findings: The CDC guideline includes 19 sets of recommendations on the diagnosis, prognosis, and management/treatment of pediatric mTBI that were assigned a level of obligation (ie, must, should, or may) based on confidence in the evidence. Recommendations address imaging, symptom scales, cognitive testing, and standardized assessment for diagnosis; history and risk factor assessment, monitoring, and counseling for prognosis; and patient/family education, rest, support, return to school, and symptom management for treatment.

Conclusions And Relevance: This guideline identifies the best practices for mTBI based on the current evidence; updates should be made as the body of evidence grows. In addition to the development of the guideline, CDC has created user-friendly guideline implementation materials that are concise and actionable. Evaluation of the guideline and implementation materials is crucial in understanding the influence of the recommendations.
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http://dx.doi.org/10.1001/jamapediatrics.2018.2853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006878PMC
November 2018

Role of Stone-Wales defects on the interfacial interactions among graphene, carbon nanotubes, and Nylon 6: A first-principles study.

J Chem Phys 2018 Aug;149(5):054703

School of Polymer Science and Engineering, The University of Southern Mississippi, Hattiesburg, Mississippi 39406, USA.

We investigate computationally the role of Stone-Wales (SW) defects on the interfacial interactions among graphene, carbon nanotubes (CNTs), and Nylon 6 using density functional theory (DFT) and the empirical force-field. Our first-principles DFT calculations were performed using the Quantum ESPRESSO electronic structure code with the highly accurate van der Waals functional (vdW-DF2). Both pristine and SW-defected carbon nanomaterials were investigated. The computed results show that the presence of SW defects on CNTs weakens the CNT-graphene interactions. Our result that CNT-graphene interaction is much stronger than CNT-CNT interaction indicates that graphene would be able to promote the dispersion of CNTs in the polymer matrix. Our results demonstrate that carbon nanomaterials form stable complexes with Nylon 6 and that the van der Waals interactions, as revealed by the electronic charge density difference maps, play a key stabilizing role on the interfacial interactions among graphene, CNTs, and Nylon 6. Using the density of states calculations, we observed that the bandgaps of graphene and CNTs were not significantly modified due to their interactions with Nylon 6. The Young's moduli of complexes were found to be the averages of the moduli of their individual constituents.
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http://dx.doi.org/10.1063/1.5032081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910596PMC
August 2018

Functional Precision Medicine Identifies Novel Druggable Targets and Therapeutic Options in Head and Neck Cancer.

Clin Cancer Res 2018 06 29;24(12):2828-2843. Epub 2018 Mar 29.

Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with high mortality and a lack of targeted therapies. To identify and prioritize druggable targets, we performed genome analysis together with genome-scale siRNA and oncology drug profiling using low-passage tumor cells derived from a patient with treatment-resistant HPV-negative HNSCC. A tumor cell culture was established and subjected to whole-exome sequencing, RNA sequencing, comparative genome hybridization, and high-throughput phenotyping with a siRNA library covering the druggable genome and an oncology drug library. Secondary screens of candidate target genes were performed on the primary tumor cells and two nontumorigenic keratinocyte cell cultures for validation and to assess cancer specificity. siRNA screens of the kinome on two isogenic pairs of p53-mutated HNSCC cell lines were used to determine generalizability. Clinical utility was addressed by performing drug screens on two additional HNSCC cell cultures derived from patients enrolled in a clinical trial. Many of the identified copy number aberrations and somatic mutations in the primary tumor were typical of HPV(-) HNSCC, but none pointed to obvious therapeutic choices. In contrast, siRNA profiling identified 391 candidate target genes, 35 of which were preferentially lethal to cancer cells, most of which were not genomically altered. Chemotherapies and targeted agents with strong tumor-specific activities corroborated the siRNA profiling results and included drugs that targeted the mitotic spindle, the proteasome, and G-M kinases and We also show the feasibility of drug profiling for patients enrolled in a clinical trial. High-throughput phenotyping with siRNA and drug libraries using patient-derived tumor cells prioritizes mutated driver genes and identifies novel drug targets not revealed by genomic profiling. Functional profiling is a promising adjunct to DNA sequencing for precision oncology. .
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http://dx.doi.org/10.1158/1078-0432.CCR-17-1339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004257PMC
June 2018

Gender Differences in Symptom Reporting on Baseline Sport Concussion Testing Across the Youth Age Span.

Arch Clin Neuropsychol 2019 Feb;34(1):50-59

Saint Joseph's University, Philadelphia, PA, USA.

Background: Little is known regarding gender differences in concussion symptom reporting developmentally across the age span, specifically in pre-adolescent athletes. The present study asks: Do boys and girls differ in symptom reporting across the pre-adolescent to post-adolescent age span?

Method: This retrospective study utilized baseline assessments from 11,695 10-22 year-old athletes assigned to 3 independent groups: Pre-adolescent 10-12 year olds (n = 1,367; 12%), Adolescent 13-17 year olds (n = 2,974; 25%), and Late Adolescent 18-22 year olds (n = 7,354; 63%). Males represented 60% of the sample. Baseline ImPACT composite scores and Post-Concussion Symptom Scale scores (Total, Physical, Cognitive, Emotional, Sleep) were analyzed for the effects of age and gender.

Results: Statistically significant main effects were found for age and gender on all ImPACT composites, Total Symptoms, and Symptom factors. Significant interaction effects were noted between age and gender for all ImPACT composites, Total Symptoms, and Symptom factors. Total Symptoms and all Symptom factors were highest in adolescents (ages 13-17) for males and females. In the 10-12 age group, females displayed lower Total Symptoms, Physical, and Sleep factors than males.

Conclusion: The notion of females being more likely than males to report symptoms does not appear to apply across the developmental age span, particularly prior to adolescence. Females show greater emotional endorsement across the youth age span (10-22 years). Adolescence (13-17 years) appears to be a time of increased symptomatology that may lessen after the age of 18.
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http://dx.doi.org/10.1093/arclin/acy007DOI Listing
February 2019

Structure, property, and function of sheepshead (Archosargus probatocephalus) teeth.

Arch Oral Biol 2018 May 2;89:1-8. Epub 2018 Feb 2.

Department of Mechanical Engineering, Mississippi State University, Mississippi State, MS 39762, USA; Center for Advanced Vehicular Systems, Mississippi State University, Mississippi State, MS 39762, USA.

Objectives: This paper studies A. probatocephalus teeth and investigates the mechanical properties and chemical composition of the enameloid and dentin.

Design: Nanoindentation tests with a max load of 1000 μN and X-ray Energy Dispersive Spectroscopy (EDS) were performed along the diameter of the polished sample. Microstructural analysis of the dentin tubules was performed from SEM images.

Results: From nanoindentation testing, the dentin of the sheepshead teeth has a nanoindentation hardness of 0.89 ± 0.21 (mean ± S.D.) GPa and a reduced Young's modulus of 23.29 ± 5.30 GPa. The enameloid of A. probatocephalus has a hardness of 4.36 ± 0.44 GPa and a mean reduced Young's modulus of 98.14 ± 6.91 GPa. Additionally, nanoindentation tests showed that the enameloid's hardness and modulus increased closer to the surface of the tooth. X-ray Energy Dispersive Spectroscopy (EDS) data further suggests that the gradient may be a result of the wt% fluoride within the enameloid, where an increase in fluoride results in an increase in reduced Young's modulus and hardness.

Conclusion: The microstructural characterization of the number density and area of the dentin tubules were used to address the porosity effect in the dentin to achieve the experimentally validated microhardness. The mechanical properties of the sheepshead teeth were also compared with previous nanoindentation tests from other aquatic species. The sheepshead teeth exhibit a greater reduced Young's modulus and hardness compared to shark and piranha teeth.
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http://dx.doi.org/10.1016/j.archoralbio.2018.01.013DOI Listing
May 2018

Tobacco Use Among Adults by Sexual Orientation: Findings from the Population Assessment of Tobacco and Health Study.

LGBT Health 2018 01;5(1):33-44

1 Behavioral Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute , Bethesda, Maryland.

Purpose: The aim of this study was to characterize lifetime tobacco use across two measures of sexual orientation and six types of tobacco products.

Methods: We conducted a cross-sectional analysis of the Population Assessment of Tobacco and Health (Wave 1, 2013-2014, USA) to estimate the prevalence of tobacco use (cigarettes, e-cigarettes, cigars, pipes, hookah, and smokeless) stratified by gender (men/women), age (< 25/≥ 25 years old), and sexual orientation. Sexual orientation was operationalized as sexual identity and sexual attraction.

Results: Younger lesbian/gay and bisexual women had higher relative odds of experimental use of all six tobacco products compared to heterosexual women, whereas lesbian/gay and bisexual women in both age groups had higher odds of regular use of cigarettes, e-cigarettes, cigars, and hookah than heterosexual women. Younger gay men (but not older gay men) had higher relative odds of experimental and regular use of cigarettes compared to heterosexual men. Older gay men had higher odds of experimental e-cigarette and hookah use, but lower odds of regular cigar and experimental/regular smokeless tobacco use. Measures of sexual orientation identity and sexual attraction resulted in similar estimates of tobacco use with noted differences in those who identified as "something else," as well as among those who indicated asexual attraction.

Conclusion: Our findings reflect a complex relationship between sexual orientation and tobacco use. Gender-based and product-specific approaches to tobacco prevention and control efforts are needed to address the high use of tobacco among sexual minority women.
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http://dx.doi.org/10.1089/lgbt.2017.0175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802250PMC
January 2018

A bio-conjugated chitosan wrapped CNT based 3D nanoporous architecture for separation and inactivation of Rotavirus and Shigella waterborne pathogens.

J Mater Chem B 2017 Dec 30;5(48):9522-9531. Epub 2017 Nov 30.

Department of Chemistry and Biochemistry, Jackson State University, Jackson, MS, USA.

The United Nations (UN) estimates that more than one billion people in this world do not have access to safe drinking water due to microbial hazards and it kills more than 7.6 million children every year via waterborne diseases. Driven by the need for the removal and inactivation of waterborne pathogens in drinking water, we report the chemical design and details of microscopic characterization of a bio-conjugated chitosan attached carbon nanotube based three dimensional (3D) nanoporous architecture, which has the capability for effective separation and complete disinfection of waterborne pathogens from environmental water samples. In the reported design, chitosan, a biodegradable antimicrobial polysaccharide with an architecture-forming ability has been used for the formation of 3D pores as channels for water passage, as well as to increase the permeability on the inner and outer architectures for killing Rotavirus and Shigella waterborne pathogens. On the other hand, due to their large surface area, CNTs have been wrapped by chitosan to enhance the adsorption capability of the architecture for the separation and removal of pathogens from water. The reported data show that the anti-Rotavirus VP7 antibody and LL-37 antimicrobial peptide conjugated chitosan-CNT architecture can be used for efficient separation, identification and 100% eradication of Rotavirus and Shigella waterborne pathogens from water samples of different sources. A detailed mechanism for the separation and inactivation of waterborne pathogens using the bio-conjugated chitosan based 3D architecture has been discussed using microscopic and spectroscopic studies. Reported experimental data demonstrate that the multifunctional bio-conjugated 3D architecture has good potential for use in waterborne pathogen separation and inactivation technology.
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http://dx.doi.org/10.1039/c7tb02815fDOI Listing
December 2017

Artificial miRNAs Reduce Human Mutant Huntingtin Throughout the Striatum in a Transgenic Sheep Model of Huntington's Disease.

Hum Gene Ther 2018 06 23;29(6):663-673. Epub 2018 Feb 23.

1 Department of Medicine, University of Massachusetts Medical School , Worcester, Massachusetts.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a genetic expansion of the CAG repeat region in the huntingtin (HTT) gene. Studies in HD mouse models have shown that artificial miRNAs can reduce mutant HTT, but evidence for their effectiveness and safety in larger animals is lacking. HD transgenic sheep express the full-length human HTT with 73 CAG repeats. AAV9 was used to deliver unilaterally to HD sheep striatum an artificial miRNA targeting exon 48 of the human HTT mRNA under control of two alternative promoters: U6 or CβA. The treatment reduced human mutant (m) HTT mRNA and protein 50-80% in the striatum at 1 and 6 months post injection. Silencing was detectable in both the caudate and putamen. Levels of endogenous sheep HTT protein were not affected. There was no significant loss of neurons labeled by DARPP32 or NeuN at 6 months after treatment, and Iba1-positive microglia were detected at control levels. It is concluded that safe and effective silencing of human mHTT protein can be achieved and sustained in a large-animal brain by direct delivery of an AAV carrying an artificial miRNA.
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http://dx.doi.org/10.1089/hum.2017.199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909722PMC
June 2018

The Age Variable in Childhood Concussion Management: A Systematic Review.

Arch Clin Neuropsychol 2018 Jun;33(4):417-426

Saint. Joseph's University, Philadelphia, PA, USA.

Background: Sports-related concussion in young children has become a significant international public health issue. This paper reviews the research literature in an effort to shed light on the question, "At what age should young children be managed differently than adults or older adolescents?"

Method: A systematic review, registered with PROSPERO and using PRISMA guidelines, was conducted rendering 37 sports concussion original research studies that examined age as a variable (5-18 years), and which met specific inclusion/exclusion criteria.

Findings: There are no defined, evidence-based age groups for childhood concussion to substantiate differential management across the childhood and adolescent age span. There is evidence to support: (1) concussion may present differently across developmental stages; (2) with increasing age, adolescents may exhibit more symptoms from concussion; (3) the age range of 12-13 is the most frequently used cutoff point between younger and older children; (4) sports concussion research has classified the age variable in children in a number of manners: educational, developmental, sport level, or as a continuous variable, or matter of sample convenience; and (5) four general groupings of young versus pre-puberty child and early versus late adolescent are often utilized.

Conclusions: Due to limited measures and challenges of assessing younger children, current research presents a limited understanding of childhood concussion. Studies in children often lack explained rationales or theories behind age groupings or cutoffs. There is a need for studies dedicated to the question of how concussion varies developmentally from preschool through late adolescence to guide diagnosis and management.
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http://dx.doi.org/10.1093/arclin/acx070DOI Listing
June 2018

Instant tough bonding of hydrogels for soft machines and electronics.

Sci Adv 2017 06 21;3(6):e1700053. Epub 2017 Jun 21.

Linz Institute of Technology, Soft Electronics Laboratory, Johannes Kepler University Linz, 4040 Linz, Austria.

Introducing methods for instant tough bonding between hydrogels and antagonistic materials-from soft to hard-allows us to demonstrate elastic yet tough biomimetic devices and machines with a high level of complexity. Tough hydrogels strongly attach, within seconds, to plastics, elastomers, leather, bone, and metals, reaching unprecedented interfacial toughness exceeding 2000 J/m. Healing of severed ionic hydrogel conductors becomes feasible and restores function instantly. Soft, transparent multilayered hybrids of elastomers and ionic hydrogels endure biaxial strain with more than 2000% increase in area, facilitating soft transducers, generators, and adaptive lenses. We demonstrate soft electronic devices, from stretchable batteries, self-powered compliant circuits, and autonomous electronic skin for triggered drug delivery. Our approach is applicable in rapid prototyping and in delicate environments inaccessible for extended curing and cross-linking.
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http://dx.doi.org/10.1126/sciadv.1700053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5479648PMC
June 2017

Synergy between Prkdc and Trp53 regulates stem cell proliferation and GI-ARS after irradiation.

Cell Death Differ 2017 11 7;24(11):1853-1860. Epub 2017 Jul 7.

Division of Human Biology Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, Seattle WA 98109, USA.

Ionizing radiation (IR) is one of the most widely used treatments for cancer. However, acute damage to the gastrointestinal tract or gastrointestinal acute radiation syndrome (GI-ARS) is a major dose-limiting side effect, and the mechanisms that underlie this remain unclear. Here we use mouse models to explore the relative roles of DNA repair, apoptosis, and cell cycle arrest in radiation response. IR induces DNA double strand breaks and DNA-PK mutant Prkdc mice are sensitive to GI-ARS due to an inability to repair these breaks. IR also activates the tumor suppressor p53 to trigger apoptotic cell death within intestinal crypt cells and p53 deficient mice are resistant to apoptosis. To determine if DNA-PK and p53 interact to govern radiosensitivity, we compared the response of single and compound mutant mice to 8 Gy IR. Compound mutant Prkdc/Trp53mice died earliest due to severe GI-ARS. While both Prkdc and Prkdc/Trp53mutant mice had higher levels of IR-induced DNA damage, particularly within the stem cell compartment of the intestinal crypt, in Prkdc/Trp53mice these damaged cells abnormally progressed through the cell cycle resulting in mitotic cell death. This led to a loss of Paneth cells and a failure to regenerate the differentiated epithelial cells required for intestinal function. IR-induced apoptosis did not correlate with radiosensitivity. Overall, these data reveal that DNA repair, mediated by DNA-PK, and cell cycle arrest, mediated by p53, cooperate to protect the stem cell niche after DNA damage, suggesting combination approaches to modulate both pathways may be beneficial to reduce GI-ARS. As many cancers harbor p53 mutations, this also suggests targeting DNA-PK may be effective to enhance sensitivity of p53 mutant tumors to radiation.
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http://dx.doi.org/10.1038/cdd.2017.107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635213PMC
November 2017

Increased Symptom Reporting in Young Athletes Based on History of Previous Concussions.

Dev Neuropsychol 2017 5;42(4):276-283. Epub 2017 Jul 5.

b Department of Psychology , Saint Joseph's University , Philadelphia , Pennsylvania.

Research documents increased symptoms in adolescents with a history of two or more concussions. This study examined baseline evaluations of 2,526 younger athletes, ages 10 to 14. Between-groups analyses examined Post Concussion Symptom Scale symptoms by concussion history group (None, One, Two+) and clusters of Physical, Cognitive, Emotional, and Sleep symptoms. Healthy younger athletes with a concussion history reported greater physical, emotional, and sleep-related symptoms than those with no history of concussion, with a greater endorsement in physical/sleep symptom clusters. Findings suggest younger athletes with a history of multiple concussions may experience residual symptoms.
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http://dx.doi.org/10.1080/87565641.2017.1334785DOI Listing
December 2017

Cyclic deformation and fatigue data for Ti-6Al-4V ELI under variable amplitude loading.

Data Brief 2017 Aug 19;13:180-186. Epub 2017 May 19.

US Army Engineer Research and Development Center, Vicksburg, MS 39180, USA.

This article presents the strain-based experimental data for Ti-6Al-4V ELI under non-constant amplitude cyclic loading. Uniaxial strain-controlled fatigue experiments were conducted under three different loading conditions, including two-level block loading (i.e. high-low and low-high), periodic overload, and variable amplitude loading. Tests were performed under fully-reversed, and mean strain/stress conditions. For each test conducted, two sets of data were collected; the cyclic stress-strain response (i.e. hysteresis loops) in log increments, and the peak and valley values of stress and strain for each cycle. Residual fatigue lives are reported for tests with two-level block loading, while for periodic overload and variable amplitude experiments, fatigue lives are reported in terms of number of blocks to failure.
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http://dx.doi.org/10.1016/j.dib.2017.05.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458061PMC
August 2017

Access to Electronic Personal Health Records Among Patients With Multiple Chronic Conditions: A Secondary Data Analysis.

J Med Internet Res 2017 06 2;19(6):e188. Epub 2017 Jun 2.

Behavioral Research Program, National Cancer Institute, Bethesda, MD, United States.

Background: In the United States, national incentives for offering access to electronic personal health records (ePHRs) through electronic means are geared toward creating a culture of patient engagement. One group of patients who stand to benefit from online access to ePHRs is the growing population with multiple chronic conditions (MCC). However, little is known about the current availability and use of ePHRs and patient portals among those managing MCC.

Objective: The aim was to determine the associations between number of chronic conditions and sociodemographic characteristics and usage of ePHRs, and to assess how the public's use of ePHRs varies across subpopulations, including those with MCC.

Methods: This study used data collected from the 2014 Health Information National Trends Survey (HINTS), and assessed differences in use of ePHRs between those with and without MCC (N=3497) using multiple logistic regression techniques. Variables associated with health care systems (insurance status, having a regular provider) and patient-reported self-efficacy were included in the statistical models.

Results: Those with MCC (n=1555) had significantly higher odds of accessing their records three or more times in the past year compared to those reporting no chronic conditions (n=1050; OR 2.46, 95% CI 1.37-4.45), but the overall percentage of those with MCC using ePHRs remained low (371 of 1529 item respondents, 25.63% weighted). No difference in odds of accessing their records was found between those reporting one chronic condition (n=892) and those reporting none (n=1050; OR 1.02, 95% CI 0.66-1.58). Significant differences in odds of accessing ePHRs were seen between income and age groups (P<.001 and P=.05, respectively), and by whether respondents had a regular provider (P=.03).

Conclusions: We conclude that ePHRs provide a unique opportunity to enhance MCC patient self-management, but additional effort is needed to ensure that these patients are able to access their ePHRs. An increase in availability of patient access to their ePHRs may provide an opportunity to increase patient engagement and support self-management for all patients and especially those with MCC.
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http://dx.doi.org/10.2196/jmir.7417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5473948PMC
June 2017

A Nonresponse Bias Analysis of the Health Information National Trends Survey (HINTS).

J Health Commun 2017 07 30;22(7):545-553. Epub 2017 May 30.

b Behavioral Research Program, Division of Cancer Control and Population Sciences , National Cancer Institute, National Institutes of Health , Bethesda , Maryland , USA.

We conducted a nonresponse bias analysis of the Health Information National Trends Survey (HINTS) 4, Cycles 1 and 3, collected in 2011 and 2013, respectively, using three analysis methods: comparison of response rates for subgroups, comparison of estimates with weighting adjustments and external benchmarks, and level-of-effort analysis. Areas with higher concentrations of low socioeconomic status, higher concentrations of young households, and higher concentrations of minority and Hispanic populations had lower response rates. Estimates of health information seeking behavior were higher in HINTS compared to the National Health Interview Survey (NHIS). The HINTS estimate of doctors always explaining things in a way that the patient understands was not significantly different from the same estimate from the Medical Expenditure Panel Survey (MEPS); however, the HINTS estimate of health professionals always spending enough time with the patient was significantly lower than the same estimate from MEPS. A level-of-effort analysis found that those who respond later in the survey field period were less likely to have looked for information about health in the past 12 months, but found only small differences between early and late respondents for the majority of estimates examined. There is some evidence that estimates from HINTS could be biased toward finding higher levels of health information seeking.
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http://dx.doi.org/10.1080/10810730.2017.1324539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114127PMC
July 2017

Planning and Executing the Neurosurgery Boot Camp: The Bolivia Experience.

World Neurosurg 2017 Aug 17;104:407-410. Epub 2017 May 17.

Solidarity Bridge, Evanston, Illinois, USA; Rosalind Franklin Medical School, Rush University Medical Center, Chicago, Illinois, USA.

Background: The neurosurgical boot camp has been fully incorporated into U.S. postgraduate education. This is the first implementation of the neurosurgical boot in a developing country. To advance neurosurgical education, we developed a similar boot camp program, in collaboration with Bolivian neurosurgeons, to determine its feasibility and effectiveness in an international setting.

Methods: In a collective effort, the Bolivian Society for Neurosurgery, Foundation for International Education in Neurological Surgery, Solidarity Bridge, and University of Massachusetts organized and executed the first South American neurosurgical boot camp in Bolivia in 2015. Both U.S. and Bolivian faculty led didactic lectures followed by a practicum day using mannequins and simulators. South American residents and faculty were surveyed after the course to determine levels of enthusiasm and their perceived improvement in fund of knowledge and course effectiveness.

Results: Twenty-four neurosurgery residents from 5 South American countries participated. Average survey scores ranged between 4.2 and 4.9 out of 5. Five Bolivian neurosurgeons completed the survey with average scores of 4.5-5. This event allowed for Bolivian leaders in the field to unify around education, resulting in the formation of an institute to continue similar initiatives. Total cost was estimated at $40 000 USD; however, significant faculty, industry, and donor support helped offset this amount.

Conclusion: The first South American neurosurgical boot camp had significant value and was well received in Bolivia. This humanitarian model provides a sustainable solution to education needs and should be expanded to other regions as a means for standardizing the core competencies in neurosurgery.
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http://dx.doi.org/10.1016/j.wneu.2017.05.046DOI Listing
August 2017

Development of a Unifying Target and Consensus Indicators for Global Surgical Systems Strengthening: Proposed by the Global Alliance for Surgery, Obstetric, Trauma, and Anaesthesia Care (The G4 Alliance).

World J Surg 2017 10;41(10):2426-2434

The College of Surgeons of East, Central and Southern Africa, Arusha, Tanzania.

After decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced-based argument for the fundamental role of surgery and anaesthesia within cost-effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world.
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http://dx.doi.org/10.1007/s00268-017-4028-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596034PMC
October 2017

Public use of electronic personal health information: Measuring progress of the Healthy People 2020 Objectives.

Health Policy Technol 2017 Mar 20;6(1):33-39. Epub 2016 Aug 20.

Department of Psychiatry, Brigham and Women's Hospital, Boston, MA.

Use of the internet for seeking and managing health information in the U.S., Europe, and emerging and developing nations is growing. Recent global trends indicate more interactive uses of the internet including online communication with providers. In the U.S., The Healthy People 2020 (HP2020) initiative was created by the Department of Health and Human Services to provide 10-year goals for improving the health of American citizens. Two goals of HP2020 were to increase the proportion of individuals who use the Internet to keep track of their personal health information (PHI) online and to increase the proportion of individuals who use the internet to communicate with their healthcare provider. In the present study, we use data from the seven administrations of the Health Information National Trends Survey (HINTS) to assess progress towards these goals. These data were analyzed using descriptive, bivariate, and logistic regression analytic techniques. Results of this study suggested that the HP2020 target of having 15.7% of individuals manage their PHI online by 2020 has already been exceeded (28.1%); similarly, the goal for proportion of individuals communicating with their provider using the internet (15.0%) was exceeded by 2014 (29.7%). While progress towards these goals was positive in all sociodemographic groups for both goals, differences in the rate of progress were seen by gender, race/ethnicity, income, and education, but not by age group. The rapidly increasing proportion of individuals globally who use the internet to manage their health information provides unique opportunities for patient-centered health information technology interventions.
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http://dx.doi.org/10.1016/j.hlpt.2016.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415302PMC
March 2017

Assessing nanomaterial exposures in aquatic ecotoxicological testing: Framework and case studies based on dispersion and dissolution.

Nanotoxicology 2017 May 2;11(4):546-557. Epub 2017 May 2.

c U.S. Army Engineer Research and Development Center, Geotechnical and Structures Laboratory , Vicksburg , MS , USA.

The unique behavior of engineered nanomaterials (ENM) in aqueous media and dynamic changes in particle settling, agglomeration and dissolution rates is a challenge to the consistency, reliability and interpretation of standard aquatic hazard bioassay results. While the toxicological endpoints (e.g., survival, growth, reproduction, etc.) in ecotoxicity bioassays are largely applicable to ENMs, the standard methods as written for dissolved substances are confounded by the dynamic settling, agglomeration and dissolution of particulate ENMs during the bioassay. A testing framework was designed to serve as a starting point to identify approaches for the consistent conduct of aquatic hazard tests that account for the behavior of ENMs in test media and suitable data collection to support representative exposure metrology. The framework was demonstrated by conducting three case studies testing ENMs with functionally distinct characteristics and behaviors. Pretests with a temporal sampling of particle concentration, agglomeration and dissolution were conducted on each ENM in test media. Results indicated that a silver nanoparticle (AgNP) powder was not dispersible, a nano-TiO powder was dispersible but unstable, and a polyvinylpyrrolidinone-coated AgNP was relatively stable in test media. Based on these functional results, Ceriodaphnia dubia bioassays were conducted to compare different exposure summary methods (nominal, arithmetic average, geometric average, time-weighted average) for calculating and expressing toxicity endpoints. Results indicated that while arithmetic means were effective for expressing the toxicity of more stable materials, time-weighted averaged concentrations were appropriate for the unstable nano-TiO.
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http://dx.doi.org/10.1080/17435390.2017.1317863DOI Listing
May 2017

What is the difference in concussion management in children as compared with adults? A systematic review.

Br J Sports Med 2017 Jun 28;51(12):949-957. Epub 2017 Apr 28.

Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, Canada.

Aim: To evaluate the evidence regarding the management of sport-related concussion (SRC) in children and adolescents. The eight subquestions included the effects of age on symptoms and outcome, normal and prolonged duration, the role of computerised neuropsychological tests (CNTs), the role of rest, and strategies for return to school and return to sport (RTSp).

Design: Systematic review.

Data Sources: MEDLINE (OVID), Embase (OVID) and PsycInfo (OVID).

Eligibility Criteria For Selecting Studies: Studies were included if they were original research on SRC in children aged 5 years to 18 years, and excluded if they were review articles, or did not focus on childhood SRC.

Results: A total of 5853 articles were identified, and 134 articles met the inclusion criteria. Some articles were common to multiple subquestions. Very few studies examined SRC in young children, aged 5-12 years.

Summary/conclusions: This systematic review recommends that in children: child and adolescent age-specific paradigms should be applied; child-validated symptom rating scales should be used; the widespread routine use of baseline CNT is not recommended; the expected duration of symptoms associated with SRC is less than 4 weeks; prolonged recovery be defined as symptomatic for greater than 4 weeks; a brief period of cognitive and physical rest should be followed with gradual symptom-limited physical and cognitive activity; all schools be encouraged to have a concussion policy and should offer appropriate academic accommodations and support to students recovering from SRC; and children and adolescents should not RTSp until they have successfully returned to school, however early introduction of symptom-limited physical activity is appropriate.

Systematic Review Registration: PROSPERO 2016:CRD42016039184.
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http://dx.doi.org/10.1136/bjsports-2016-097415DOI Listing
June 2017

Anal Neuroendocrine Tumor Masquerading as External Hemorrhoids: A Case Report.

Gastroenterology Res 2017 Feb 21;10(1):56-58. Epub 2017 Feb 21.

Department of Pathology, Saint Francis Medical Center, Trenton, NJ, USA.

Neuroendocrine tumors in gastrointestinal (GI) tract are a rare source of GI malignancy with an estimated incidence of 2.5 - 5 per 100,000 people per year and the prevalence of 35 per 100,000. In the GI tract, they are located in decreasing order of frequency in appendix, ileum, rectum, stomach, and colon. Those found in the anal region represent just 1% of all malignancies of the anal canal. Their clinical presentation can be widely varying, sometimes being found incidentally with metastatic disease and an unknown primary source. We report a case of a 60-year-old male who presented with a 2-week history of intermittent bright red blood per rectum and anal pain. He was found to have a lesion in the perianal area which was subsequently diagnosed has a poorly differentiated large cell type neuroendocrine carcinoma (NEC) with hepatic metastasis.
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http://dx.doi.org/10.14740/gr751wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330695PMC
February 2017

Susceptibility to Food Advertisements and Sugar-Sweetened Beverage Intake in Non-Hispanic Black and Non-Hispanic White Adolescents.

J Community Health 2017 Aug;42(4):748-756

National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850-9761, USA.

Obesity among adolescents in the United States has risen by 16% in the past 30 years. One important contributing factor may be the increased consumption of sugar sweetened beverages (SSBs), which is encouraged by advertisements for unhealthy foods and drinks that are targeted to adolescents. The purpose of this analysis was to determine the association between susceptibility to food and drink advertisements and sugar-sweetened beverage (SSB) consumption in non-Hispanic black (NHB) and non-Hispanic white (NHW) adolescents and to examine if BMI is associated with SSB consumption. Data were obtained from 765 NHB and NHW of ages 14-17 who were surveyed in the Family Life, Activity, Sun, Health, and Eating study sponsored by the National Cancer Institute. Two weighted adjusted logistic regression models were conducted. The first examined the associations of advertisement susceptibility, race, and BMI with SSB consumption. The second examined the associations of race and BMI with advertisement susceptibility. Adolescents with high advertisement susceptibility were more likely to consume at least one SSB daily (OR 1.73, 95% CI 1.21, 2.47). Additionally, non-Hispanic blacks were more likely to consume at least one SSB daily (OR 1.75, 95% CI 1.08, 2.85) and more likely to be highly susceptible to advertisements (OR 1.72, 95% CI 1.19, 2.48) than non-Hispanic whites. No significant associations were found between BMI and advertising susceptibility or BMI and daily SSB consumption. One approach to addressing the consumption of SSBs may be to reduce advertising that markets unhealthy food and beverages to adolescents and minorities.
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http://dx.doi.org/10.1007/s10900-016-0313-4DOI Listing
August 2017

Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells.

Mol Ther 2017 04 23;25(4):949-961. Epub 2017 Feb 23.

Precision BioSciences, Durham, NC 27701, USA. Electronic address:

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cell therapies have produced significant objective responses in patients with CD19 hematological malignancies, including durable complete responses. Although the majority of clinical trials to date have used autologous patient cells as the starting material to generate CAR T cells, this strategy poses significant manufacturing challenges and, for some patients, may not be feasible because of their advanced disease state or difficulty with manufacturing suitable numbers of CAR T cells. Alternatively, T cells from a healthy donor can be used to produce an allogeneic CAR T therapy, provided the cells are rendered incapable of eliciting graft versus host disease (GvHD). One approach to the production of these cells is gene editing to eliminate expression of the endogenous T cell receptor (TCR). Here we report a streamlined strategy for generating allogeneic CAR T cells by targeting the insertion of a CAR transgene directly into the native TCR locus using an engineered homing endonuclease and an AAV donor template. We demonstrate that anti-CD19 CAR T cells produced in this manner do not express the endogenous TCR, exhibit potent effector functions in vitro, and mediate clearance of CD19 tumors in an in vivo mouse model.
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http://dx.doi.org/10.1016/j.ymthe.2017.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383629PMC
April 2017

Factors associated with deciding between risk-reducing salpingo-oophorectomy and ovarian cancer screening among high-risk women enrolled in GOG-0199: An NRG Oncology/Gynecologic Oncology Group study.

Gynecol Oncol 2017 04 10;145(1):122-129. Epub 2017 Feb 10.

Center for Health Policy Research, University of California, Irvine, Irvine, CA 92697, United States. Electronic address:

Objectives: Women at increased genetic risk of ovarian cancer (OC) are recommended to have risk-reducing salpingo-oophorectomy (RRSO) after completion of reproductive planning. Effective screening has not been established, and novel screening modalities are being evaluated.

Methods: Participants chose either RRSO or a novel OC screening regimen (OCS) as their risk management option, and provided demographic and other data on BRCA mutation status, cancer worry, perceived intervention risks/benefits, perceived cancer risk, and quality-of-life at enrollment. We performed univariate and multivariate analyses to evaluate factors influencing decision between RRSO and OCS.

Results: Of 2287 participants enrolled, 904 (40%) chose RRSO and 1383 (60%) chose OCS. Compared with participants choosing OCS, participants choosing RRSO were older (p<0.0001), more likely to carry deleterious BRCA1/2 mutations (p<0.0001), perceive RRSO as effective, be more concerned about surgical harms and OCS limitations, and report higher perceived OC risk and OC-related worry. OCS participants were more likely to perceive screening as effective, be more concerned about menopausal symptoms, infertility, and loss of femininity, and report better overall quality-of-life. Twenty-four percent of participants believed they would definitely develop OC, and half estimated their lifetime OC risk as >50%, both higher than objective risk estimates.

Conclusions: Cancer worry, BRCA1/2 mutation status, and perceived intervention-related risks and benefits were associated with choosing between RRSO and OCS. Efforts to promote individualized, evidence-based, shared medical decision-making among high-risk women facing management choices should focus on conveying accurate OC risk estimates, clarifying the current understanding of intervention-related benefits and limitations, and addressing OC worry.
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http://dx.doi.org/10.1016/j.ygyno.2017.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359045PMC
April 2017

Cognitive and emotional demands of black humour processing: the role of intelligence, aggressiveness and mood.

Cogn Process 2017 May 18;18(2):159-167. Epub 2017 Jan 18.

Department of Neurology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.

Humour processing is a complex information-processing task that is dependent on cognitive and emotional aspects which presumably influence frame-shifting and conceptual blending, mental operations that underlie humour processing. The aim of the current study was to find distinctive groups of subjects with respect to black humour processing, intellectual capacities, mood disturbance and aggressiveness. A total of 156 adults rated black humour cartoons and conducted measurements of verbal and nonverbal intelligence, mood disturbance and aggressiveness. Cluster analysis yields three groups comprising following properties: (1) moderate black humour preference and moderate comprehension; average nonverbal and verbal intelligence; low mood disturbance and moderate aggressiveness; (2) low black humour preference and moderate comprehension; average nonverbal and verbal intelligence, high mood disturbance and high aggressiveness; and (3) high black humour preference and high comprehension; high nonverbal and verbal intelligence; no mood disturbance and low aggressiveness. Age and gender do not differ significantly, differences in education level can be found. Black humour preference and comprehension are positively associated with higher verbal and nonverbal intelligence as well as higher levels of education. Emotional instability and higher aggressiveness apparently lead to decreased levels of pleasure when dealing with black humour. These results support the hypothesis that humour processing involves cognitive as well as affective components and suggest that these variables influence the execution of frame-shifting and conceptual blending in the course of humour processing.
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http://dx.doi.org/10.1007/s10339-016-0789-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5383683PMC
May 2017

Modeling gene-wise dependencies improves the identification of drug response biomarkers in cancer studies.

Bioinformatics 2017 05;33(9):1362-1369

Computational Biology Program, Oregon Health and Science University, Portland, OR 97239, USA.

Motivation: In recent years, vast advances in biomedical technologies and comprehensive sequencing have revealed the genomic landscape of common forms of human cancer in unprecedented detail. The broad heterogeneity of the disease calls for rapid development of personalized therapies. Translating the readily available genomic data into useful knowledge that can be applied in the clinic remains a challenge. Computational methods are needed to aid these efforts by robustly analyzing genome-scale data from distinct experimental platforms for prioritization of targets and treatments.

Results: We propose a novel, biologically motivated, Bayesian multitask approach, which explicitly models gene-centric dependencies across multiple and distinct genomic platforms. We introduce a gene-wise prior and present a fully Bayesian formulation of a group factor analysis model. In supervised prediction applications, our multitask approach leverages similarities in response profiles of groups of drugs that are more likely to be related to true biological signal, which leads to more robust performance and improved generalization ability. We evaluate the performance of our method on molecularly characterized collections of cell lines profiled against two compound panels, namely the Cancer Cell Line Encyclopedia and the Cancer Therapeutics Response Portal. We demonstrate that accounting for the gene-centric dependencies enables leveraging information from multi-omic input data and improves prediction and feature selection performance. We further demonstrate the applicability of our method in an unsupervised dimensionality reduction application by inferring genes essential to tumorigenesis in the pancreatic ductal adenocarcinoma and lung adenocarcinoma patient cohorts from The Cancer Genome Atlas.

Availability And Implementation: : The code for this work is available at https://github.com/olganikolova/gbgfa.

Contact: : [email protected] or [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btw836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860077PMC
May 2017
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