bluuebunny/crossref_metadata_2025 huggingface dataset:
A phenomenological combustion analysis of a dual-fuel natural-gas diesel engine
Authors: Xu Shuonan , Anderson David , Hoffman Mark , Prucka Robert , Filipi Zoran
Published: March 2016

Energy security concerns and an abundant supply of natural gas in the USA provide the impetus for engine designers to consider alternative gaseous fuels in the existing engines. The dual-fuel natural-gas diesel engine concept is attractive because of the minimal design changes, the ability to preserve a high compression ratio of the baseline diesel, and the lack of range anxiety. However, the increased complexity of a dual-fuel engine poses challenges, including the knock limit at a high load, the combustion instability at a low load, and the transient response of an engine with directly injected diesel fuel and port fuel injection of compressed natural gas upstream of the intake manifold. Predictive simulations of the complete engine system are an invaluable tool for investigations of these conditions and development of dual-fuel control strategies. This paper presents the development of a phenomenological combustion model of a heavy-duty dual-fuel engine, aided by insights from experimental data. Heat release analysis is carried out first, using the cylinder pressure data acquired with both diesel-only and dual-fuel (diesel and natural gas) combustion over a wide operating range. A diesel injection timing correlation based on the injector solenoid valve pulse widths is developed, enabling the diesel fuel start of injection to be detected without extra sensors on the fuel injection cam. The experimental heat release trends are obtained with a hybrid triple-Wiebe function for both diesel-only operation and dual-fuel operation. The ignition delay period of dual-fuel operation is examined and estimated with a predictive correlation using the concept of a pseudo-diesel equivalence ratio. A four-stage combustion mechanism is discussed, and it is shown that a triple-Wiebe function has the ability to represent all stages of dual-fuel combustion. This creates a critical building block for modeling a heavy-duty dual-fuel turbocharged engine system.
Surrogate modeling of a 3D scramjet-powered hypersonic vehicle based on screening method IFFD
Authors: Boyi Chen , Yanbin Liu , Haidong Shen , Yuping Lu
Published: March 2016

The emphasis of this paper lies in the development of an efficient approach to reproduce the behaviors of the scramjet-powered hypersonic system with high fidelity. The modeling of the dual-mode scramjet powered hypersonic vehicle dynamics with shock interaction, Ram-to-Scram transition, and finite rate chemistry reaction is firstly introduced. The structure of surrogate model is identified with the implement of iterative fractional factorial design (IFFD). In order to declare the reliability of the surrogate models, ν-gap metric is applied to distinguish the difference among these surrogate models in terms of closed-loop performance. The results show that the influence of Mach number on the aerodynamics should not be overlooked, and the effect of propulsion system to the aerodynamic pitch moment is dramatic. Further, the partial Kriging model appears to have the closest plants throughout the flight envelope compared with the full Kriging model and polynomials model. Nevertheless, considering the briefness of analytical expression, the polynomials model may be an alternative approach for design-oriented modeling.
A biomechanical model of the wrist joint for patient-specific model guided surgical therapy: Part 2
Authors: Eschweiler Jörg , Stromps Jan-Philipp , Fischer Maximilian , Schick Fabian , Rath Björn , Pallua Norbert , Radermacher Klaus
Published: March 2016

An enhanced musculoskeletal biomechanical model of the wrist joint is presented in this article. The computational model is based on the multi-body simulation software AnyBody. Multi body dynamic musculoskeletal models capable of predicting muscle forces and joint contact pressures simultaneously would be valuable for studying clinical issues related to wrist joint degeneration and restoration. In this study, the simulation model of the wrist joint was used for investigating deeper the biomechanical function of the wrist joint. In representative physiological scenarios, the joint behavior and muscle forces were computed. Furthermore, the load transmission of the proximal wrist joint was investigated. The model was able to calculate the parameters of interest that are not easily obtainable experimentally, such as muscle forces and proximal wrist joint forces. In the case of muscle force investigation, the computational model was able to accurately predict the computational outcome for flexion and extension motion. In the case of force distribution of the proximal wrist joint, the model was able to predict accurately the computational outcome for an axial load of 140 N. The presented model and approach of using a multi-body simulation model are anticipated to have value as a predictive clinical tool including effect of injuries or anatomical variations and initial outcome of surgical procedures for patient-specific planning and custom implant design. Therefore, patient-specific multi-body simulation models are potentially valuable tools for surgeons in pre- and intraoperative planning of implant placement and orientation.
Identification of predicted individual treatment effects in randomized clinical trials
Authors: Lamont Andrea , Lyons Michael D , Jaki Thomas , Stuart Elizabeth , Feaster Daniel J , Tharmaratnam Kukatharmini , Oberski Daniel , Ishwaran Hemant , Wilson Dawn K , Van Horn M Lee
Published: March 2016

In most medical research, treatment effectiveness is assessed using the average treatment effect or some version of subgroup analysis. The practice of individualized or precision medicine, however, requires new approaches that predict how an individual will respond to treatment, rather than relying on aggregate measures of effect. In this study, we present a conceptual framework for estimating individual treatment effects, referred to as predicted individual treatment effects. We first apply the predicted individual treatment effect approach to a randomized controlled trial designed to improve behavioral and physical symptoms. Despite trivial average effects of the intervention, we show substantial heterogeneity in predicted individual treatment response using the predicted individual treatment effect approach. The predicted individual treatment effects can be used to predict individuals for whom the intervention may be most effective (or harmful). Next, we conduct a Monte Carlo simulation study to evaluate the accuracy of predicted individual treatment effects. We compare the performance of two methods used to obtain predictions: multiple imputation and non-parametric random decision trees. Results showed that, on average, both predictive methods produced accurate estimates at the individual level; however, the random decision trees tended to underestimate the predicted individual treatment effect for people at the extreme and showed more variability in predictions across repetitions compared to the imputation approach. Limitations and future directions are discussed.
Evaluating hospital infection control measures for antimicrobial-resistant pathogens using stochastic transmission models: Application to vancomycin-resistant enterococci in intensive care units
Authors: Wei Yinghui , Kypraios Theodore , O’Neill Philip D , Huang Susan S , Rifas-Shiman Sheryl L , Cooper Ben S
Published: March 2016

Nosocomial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) are the cause of significant morbidity and mortality among hospital patients. It is important to be able to assess the efficacy of control measures using data on patient outcomes. In this paper, we describe methods for analysing such data using patient-level stochastic models which seek to describe the underlying unobserved process of transmission. The methods are applied to detailed longitudinal patient-level data on vancomycin-resistant Enterococci from a study in a US hospital with eight intensive care units (ICUs). The data comprise admission and discharge dates, dates and results of screening tests, and dates during which precautionary measures were in place for each patient during the study period. Results include estimates of the efficacy of the control measures, the proportion of unobserved patients colonized with vancomycin-resistant Enterococci, and the proportion of patients colonized on admission.
Correcting for dependent censoring in routine outcome monitoring data by applying the inverse probability censoring weighted estimator
Authors: Willems SJW , Schat A , van Noorden MS , Fiocco M
Published: March 2016

Censored data make survival analysis more complicated because exact event times are not observed. Statistical methodology developed to account for censored observations assumes that patients’ withdrawal from a study is independent of the event of interest. However, in practice, some covariates might be associated to both lifetime and censoring mechanism, inducing dependent censoring. In this case, standard survival techniques, like Kaplan–Meier estimator, give biased results. The inverse probability censoring weighted estimator was developed to correct for bias due to dependent censoring. In this article, we explore the use of inverse probability censoring weighting methodology and describe why it is effective in removing the bias. Since implementing this method is highly time consuming and requires programming and mathematical skills, we propose a user friendly algorithm in R. Applications to a toy example and to a medical data set illustrate how the algorithm works. A simulation study was carried out to investigate the performance of the inverse probability censoring weighted estimators in situations where dependent censoring is present in the data. In the simulation process, different sample sizes, strengths of the censoring model, and percentages of censored individuals were chosen. Results show that in each scenario inverse probability censoring weighting reduces the bias induced in the traditional Kaplan–Meier approach where dependent censoring is ignored.
What Can You Teach With Electronic Dance Music? A Music Teacher’s Guide to EDM
Authors: Halick Mary E.
Published: March 2016

Music teachers, who are working to develop students’ musicianship skills, often focus on exposing students to new styles and genres of music. These initiatives encourage students to analyze, develop opinions, create, and perform music they may not normally hear. The purpose of this article is to introduce music educators to Electronic Dance Music (EDM) as a viable option for inclusion in the music education classroom. This article explores the following questions: What is EDM? and What can you teach with EDM? An EDM track list is also included, containing musical and contextual highlights, as well as suggestions for creating, performing, responding, and connecting with EDM. The suggestions are applicable to a variety of classroom environments as well as both progressive and traditional teaching philosophies.
Using Graphic Symbols to Teach Children With Autism to Enter Into Playgroups
Authors: Johnston Susan S. , Nelson Catherine
Published: March 2016

Children with autism spectrum disorder (ASD) may encounter difficulties in various aspects of play, including successful entrance into playgroups. This article describes the practical and applied use of an empirically validated strategy that uses graphic symbols to teach young children with ASD to request entrance into playgroups.
Early Language Milestones and Specific Language Impairment
Authors: Rudolph Johanna M. , Leonard Laurence B.
Published: March 2016

Delayed appearance of early language milestones can be one of the first signs of a developmental disorder. In this study, we investigated how well late acquisition of language milestones predicted an outcome of specific language impairment (SLI). The sample included 150 children (76 SLI), aged 4 to 7 years old. Milestone information was collected via retrospective parent report in a case-control design. Children who produced first words after 15 months met late word producer (LWP) criteria, and children who produced word combinations after 24 months met late word combiner (LWC) criteria. Accuracy metrics indicated that children identified as LWCs were at significantly increased risk of developing SLI (positive likelihood ratio [LR+] = 8.18, 95% confidence interval [CI] = [3.43, 19.53]), whereas children identified as LWPs were not (LR+ = 2.50, 95% CI = [0.95, 6.75]). Notably, a sizable proportion of children with SLI met neither LWP nor LWC criteria. Further analyses indicated that consideration of genetic and environmental risk factors may play an important role in early identification. Our results suggest that delayed milestone achievement is associated with SLI, but that the type of delay matters when making clinical decisions.
Family Quality of Life for Families in Early Intervention in Spain
Authors: Mas Joana M. , Baqués Natasha , Balcells-Balcells Anna , Dalmau Mariona , Giné Climent , Gràcia Marta , Vilaseca Rosa
Published: March 2016

Early intervention (EI) has been shown to be an essential resource for meeting the needs and priorities of children with intellectual and developmental disability and their families. The objective of this study was to examine (a) the perceived quality of life of families attending EI centers in Spain and (b) its relationship with characteristics of the children and their families. The Family Quality of Life Scale was administered to a sample of 281 families with children aged 0 to 6 years attending an EI center. To determine the relationship between family quality of life (FQoL) and the family and children’s characteristics, Student’s t test and one-way ANOVA were performed. Likewise, effect size was measured in those groups. The results show that the emotional well-being of families was high, although they were concerned about health and financial well-being. The perceived FQoL varies depending on income, family type, and severity of the child’s disability. Implications for professional practice in EI centers are presented.
Digital Disruption and the Future of Leadership
Authors: Bolden Richard , O’Regan Nicholas
Published: March 2016

Unprecedented changes in the nature and prevalence of digital technology have significant implications for leadership theory, practice, and development that, as yet, remain largely unexplored in mainstream academic literature. This article features an interview with Rick Haythornthwaite, Chairman of global businesses including Centrica and MasterCard, where he reflects on the ways in which digital disruption is impacting upon the nature of leadership and strategic practice. It is accompanied by a commentary that highlights the importance of factors such as context, trust, ethics, and purpose in a fast moving corporate world.
Psychometric Properties of a Structured Diagnostic Interview for DSM-5 Anxiety, Mood, and Obsessive-Compulsive and Related Disorders
Authors: Tolin David F. , Gilliam Christina , Wootton Bethany M. , Bowe William , Bragdon Laura B. , Davis Elizabeth , Hannan Scott E. , Steinman Shari A. , Worden Blaise , Hallion Lauren S.
Published: March 2016

Three hundred sixty-two adult patients were administered the Diagnostic Interview for Anxiety, Mood, and OCD and Related Neuropsychiatric Disorders (DIAMOND). Of these, 121 provided interrater reliability data, and 115 provided test–retest reliability data. Participants also completed a battery of self-report measures that assess symptoms of anxiety, mood, and obsessive-compulsive and related disorders. Interrater reliability of DIAMOND anxiety, mood, and obsessive-compulsive and related diagnoses ranged from very good to excellent. Test–retest reliability of DIAMOND diagnoses ranged from good to excellent. Convergent validity was established by significant between-group comparisons on applicable self-report measures for nearly all diagnoses. The results of the present study indicate that the DIAMOND is a promising semistructured diagnostic interview for DSM-5 disorders.
Systematic Review and Patient-Level Meta-analysis of the Streamliner Multilayer Flow Modulator in the Management of Complex Thoracoabdominal Aortic Pathology
Authors: Hynes Niamh , Sultan Sherif , Elhelali Ala , Diethrich Edward B. , Kavanagh Edel P. , Sultan Mohamed , Stefanov Florian , Delassus Patrick , Morris Liam
Published: March 2016

Purpose:

To examine the safety and short-term efficacy of the Streamliner Multilayer Flow Modulator (SMFM) in the management of patients with complex thoracoabdominal aortic pathology who are unfit for alternative interventions.

Methods:

Biomedical databases were systematically searched for articles published between 2008 and 2015 on the SMFM. A patient-level meta-analysis was used to evaluate aneurysm-related survival. Secondary outcomes were all-cause survival, stroke, spinal cord ischemia, renal impairment, and branch vessel patency. Other considerations were the impact of compliance with the instructions for use (IFU) on clinical outcome. Mean values and Kaplan-Meier estimates are presented with the 95% confidence interval (CI).

Results:

Fifteen articles (3 multicenter cohort studies, 3 observational cohort studies, and 9 case reports) were included, presenting 171 patients (mean age 68.8±12.3 years; 139 men). The mean aneurysm diameter was 6.7±1.6 cm (95% CI 6.4 to 6.9 cm). Technical success reported in 15 studies was 77.2%. Aneurysm-related survival at 1 year was 78.7% (95% CI 71.7% to 84.4%). One-year all-cause survival was 53.7% (95% CI 46.0% to 61.3%). There were no reported cases of spinal cord ischemia, renal insult, or stroke.

Conclusion:

The SMFM can be safely utilized in some patients with complex thoracoabdominal pathologies provided operators adhere to the IFU. The SMFM is a novel technology with no long-term published data on its sustained effectiveness and a lack of comparative studies. Randomized clinical trials, registries, and continued assessment are essential before this flow-modulating technology can be widely disseminated.
Examining the Classification Accuracy of a Vocabulary Screening Measure With Preschool Children
Authors: Marcotte Amanda M. , Clemens Nathan H. , Parker Christopher , Whitcomb Sara A.
Published: March 2016

This study investigated the classification accuracy of the Dynamic Indicators of Vocabulary Skills (DIVS) as a preschool vocabulary screening measure. With a sample of 240 preschoolers, fall and winter DIVS scores were used to predict year-end vocabulary risk using the 25th percentile on the Peabody Picture Vocabulary Test–Third Edition (PPVT-III) to denote risk status. Results indicated that DIVS Picture Naming Fluency (PNF) and Reverse Definition Fluency (RDF) demonstrated very good accuracy in classifying students according to year-end vocabulary risk status. The DIVS measures also demonstrated stronger accuracy than demographic characteristics known to be indicators of vocabulary difficulties (socioeconomic status, English learner [EL] status, and sex). Combining PNF and RDF did not result in sufficient improvement in accuracy to justify administering both measures as opposed to just one. Further examination of predictive probability values revealed the potential for DIVS measures to improve the precision of vocabulary risk identification over considering EL status alone. Overall, results supported the use of the DIVS as a brief and inexpensive tool for preschool vocabulary screening.
A Newly Designed Enterocutaneous Esophageal Fistula Model in the Pig
Authors: Rahmi Gabriel , Perretta Silvana , Pidial Laetitia , Vanbiervliet Geoffroy , Halvax Peter , Legner Andras , Lindner Veronique , Barthet Marc , Dallemagne Bernard , Cellier Christophe , Clément Olivier
Published: March 2016

Background. Fistulas after esophagectomy are a significant cause of morbidity and mortality. Several endoscopic treatments have been attempted, with varying success. An experimental model that could validate new approaches such as cellular therapies is highly desirable. The aim of this study was to create a chronic esophageal enterocutaneous fistula model in order to study future experimental treatment options. Methods. Eight pigs (six 35-kg young German and two 50-kg adult Yucatan pigs) were used. Through a left and right cervicotomy, under endoscopic view, 1 (group A, n = 6) or 2 (group B, n = 7) plastic catheters were introduced into the esophagus 30 cm from the dental arches bilaterally and left in place for 1 month. Radiologic and endoscopic fistula tract evaluations were performed at postoperative day (POD; 30) and at sacrifice (POD 45). Results. Three fistulas were excluded from the study because of early (POD 5) dislodgment of the catheter, with complete fistula closure. At catheter removal (POD 30), the external orifice was larger in group B (5.2 ± 1.1 mm vs 2.6 ± 0.4 mm) with more severe inflammation (72% vs 33%). At POD 45, the external orifice was closed in all fistulas in group A and in 1/7 in group B. At necropsy, the fistula tract was still present in all animals. Yucatan pigs showed more complex tracts, with a high level of necrosis and substantial fibrotic infiltration. Conclusions. In this article, we show a reproducible, safe, and effective technique to create an esophagocutaneous fistula model in a large experimental animal.
Resilience to Major Life Stressors Is Not as Common as Thought
Authors: Infurna Frank J. , Luthar Suniya S.
Published: March 2016

We attempted to replicate findings that “most people are resilient” following three events: spousal loss, divorce, and unemployment. We applied growth mixture models to the same longitudinal data set that has previously been used to assert that resilience is ubiquitous. When using identical model specifications, as in prior studies, we found that resilient trajectories were most common, but the number of trajectories identified was different. When we relaxed two assumptions used in prior studies—that (a) all classes have similar variability in levels of postadversity adjustment and (b) there is no variability in changes within classes—we found that a resilience class was least common. Methodologically, our results show how findings on trajectories of change following major life stressors can vary substantially, depending on statistical model specifications. Conceptually, the results underscore the errors inherent in any categorical statements about “rates of resilience” among individuals confronted with major life stressors. Pragmatically, they underscore the dangers in recommending against prophylactic interventions (on the basis of one method of analyzing longitudinal data) for individuals who have experienced major life stressors.
Social Identities in a Globalized World
Authors: Rosenmann Amir , Reese Gerhard , Cameron James E.
Published: March 2016

Globalization—the increasing interconnectedness of societies, economies, and cultures—is a defining feature of contemporary social life. Paradoxically, it underlies both the dynamics of global crises (e.g., rising inequality, climate change) and the possibilities for ameliorating them. In this review, we introduce globalization as a multifaceted process and elaborate its psychological effects with respect to identity, culture, and collective action. Using a social identity approach, we discuss three foci of identification: local culture, globalized Western culture, and humanity in its entirety. Each source of identification is analyzed in terms of its psychological meaning and position vis-à-vis the global power structure. Globalized Western culture forms the basis for an exclusive globalized identity, which privileges only some cultures and ways of life. We conceptualize reactions to its core values in terms of cultural identification and rejection and acceptance of, or opposition to, its global social order. Opposition to this inequitable global order is central to inclusive globalized identities (e.g., identification with humanity). These identities may encourage globally minded collective action, even as more research is needed to address their potential caveats. We consider possibilities for social change and action and conclude that a focused application of psychological science to the study of these issues is overdue.
A Comment on Eerland et al. (2016)
Authors: Hart William
Published: March 2016

People imagine criminal behavior in greater detail and ascribe more blame to criminals when a description of a crime is written using the imperfective verb aspect (Hart & Albarracín, 2011, Experiment 3). An initiative to reproduce these findings conducted by Eerland et al. (2016) yielded a lack of replication. Eerland et al. have suggested that the original effect was likely driven by a Type I error produced by methodological aspects of the experiment, including low sample size. Recent conceptual replications of Hart and Albarracín’s effect (Sherrill, Eerland, Zwaan, & Magliano, 2015), however, might imply the effect could be contingent on sample characteristics.
A Foresight Overarching Method
Authors: Goux-Baudiment Fabienne
Published: March 2016

Few disciplines are as vast and diverse as that of foresight. But diversity can lead to fragmentation; to strengthen it as an asset, it is necessary that the fundamentals of its uniqueness are firmly established. Roots for this appear within several factors of oneness embedded in foresight methodological apparatus: first of them, the global toolbox that shows the transition from a research of certainty to anticipation of uncertainty and from very simple tools sketching the reality to a more subtle approach of complexity; second, are the reading grids, namely, here “foresight lens,” that generate these tools and include the worldview, the capacity for discernment, and the creation of such foresight lenses; and finally, and still upstream of paradigms, the different types of knowledge required for the practice of foresight: dynamic, systemic, epistemic, and diagnostic. Built upon these three factors, a meta-method of foresight emerges, transverse to all other methods, inclusive and enriched—not dissolved—by diversity.
The Hidden Curriculum of Futures Studies
Authors: Bussey Marcus
Published: March 2016

Communicating Futures Studies to graduates steeped in specialized disciplinary domains calls for a well-structured series of thought interventions. To achieve this considerable reflexivity is called for on the teacher’s part. This article looks at futures pedagogy and my personal “hidden curriculum.” These reflections hinge on the teaching of a course titled Business and Media Futures. The skeleton of the course is presented, and an outline of the deeper learning processes is offered as a Causal Layered Pedagogy that incorporates the notion of the five Futures Senses.
Prevalence of Beers Criteria Medications Among Elderly Patients in a Military Hospital
Authors: Osei Edward K. , Berry-Cabán Cristóbal S. , Haley Chelsey L. , Rhodes-Pope Heather
Published: March 2016

Objective: This study aims to examine potentially inappropriate medication (PIM) prevalence and factors that affect the use of PIMs in a military treatment facility. Method: Admission and discharge medication lists of 60 patients aged ≥65 years were retrospectively reviewed by a clinical pharmacist and a member of the study team for the presence of PIM using the 2012 Beers Criteria. Patients included were those discharged between December 2012 and September 2013 from the Womack Army Medical Center, Internal Medicine unit. Results: Among the 60 patients evaluated, 44 (73%) were on at least one PIM at admission, whereas the prevalence of PIM at discharge (30 patients) was 50% ( p < .001). The top three classes of PIM at admission were antihistamines (11, 15.3%), nonsteroidal anti-inflammatory drugs (10, 13.9%), and benzodiazepines (6, 8.3%). Patients on >10 medications at admission (37, 62%) were 4 times more likely to have a PIM ( p < .001). Conclusion: Data showed a high and a previously unknown PIM prevalence among older adults in a U.S. military treatment facility.
Splenic marginal zone lymphoma: from genetics to management
Authors: Arcaini Luca , Rossi Davide , Paulli Marco
Published: March 2016

Splenic marginal zone lymphoma (SMZL) is a rare B-cell malignancy involving the spleen, bone marrow, and frequently the blood. SMZL lymphomagenesis involves antigen and/or superantigen stimulation and molecular deregulation of genes (NOTCH2 and KLF2) involved in the physiological differentiation of spleen marginal zone B cells. Diagnosis requires either spleen histology or, alternatively, the documentation of a typical cell morphology and immunophenotype on blood cells coupled with the detection of intrasinusoidal infiltration by CD20+ cells in the bone marrow. Among B-cell tumors, deletion of 7q and NOTCH2 mutations are almost specific lesions of SMZL, thus representing promising diagnostic biomarkers of this lymphoma. Although the majority of SMZLs show an indolent course with a median survival of approximately 10 years, nearly 30% of patients experience a poor outcome. No randomized trials are reported for SMZL, and few prospective trials are available. A watch-and-wait approach is advisable for asymptomatic patients. Treatment options for symptomatic patients ranges from splenectomy to rituximab alone or combined with chemotherapy. In some geographic areas, a subset of patients with SMZL associates with hepatitis C virus infection, prompting virus eradication as an effective lymphoma treatment. It would be worthwhile to explore deregulated cellular programs of SMZL as therapeutic targets in the future; improved clinical and biological prognostication will be essential for identifying patients who may benefit from novel approaches.
Optimizing therapy for nodal marginal zone lymphoma
Authors: Thieblemont Catherine , Molina Thierry , Davi Frédéric
Published: March 2016

Nodal marginal zone lymphoma (NMZL) is a rare form of indolent small B-cell lymphoma which has only been clearly identified in the last 2 decades and which to date remains incurable. Progress in therapeutic management has been slow, largely due to the very small number of patients treated and the heterogeneity of treatments administered; thus, standard-of-care treatment is currently nonspecific for this lymphoma entity. In this review, treatments routinely used to manage adult NMZL patients are presented, principally based on immunochemotherapy (when treatment is needed). Biological research behind the key axes of agents currently under development is described; development of novel agents is heavily based on data from gene profiling and genome-wide sequencing research, uncovering a number of critical deregulated pathways specific to NMZL tumors. These include B-cell receptor, JAK/STAT, NF-κB, NOTCH, and Toll-like receptor signaling pathways, as well as intracellular processes such as the cell cycle, chromatin remodeling, and transcriptional regulation in terms of epigenetic modifiers, histones, or transcriptional co-repressors, along with immune escape via T-cell–mediated tumor surveillance. These pathways are examined in detail and a projection of how the field may evolve in the near future for an efficient personalized treatment approach for NMZL patients is presented.
Comparison of module detection algorithms in protein networks and investigation of the biological meaning of predicted modules
Authors: Tripathi Shailesh , Moutari Salissou , Dehmer Matthias , Emmert-Streib Frank
Published: March 2016

Background

It is generally acknowledged that a functional understanding of a biological system can only be obtained by an understanding of the collective of molecular interactions in form of biological networks. Protein networks are one particular network type of special importance, because proteins form the functional base units of every biological cell. On a mesoscopic level of protein networks, modules are of significant importance because these building blocks may be the next elementary functional level above individual proteins allowing to gain insight into fundamental organizational principles of biological cells.

Results

In this paper, we provide a comparative analysis of five popular and four novel module detection algorithms. We study these module prediction methods for simulated benchmark networks as well as 10 biological protein interaction networks (PINs). A particular focus of our analysis is placed on the biological meaning of the predicted modules by utilizing the Gene Ontology (GO) database as gold standard for the definition of biological processes. Furthermore, we investigate the robustness of the results by perturbing the PINs simulating in this way our incomplete knowledge of protein networks.

Conclusions

Overall, our study reveals that there is a large heterogeneity among the different module prediction algorithms if one zooms-in the biological level of biological processes in the form of GO terms and all methods are severely affected by a slight perturbation of the networks. However, we also find pathways that are enriched in multiple modules, which could provide important information about the hierarchical organization of the system.
The role of neutrophils in immune dysfunction during severe inflammation
Authors: Leliefeld Pieter H. C. , Wessels Catharina M. , Leenen Luke P. H. , Koenderman Leo , Pillay Janesh
Published: March 2016

Critically ill post-surgical, post-trauma and/or septic patients are characterised by severe inflammation. This immune response consists of both a pro- and an anti-inflammatory component. The pro-inflammatory component contributes to (multiple) organ failure whereas occurrence of immune paralysis predisposes to infections. Strikingly, infectious complications arise in these patients despite the presence of a clear neutrophilia. We propose that dysfunction of neutrophils potentially increases the susceptibility to infections or can result in the inability to clear existing infections. Under homeostatic conditions these effector cells of the innate immune system circulate in a quiescent state and serve as the first line of defence against invading pathogens. In severe inflammation, however, neutrophils are rapidly activated, which affects their functional capacities, such as chemotaxis, phagocytosis, intra-cellular killing, NETosis, and their capacity to modulate adaptive immunity. This review provides an overview of the current understanding of neutrophil dysfunction in severe inflammation. We will discuss the possible mechanisms of downregulation of anti-microbial function, suppression of adaptive immunity by neutrophils and the contribution of neutrophil subsets to immune paralysis.
Intraspinal bone-marrow cell therapy at pre- and symptomatic phases in a mouse model of amyotrophic lateral sclerosis
Authors: Gubert Fernanda , Decotelli Ana B. , Bonacossa-Pereira Igor , Figueiredo Fernanda R. , Zaverucha-do-Valle Camila , Tovar-Moll Fernanda , Hoffmann Luísa , Urmenyi Turan P. , Santiago Marcelo F. , Mendez-Otero Rosalia
Published: March 2016

Background

Amyotrophic lateral sclerosis (ALS) is a progressive neurological disease that selectively affects the motor neurons. The details of the mechanisms of selective motor-neuron death remain unknown and no effective therapy has been developed. We investigated the therapy with bone-marrow mononuclear cells (BMMC) in a mouse model of ALS (SOD1G93A mice).

Methods

We injected 106 BMMC into the lumbar portion of the spinal cord of SOD1G93A mice in presymptomatic (9 weeks old) and symptomatic (14 weeks old) phases. In each condition, we analyzed the progression of disease and the lifespan of the animals.

Results

We observed a mild transitory delay in the disease progression in the animals injected with BMMC in the presymptomatic phase. However, we observed no increase in the lifespan. When we injected BMMC in the symptomatic phase, we observed no difference in the animals’ lifespan or in the disease progression. Immunohistochemistry for NeuN showed a decrease in the number of motor neurons during the course of the disease, and this decrease was not affected by either treatment. Using different strategies to track the BMMC, we noted that few cells remained in the spinal cord after transplantation. This observation could explain why the BMMC therapy had only a transitory effect.

Conclusion

This is the first report of intraspinal BMMC therapy in a mouse model of ALS. We conclude this cellular therapy has only a mild transitory effect when performed in the presymptomatic phase of the disease.
The complete genome sequence of Eubacterium limosum SA11, a metabolically versatile rumen acetogen
Authors: Kelly William J. , Henderson Gemma , Pacheco Diana M. , Li Dong , Reilly Kerri , Naylor Graham E. , Janssen Peter H. , Attwood Graeme T. , Altermann Eric , Leahy Sinead C.
Published: March 2016

Acetogens are a specialized group of anaerobic bacteria able to produce acetate from CO2 and H2 via the Wood–Ljungdahl pathway. In some gut environments acetogens can compete with methanogens for H2, and as a result rumen acetogens are of interest in the development of microbial approaches for methane mitigation. The acetogen Eubacterium limosum SA11 was isolated from the rumen of a New Zealand sheep and its genome has been sequenced to examine its potential application in methane mitigation strategies, particularly in situations where hydrogenotrophic methanogens are inhibited resulting in increased H2 levels in the rumen. The 4.15 Mb chromosome of SA11 has an average G + C content of 47 %, and encodes 3805 protein-coding genes. There is a single prophage inserted in the chromosome, and several other gene clusters appear to have been acquired by horizontal transfer. These include genes for cell wall glycopolymers, a type VII secretion system, cell surface proteins and chemotaxis. SA11 is able to use a variety of organic substrates in addition to H2/CO2, with acetate and butyrate as the principal fermentation end-products, and genes involved in these metabolic pathways have been identified. An unusual feature is the presence of 39 genes encoding trimethylamine methyltransferase family proteins, more than any other bacterial genome. Overall, SA11 is a metabolically versatile organism, but its ability to grow on such a wide range of substrates suggests it may not be a suitable candidate to take the place of hydrogen-utilizing methanogens in the rumen.
A model-independent finite-difference method for removal of free-surface generated multiples
Authors: Vasmel Marlies , Robertsson Johan O. A. , Amundsen Lasse
Published: March 2016

We have developed a new data-driven method to solve the free-surface-related multiple problem using forward space-time-domain modeling. We build a finite-difference (FD) modeling engine in which the interaction of any desired wavefield with an unknown subsurface (but without the reflecting sea surface on top) can be modeled. This can either be used to predict the desired primary reflections of the subsurface or to (simultaneously) model all orders of free-surface-related multiples. In this method, we use conventional forward-modeling techniques in combination with a novel type of boundary condition. The wave propagation in the known part of the medium (i.e., the homogeneous water layer) is modeled on an FD grid, whereas the wave propagation in the unknown part of the medium (i.e., the subsurface) is predicted using the recorded multicomponent data. The methodology dynamically links these two distinct domains. We demonstrate the exact method and an adapted version that works under realistic conditions on a synthetic data set for different acquisition geometries. A small-scale test on ocean-bottom cable field data shows that the proposed method readily predicted the expected multiple arrivals in the recorded data.
Costs of the police service and mental healthcare pathways experienced by individuals with enduring mental health needs
Authors: Heslin Margaret , Callaghan Lynne , Barrett Barbara , Lea Susan , Eick Susan , Morgan John , Bolt Mark , Thornicroft Graham , Rose Diana , Healey Andrew , Patel Anita
Published: March 2016

Background

Substantial policy, communication and operational gaps exist between mental health services and the police for individuals with enduring mental health needs.

Aims

To map and cost pathways through mental health and police services, and to model the cost impact of implementing key policy recommendations.

Method

Within a case-linkage study, we estimated 1-year individual-level healthcare and policing costs. Using decision modelling, we then estimated the potential impact on costs of three recommended service enhancements: street triage, Mental Health Act assessments for all Section 136 detainees and outreach custody link workers.

Results

Under current care, average 1-year mental health and police costs were £10 812 and £4552 per individual respectively (n = 55). The cost per police incident was £522. Models suggested that each service enhancement would alter per incident costs by between −8% and +6%.

Conclusions

Recommended enhancements to care pathways only marginally increase individual-level costs.
New insights into the endophenotypic status of cognition in bipolar disorder: Genetic modelling study of twins and siblings
Authors: Georgiades Anna , Rijsdijk Fruhling , Kane Fergus , Rebollo-Mesa Irene , Kalidindi Sridevi , Schulze Katja K. , Stahl Daniel , Walshe Muriel , Sahakian Barbara J. , McDonald Colm , Hall Mei-Hua , Murray Robin M. , Kravariti Eugenia
Published: March 2016

Background

Twin studies have lacked statistical power to apply advanced genetic modelling techniques to the search for cognitive endophenotypes for bipolar disorder.

Aims

To quantify the shared genetic variability between bipolar disorder and cognitive measures.

Method

Structural equation modelling was performed on cognitive data collected from 331 twins/siblings of varying genetic relatedness, disease status and concordance for bipolar disorder.

Results

Using a parsimonious AE model, verbal episodic and spatial working memory showed statistically significant genetic correlations with bipolar disorder (rg = |0.23|–|0.27|), which lost statistical significance after covarying for affective symptoms. Using an ACE model, IQ and visual-spatial learning showed statistically significant genetic correlations with bipolar disorder (rg = |0.51|–|1.00|), which remained significant after covarying for affective symptoms.

Conclusions

Verbal episodic and spatial working memory capture a modest fraction of the bipolar diathesis. IQ and visual-spatial learning may tap into genetic substrates of non-affective symptomatology in bipolar disorder.
Pgrmc1/BDNF Signaling Plays a Critical Role in Mediating Glia-Neuron Cross Talk
Authors: Sun Fen , Nguyen Trinh , Jin Xin , Huang Renqi , Chen Zhenglan , Cunningham Rebecca L. , Singh Meharvan , Su Chang
Published: March 2016

Progesterone (P4) exerts robust cytoprotection in brain slice cultures (containing both neurons and glia), yet such protection is not as evident in neuron-enriched cultures, suggesting that glia may play an indispensable role in P4's neuroprotection. We previously reported that a membrane-associated P4 receptor, P4 receptor membrane component 1, mediates P4-induced brain-derived neurotrophic factor (BDNF) release from glia. Here, we sought to determine whether glia are required for P4's neuroprotection and whether glia's roles are mediated, at least partially, via releasing soluble factors to act on neighboring neurons. Our data demonstrate that P4 increased the level of mature BDNF (neuroprotective) while decreasing pro-BDNF (potentially neurotoxic) in the conditioned media (CMs) of cultured C6 astrocytes. We examined the effects of CMs derived from P4-treated astrocytes (P4-CMs) on 2 neuronal models: 1) all-trans retinoid acid-differentiated SH-SY5Y cells and 2) mouse primary hippocampal neurons. P4-CM increased synaptic marker expression and promoted neuronal survival against H2O2. These effects were attenuated by Y1036 (an inhibitor of neurotrophin receptor [tropomysin-related kinase] signaling), as well as tropomysin-related kinase B-IgG (a more specific inhibitor to block BDNF signaling), which pointed to BDNF as the key protective component within P4-CM. These findings suggest that P4 may exert its maximal protection by triggering a glia-neuron cross talk, in which P4 promotes mature BDNF release from glia to enhance synaptogenesis as well as survival of neurons. This recognition of the importance of glia in mediating P4's neuroprotection may also inform the design of effective therapeutic methods for treating diseases wherein neuronal death and/or synaptic deficits are noted.
The Hollywood Affair: Manuel Puig and the Queer Movie Fan
Authors: Betancourt Manuel
Published: March 2016

Given the Argentine writer Manuel Puig's penchant for using and skewering studio Hollywood films and stars in novels such as Betrayed by Rita Hayworth, he has often been understood as partaking in the discourse of camp. This article takes as a jump-off point the contention that camp is an inadequate framework with which to look at Puig's movie fandom precisely because camp usually brackets the very affection for film that is inherent in fandom. It argues instead for understanding Puig as a queer film fan. During almost daily childhood trips to the movies, he was at once seduced and betrayed by Hollywood and its stars. This article argues that Puig's early texts, The Buenos Aires Affair, with its collection of Hollywood epigraphs, and Kiss of the Spider Woman, with its movie-obsessed protagonist, perform the very concept of queer movie fandom. What one sees in Puig's early texts is a desire to re-create the security in the darkened theater he experienced as a child, a security grounded in the very real and material space of the movie house, by imitating the process of film fan spectatorship in his texts' formal and aesthetic construction. Puig as a young queer film fan, whose own sexual desires were awakened by the films he caught in his childhood, is deployed in his novels as someone who not only enjoys watching these films but constantly retrieves those visual memories and manipulates them.
Scientific Basics of Methodology for Developing Innovative Training Package for School
Authors: ������  , Dronov V.
Published: March 2016

Based on the forecasts of changes in the school education system, analyses of evolution of learning and teaching support and requirements of the Federal

State Educational Standard, the paper provides the guidelines of methodology for development of innovative training packages for school as the

pedagogical system. The general requirements and guidelines for development of appropriate training packages are defi ned, and proposals on how to

reorganize the correspondent editorial-and-publishing process are presented.
Legal Status of the Head of the Municipality: Actual Problem of Finding the Optimum
Authors: Irkhin Igor
Published: March 2016

The content and specific legislative amendments in the regulation of the forms of substitution position of head of the municipality in accordance with the provisions of the federal law 03.02.2015 N 8 «On amendments to articles 32 and 33 of the Federal law “On basic guarantees of electoral rights and the right to participate in a referendum of citizens of the Russian Federation” and the Federal law “On general principles of local self-government in the Russian Federation”» are analyzed in this article. Author analyzed the problems and assessed, evaluated and formulated possible trends of the realization of the institution of city-manager replacement as head of the municipality, the person elected representative body of its members and the head of the local administration, the elected head of the municipality. The liability issues of head of the municipality are analyzed, the relevance of the regulatory definition of effective measures and quality assessment of performed official functions are given, the grounds and procedure responsibility for the improper operation of a regulation of an adequate mechanism for the application of these instruments as well are presented. In terms of issues of selection of the optimal model form of substitution position of head of the municipality author concluded that constitutional due to the trend of development of municipal democracy hampered by
conflicting decisions of the sectoral legislative regulation.