bluuebunny/crossref_metadata_2025 huggingface dataset:
H3K27 Demethylase JMJD3 Employs the NF-κB and BMP Signaling Pathways to Modulate the Tumor Microenvironment and Promote Melanoma Progression and Metastasis
Authors: Park Woo-Yong , Hong Beom-Jin , Lee Jungsul , Choi Chulhee , Kim Mi-Young
Published: January 2016

Histone methylation is a key epigenetic mark that regulates gene expression. Recently, aberrant histone methylation patterns caused by deregulated histone demethylases have been associated with carcinogenesis. However, the role of histone demethylases, particularly the histone H3 lysine 27 (H3K27) demethylase JMJD3, remains largely uncharacterized in melanoma. Here, we used human melanoma cell lines and a mouse xenograft model to demonstrate a requirement for JMJD3 in melanoma growth and metastasis. Notably, in contrast with previous reports examining T-cell acute lymphoblastic leukemia and hepatoma cells, JMJD3 did not alter the general proliferation rate of melanoma cells in vitro. However, JMJD3 conferred melanoma cells with several malignant features such as enhanced clonogenicity, self-renewal, and transendothelial migration. In addition, JMJD3 enabled melanoma cells not only to create a favorable tumor microenvironment by promoting angiogenesis and macrophage recruitment, but also to activate protumorigenic PI3K signaling upon interaction with stromal components. Mechanistic investigations demonstrated that JMJD3 transcriptionally upregulated several targets of NF-κB and BMP signaling, including stanniocalcin 1 (STC1) and chemokine (C–C motif) ligand 2 (CCL2), which functioned as downstream effectors of JMJD3 in self-renewal and macrophage recruitment, respectively. Furthermore, JMJD3 expression was elevated and positively correlated with that of STC1 and CCL2 in human malignant melanoma. Moreover, we found that BMP4, another JMJD3 target gene, regulated JMJD3 expression via a positive feedback mechanism. Our findings reveal a novel epigenetic mechanism by which JMJD3 promotes melanoma progression and metastasis, and suggest JMJD3 as a potential target for melanoma treatment. Cancer Res; 76(1); 161–70. ©2016 AACR.
Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis
Authors: Maxson Julia E. , Abel Melissa L. , Wang Jinhua , Deng Xianming , Reckel Sina , Luty Samuel B. , Sun Huahang , Gorenstein Julie , Hughes Seamus B. , Bottomly Daniel , Wilmot Beth , McWeeney Shannon K. , Radich Jerald , Hantschel Oliver , Middleton Richard E. , Gray Nathanael S. , Druker Brian J. , Tyner Jeffrey W.
Published: January 2016

The amount of genomic information about leukemia cells currently far exceeds our overall understanding of the precise genetic events that ultimately drive disease development and progression. Effective implementation of personalized medicine will require tools to distinguish actionable genetic alterations within the complex genetic landscape of leukemia. In this study, we performed kinase inhibitor screens to predict functional gene targets in primary specimens from patients with acute myeloid leukemia and chronic myelomonocytic leukemia. Deep sequencing of the same patient specimens identified genetic alterations that were then integrated with the functionally important targets using the HitWalker algorithm to prioritize the mutant genes that most likely explain the observed drug sensitivity patterns. Through this process, we identified tyrosine kinase nonreceptor 2 (TNK2) point mutations that exhibited oncogenic capacity. Importantly, the integration of functional and genomic data using HitWalker allowed for prioritization of rare oncogenic mutations that may have been missed through genomic analysis alone. These mutations were sensitive to the multikinase inhibitor dasatinib, which antagonizes TNK2 kinase activity, as well as novel TNK2 inhibitors, XMD8-87 and XMD16-5, with greater target specificity. We also identified activating truncation mutations in other tumor types that were sensitive to XMD8-87 and XMD16-5, exemplifying the potential utility of these compounds across tumor types dependent on TNK2. Collectively, our findings highlight a more sensitive approach for identifying actionable genomic lesions that may be infrequently mutated or overlooked and provide a new method for the prioritization of candidate genetic mutations. Cancer Res; 76(1); 127–38. ©2015 AACR.
Eva1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NF-κB Signaling Pathway
Authors: Ohtsu Naoki , Nakatani Yuka , Yamashita Daisuke , Ohue Shiro , Ohnishi Takanori , Kondo Toru
Published: January 2016

Glioblastoma (GBM)–initiating cells (GIC) are a tumorigenic subpopulation that are resistant to radio- and chemotherapies and are the source of disease recurrence. Therefore, the identification and characterization of GIC-specific factors is critical toward the generation of effective GBM therapeutics. In this study, we investigated the role of epithelial V-like antigen 1 (Eva1, also known as myelin protein zero-like 2) in stemness and GBM tumorigenesis. Eva1 was prominently expressed in GICs in vitro and in stem cell marker (Sox2, CD15, CD49f)-expressing cells derived from human GBM tissues. Eva1 knockdown in GICs reduced their self-renewal and tumor-forming capabilities, whereas Eva1 overexpression enhanced these properties. Eva1 deficiency was also associated with decreased expression of stemness-related genes, indicating a requirement for Eva1 in maintaining GIC pluripotency. We further demonstrate that Eva1 induced GIC proliferation through the activation of the RelB-dependent noncanonical NF-κB pathway by recruiting TRAF2 to the cytoplasmic tail. Taken together, our findings highlight Eva1 as a novel regulator of GIC function and also provide new mechanistic insight into the role of noncanonical NF-κB activation in GIC, thus offering multiple potential therapeutic targets for preclinical investigation in GBM. Cancer Res; 76(1); 171–81. ©2015 AACR.
IL17A-Mediated Endothelial Breach Promotes Metastasis Formation
Authors: Kulig Paulina , Burkhard Sara , Mikita-Geoffroy Joanna , Croxford Andrew L. , Hövelmeyer Nadine , Gyülvészi Gabor , Gorzelanny Christian , Waisman Ari , Borsig Lubor , Becher Burkhard
Published: January 2016

The role of the IL23/IL17A axis in tumor–immune interactions is a matter of controversy. Although some suggest that IL17A-producing T cells (TH17) can suppress tumor growth, others report that IL17A and IL23 accelerate tumor growth. Here, we systematically assessed the impact of IL17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate mapping revealed that IL17A was secreted within lung metastases predominantly by γδ T cells, whereas TH17 cells were virtually absent. Using different tumor models, we found Il17a−/− mice to consistently develop fewer pulmonary tumor colonies. IL17A specifically increased blood vessel permeability and the expression of E-selectin and VCAM-1 by lung endothelial cells in vivo. In transgenic mice, specific targeting of IL17A to the endothelium increased the number of tumor foci. Moreover, the direct impact of IL17A on lung endothelial cells resulted in impaired endothelial barrier integrity, showing that IL17A promotes the formation of lung metastases through tumor-endothelial transmigration. Cancer Immunol Res; 4(1); 26–32. ©2015 AACR.
Effect of a Heated Breathing Tube on Efficacy, Adherence and Side Effects during Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea
Authors: Galetke Wolfgang , Nothofer Eleonore , Priegnitz Christina , Anduleit Norbert , Randerath Winfried
Published: January 2016

Background: Heated breathing tubes were developed to improve heated humidification in continuous positive airway pressure (CPAP) therapy of patients with obstructive sleep apnea syndrome (OSAS). Objectives: We wanted to investigate the influence of a heated breathing tube on patients' satisfaction with the treatment, the rate of side effects and the adherence to treatment. Methods: Eighty-eight patients with primarily diagnosed OSAS were treated in a randomized, controlled, single-blind trial for 12 months either with a CPAP system plus conventional heated humidifier or with a CPAP system plus heated humidifier and an integrated heated breathing tube. Results: Both systems improved the respiratory disturbances and the quality of sleep in a similar manner. The difference in the overall satisfaction with the treatment (subscale 3 of the visual analogue scale) between the two treatment groups was not statistically significant (mean difference -14.1, 95% CI -28.7 to 0.6; p = 0.059). The rate of side effects and the quality of life did not differ significantly between the two groups. The patients with the heated breathing tube used the treatment on average 1 h longer, but this was not statistically significant (4.96 ± 1.95 vs. 3.90 ± 2.54 h/night; p = 0.06). Conclusions: Controlled heated breathing tube humidification as compared to conventional heated humidification improves neither the adherence to treatment, nor the rate of side effects, nor the quality of life in nonselected OSAS patients.
Abortion and Infant Mortality on the First Day of Life
Authors: Auger Nathalie , Bilodeau-Bertrand Marianne , Sauve Reg
Published: January 2016

Background: Fetal imaging for congenital anomalies increases pregnancy terminations late in gestation. Objectives: We assessed whether late-pregnancy terminations can accidentally result in live births, and how these births impact infant mortality rates over time. Methods: We carried out a population-level analysis of 12,141 infant deaths in Quebec, Canada from 1986 to 2012. We calculated the proportion of infants born alive who died following pregnancy termination. The exposure was pregnancy termination with or without congenital anomaly recorded on death certificates. The main outcome was mortality on the first day of life by the hour. Results: Pregnancy termination was the cause of 19.4 infant deaths per 100,000 in 2000-2012, compared with 1.0 per 100,000 in 1986-1999. Most deaths after termination occurred in the first 3 h of life among infants with anomalies who weighed <500 g. In 2000-2012, infants who died following pregnancy termination led to an excess of 0.2 deaths per 1,000 on the first day of life, i.e. an 8.6% increase in the infant mortality rate (p value = 0.002). Conclusions: Pregnancy termination in mid-gestation carries the risk of accidental live birth. These neonates increasingly affect infant mortality rates. Better recording is needed, including data on the prevention and management of accidental live births after pregnancy termination.
High Frequency of Normal Response during GH Stimulation Tests in Patients with Ectopic Posterior Pituitary Gland: A Source of False-Negative Diagnosis of Pituitary Insufficiency
Authors: Kochi Cristiane , Scuderi Cindy Greicy Bruginski , Barros Lara , Ribeiro Letícia , Amadei Gustavo , Maruichi Marcelo Damaso , da Rocha Antonio José , Longui Carlos Alberto
Published: January 2016

Aims: To report false-negative normal growth hormone (GH) peak response in patients with ectopic posterior pituitary gland (EPP) identified with a simplified magnetic resonance imaging (FAST1-MRI). Methods: We analyzed 75 EPP patients with short stature and reduced growth velocity. Sagittal-T1 imaging (thickness: 2 mm and gap: 0.2 mm) without gadolinium administration was used. A GH peak of ≥5 ng/ml after clonidine or insulin stimulation was considered normal. Results: Normal GH response was observed in 15 of 75 (20%) patients [mean (SDS) peak = 8.2 (4.1) ng/ml]. Age at diagnosis [6.5 (3.0) years vs. 7.8 (4.1) years], gender (10 males/5 females vs. 44 males/16 females), pubertal stage (14 prepubertal/1 pubertal vs. 51 prepubertal/7 pubertal), and target height [-0.4 (0.6) vs. -0.4 (0.9)] were recorded. The perinatal history did not differ between responsive and nonresponsive patients. There was a trend to more frequent multiple hormone deficiency in nonresponsive when compared with responsive patients [3/15 (20%) and 31/60 (51.7%), respectively (p = 0.055)]. Height at diagnosis was lower in nonresponsive patients (p = 0.042). No significant difference in the IGF1 levels (p = 0.598) was observed between the groups. Conclusion: Normal GH values after stimulation tests do not exclude EPP-associated GH deficiency. A simplified fast acquisition sagittal-T1 MRI protocol investigation included at the initial diagnostic approach is able to prevent misdiagnosis of GH deficiency in patients with short stature.
The Prevalence of Chronic Obstructive Pulmonary Disease by the Global Lung Initiative Equations in North-Western Russia
Authors: Andreeva Elena , Pokhaznikova Marina , Lebedev Anatoly , Moiseeva Irina , Kutznetsova Olga , Degryse Jean-Marie
Published: January 2016

Background: The prevalence of chronic obstructive pulmonary disease (COPD) varies in different countries, while the cut-off for airflow obstruction (AO) is still contested. No COPD prevalence data based on the Global Lung Initiative (GLI) 2012 equations are available in Russia. Objectives: This study aims to assess AO prevalence by the GLI lower limit of normal (GLI-LLN) and the fixed cut-off, to identify AO risk factors and to assess the diagnostic value of respiratory symptoms in north-western Russia. Methods: In a north-western Russian population-based sample of 2,974 adults aged 35-70 years, data on socio-demographics, smoking, occupational exposures and respiratory symptoms were collected, and spirometry was performed before and after bronchodilator (BD) administration. Results: The AO prevalence was 6.8% (95% CI 5.8-7.9) based on the fixed and 4.8% (95% CI 3.9-5.7) based on the GLI-LLN cut-off. 22.5% of the participants with post-BD AO had a positive bronchodilator test, and 1% showed a paradoxical BD response. Of the environmental factors studied, only smoking was independently associated with AO (odds ratio 2.47, 95% CI 1.60-3.82). The positive predictive value of respiratory symptoms for AO was 11% based on the fixed and 8% based on the GLI-LLN cut-off. Conclusions: In a sample of adults in north-western Russia, the AO prevalence by the GLI-LLN cut-off was lower than that by the fixed cut-off. The predictive value of respiratory symptoms was low.
Existential Antagonisms: Boundary Work and the Professional Ideology of Turkish Industrial Designers
Authors: Ilhan Ali O. , Er H. Alpay
Published: January 2016

Industrial design (ID) is a fairly young and largely unknown profession in Turkey. Although significant developments have taken place in the field of ID in the past 15 years, the scope of scholarly attempts to analyze the sociological meaning of designing in the Turkish context is extremely limited.

We use boundary work and professional ideology as salient concepts for a sociological understanding the ongoing professionalization process of Turkish industrial designers, who are developing professional identities and striving for recognition in the larger culture. This paper relies on 20 semi-structured interviews conducted with key players (i.e., ideologues) of the Turkish ID scene to analyze these boundary-work processes.

We found that the positive collective identity of Turkish industrial designers is built on a formulation of negative others. These negative others are ideological antagonists that are pushed to the “other” side of the demarcation line. Negative others are especially dominant in the professional ideology of Turkish industrial designers because the perceived threats from these antagonists shape the collective consciousness. However, the construction of these others is an ambivalent process in which they also become ideological “friends.” We also demonstrate that professional ideology plays a pivotal role in producing, reproducing, and legitimizing claims of professionalism.
Maximum Effect for Minimum Means: The Aesthetics of Efficiency
Authors: da Silva Odette , Crilly Nathan , Hekkert Paul
Published: January 2016

The aesthetic judgment of an artifact is usually interpreted as an assessment of the artifact's sensory properties. But an artifact can also be appreciated, and still aesthetically, for the way it fulfills its purpose. Existing design theory does not provide the concepts required for describing this aspect of aesthetic appreciation and so cannot fully explain what people mean when they say a product is beautiful. In this paper, we develop an understanding of the aesthetic judgment based on the principle of maximum effect for minimum means. We explain how a means–effect relationship can be established between a product and its purpose or effect, and how the product and the effect can be perceived to be minimal and maximal. We also explain how the appreciation of this relationship depends on a set of assumed alternatives for both the product or means and the effect. Finally, we provide some directions for future research into design aesthetics.
Design and Thoughtfulness
Authors: Wylant Barry
Published: January 2016

This paper offers an examination of thoughtfulness in design, one that focuses more on the mechanism of thought rather than any new methodological spin. The investigation is contextually nested within a temporal discussion of design activity, which is then used to pinpoint the smallest kernel of thought that can initiate a given design effort. Aspects of design articulation and design intent are used to explore the nature, and qualities of thoughtfulness as the design work evolves. An inherent flexibility of perception and consideration attend this thoughtfulness, allowing designers to arrive at new insights, and critically assess their work as efforts unfold. Such flexibility and criticality are seen to be habitually exercised at a minute scale, almost with every drawing or computer stroke. In this way, the endeavor is at times meandering, but always intense, facilitating an organic growth in the design articulation that ultimately results in a sophisticated design response.
Storm-Scale Data Assimilation and Ensemble Forecasting with the NSSL Experimental Warn-on-Forecast System. Part II: Combined Radar and Satellite Data Experiments
Authors: Jones Thomas A. , Knopfmeier Kent , Wheatley Dustan , Creager Gerald , Minnis Patrick , Palikonda Rabindra
Published: January 2016

This research represents the second part of a two-part series describing the development of a prototype ensemble data assimilation system for the Warn-on-Forecast (WoF) project known as the NSSL Experimental WoF System for ensembles (NEWS-e). Part I describes the NEWS-e design and results from radar reflectivity and radial velocity data assimilation for six severe weather events occurring during 2013 and 2014. Part II describes the impact of assimilating satellite liquid and ice water path (LWP and IWP, respectively) retrievals from the GOES Imager along with the radar observations. Assimilating LWP and IWP observations may improve thermodynamic conditions at the surface over the storm-scale domain through better analysis of cloud coverage in the model compared to radar-only experiments. These improvements sometimes corresponded to an improved analysis of supercell storms leading to better forecasts of low-level vorticity. This positive impact was most evident for events where convection is not ongoing at the beginning of the radar and satellite data assimilation period. For more complex cases containing significant amounts of ongoing convection, only assimilating clear-sky satellite retrievals in place of clear-air reflectivity resulted in spurious regions of light precipitation compared to the radar-only experiments. The analyzed tornadic storms in these experiments are sometimes too weak and quickly diminished in intensity in the forecasts. The lessons learned as part of these experiments should lead to improved iterations of the NEWS-e system, building on the modestly successful results described here.
Family Involvement in Business and Financial Performance: A Panel Data Analysis
Authors: Gill Suveera , Kaur Parmjit
Published: January 2016

Executive Summary

The economic backdrop of most nations remains dominated by family businesses. Family control is common in publicly traded Indian companies. Such controlling families often hold large shareholdings and for the most part have representation at the top management level as well as on the board. Consequently, an overarching question that emerges is whether and how family ownership, management, and governance affect corporate performance.

This article attempts to discern the relationship between family involvement in business (FIB) and financial performance (FP) of companies included in the S&P BSE 500 Index during the period 2006–2010. In addition, an attempt has been made to examine the difference in accounting and market measures of FP for family companies (FCs) vis-à-vis non-family companies (NFCs). A two-way fixed-effects panel model was used to examine the FIB–FP relationship with fixed effects being dummy variables for each year of the sample and dummy variables for each two-digit National Industrial Classification (NIC) code. Finally, to test for the ‘reverse causation’ between FIB and FP, the instrumental-variable—two-stage least-squares (IV-2SLS) regression was applied.

The results confirm that FCs are a predominant form over a number of industries in a large sample, S&P BSE 500 Index. In addition, founding families are often involved in the actual management of the companies. Controlling for company-specific, industry affiliation, and corporate governance variables, the cross-sectional longitudinal analyses show that FIB is associated with superior FP. Furthermore, FP is higher for FCs vis-à-vis NFCs. Based on the market performance measure, FC appear to be better performers with higher outside board representations. On further analysis of the profile of independent directors, it was observed that they had a diverse background and expertise. The impact of firm size and unaffiliated blockholdings on FP was found to be significantly negative. Finally, the estimates from the IV-2SLS were found to be consistent with the preliminary results that FIB is associated with better FP.

This article joins the evolving concurrence on the diversity and heterogeneity of family businesses by differentiating between family-owned, family-managed, and family-governed companies. It distinguishes itself from previous studies on the subject, as it uses different typologies based on the extent of FIB as well as presents multiple theoretical perspectives rather than a mono-theoretical view to empirical findings in the present study. Keeping this distinction in perspective is imperative for family business researchers, practitioners, and policymakers.
Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma
Authors: Magarotto Valeria , Bringhen Sara , Offidani Massimo , Benevolo Giulia , Patriarca Francesca , Mina Roberto , Falcone Antonietta Pia , De Paoli Lorenzo , Pietrantuono Giuseppe , Gentili Silvia , Musolino Caterina , Giuliani Nicola , Bernardini Annalisa , Conticello Concetta , Pulini Stefano , Ciccone Giovannino , Maisnar Vladimír , Ruggeri Marina , Zambello Renato , Guglielmelli Tommasina , Ledda Antonio , Liberati Anna Marina , Montefusco Vittorio , Hajek Roman , Boccadoro Mario , Palumbo Antonio
Published: January 2016

Key Points

Triplet lenalidomide-based regimens did not induce any advantage over doublet lenalidomide-based regimens in elderly myeloma patients.
Diffany: an ontology-driven framework to infer, visualise and analyse differential molecular networks
Authors: Landeghem Sofie Van , Parys Thomas Van , Dubois Marieke , Inzé Dirk , de Peer Yves Van
Published: January 2016

Background

Differential networks have recently been introduced as a powerful way to study the dynamic rewiring capabilities of an interactome in response to changing environmental conditions or stimuli. Currently, such differential networks are generated and visualised using ad hoc methods, and are often limited to the analysis of only one condition-specific response or one interaction type at a time.

Results

In this work, we present a generic, ontology-driven framework to infer, visualise and analyse an arbitrary set of condition-specific responses against one reference network. To this end, we have implemented novel ontology-based algorithms that can process highly heterogeneous networks, accounting for both physical interactions and regulatory associations, symmetric and directed edges, edge weights and negation. We propose this integrative framework as a standardised methodology that allows a unified view on differential networks and promotes comparability between differential network studies. As an illustrative application, we demonstrate its usefulness on a plant abiotic stress study and we experimentally confirmed a predicted regulator.

Availability

Diffany is freely available as open-source java library and Cytoscape plugin from http://bioinformatics.psb.ugent.be/supplementary_data/solan/diffany/.
An efficient genome-wide association test for multivariate phenotypes based on the Fisher combination function
Authors: Yang James J. , Li Jia , Williams L. Keoki , Buu Anne
Published: January 2016

Background

In genome-wide association studies (GWAS) for complex diseases, the association between a SNP and each phenotype is usually weak. Combining multiple related phenotypic traits can increase the power of gene search and thus is a practically important area that requires methodology work. This study provides a comprehensive review of existing methods for conducting GWAS on complex diseases with multiple phenotypes including the multivariate analysis of variance (MANOVA), the principal component analysis (PCA), the generalizing estimating equations (GEE), the trait-based association test involving the extended Simes procedure (TATES), and the classical Fisher combination test. We propose a new method that relaxes the unrealistic independence assumption of the classical Fisher combination test and is computationally efficient. To demonstrate applications of the proposed method, we also present the results of statistical analysis on the Study of Addiction: Genetics and Environment (SAGE) data.

Results

Our simulation study shows that the proposed method has higher power than existing methods while controlling for the type I error rate. The GEE and the classical Fisher combination test, on the other hand, do not control the type I error rate and thus are not recommended. In general, the power of the competing methods decreases as the correlation between phenotypes increases. All the methods tend to have lower power when the multivariate phenotypes come from long tailed distributions. The real data analysis also demonstrates that the proposed method allows us to compare the marginal results with the multivariate results and specify which SNPs are specific to a particular phenotype or contribute to the common construct.

Conclusions

The proposed method outperforms existing methods in most settings and also has great applications in GWAS on complex diseases with multiple phenotypes such as the substance abuse disorders.
Impact of prolonged assisted ventilation on diaphragmatic efficiency: NAVA versus PSV
Authors: Di mussi Rosa , Spadaro Savino , Mirabella Lucia , Volta Carlo Alberto , Serio Gabriella , Staffieri Francesco , Dambrosio Michele , Cinnella Gilda , Bruno Francesco , Grasso Salvatore
Published: January 2016

Background

Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency.

Method

Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours.

Results

In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/μV at baseline to 62 ± 30 ml/μV at 48 hours (p <0.0001) and neuro-mechanical efficiency increased from 1 ± 0.6 to 2.6 ± 1.1 cmH2O/μV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38– 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78– 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04).

Conclusion

After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not.

Trial registration

ClinicalTrials.gov study registration: NCT0247317, 06/11/2015.
Patient outcomes following discharge from secure psychiatric hospitals: Systematic review and meta-analysis
Authors: Fazel Seena , Fimińska Zuzanna , Cocks Christopher , Coid Jeremy
Published: January 2016

Background

Secure hospitals are a high-cost, low-volume service consuming around a fifth of the overall mental health budget in England and Wales.

Aims

A systematic review and meta-analysis of adverse outcomes after discharge along with a comparison with rates in other clinical and forensic groups in order to inform public health and policy.

Method

We searched for primary studies that followed patients discharged from a secure hospital, and reported mortality, readmissions or reconvictions. We determined crude rates for all adverse outcomes.

Results

In total, 35 studies from 10 countries were included, involving 12 056 patients out of which 53% were violent offenders. The crude death rate for all-cause mortality was 1538 per 100 000 person-years (95% CI 1175–1901). For suicide, the crude death rate was 325 per 100 000 person-years (95% CI 235– 415). The readmission rate was 7208 per 100 000 person-years (95% CI 5916–8500). Crude reoffending rates were 4484 per 100 000 person-years (95% CI 3679–5287), with lower rates in more recent studies.

Conclusions

There is some evidence that patients discharged from forensic psychiatric services have lower offending outcomes than many comparative groups. Services could consider improving interventions aimed at reducing premature mortality, particularly suicide, in discharged patients.
FoxO1 Plays an Important Role in Regulating β-Cell Compensation for Insulin Resistance in Male Mice
Authors: Zhang Ting , Kim Dae Hyun , Xiao Xiangwei , Lee Sojin , Gong Zhenwei , Muzumdar Radhika , Calabuig-Navarro Virtu , Yamauchi Jun , Harashima Hideyoshi , Wang Rennian , Bottino Rita , Alvarez-Perez Juan Carlos , Garcia-Ocaña Adolfo , Gittes George , Dong H. Henry
Published: January 2016

β-Cell compensation is an essential mechanism by which β-cells increase insulin secretion for overcoming insulin resistance to maintain euglycemia in obesity. Failure of β-cells to compensate for insulin resistance contributes to insulin insufficiency and overt diabetes. To understand the mechanism of β-cell compensation, we characterized the role of forkhead box O1 (FoxO1) in β-cell compensation in mice under physiological and pathological conditions. FoxO1 is a key transcription factor that serves as a nutrient sensor for integrating insulin signaling to cell metabolism, growth, and proliferation. We showed that FoxO1 improved β-cell compensation via 3 distinct mechanisms by increasing β-cell mass, enhancing β-cell glucose sensing, and augmenting β-cell antioxidative function. These effects accounted for increased glucose-stimulated insulin secretion and enhanced glucose tolerance in β-cell-specific FoxO1-transgenic mice. When fed a high-fat diet, β-cell-specific FoxO1-transgenic mice were protected from developing fat-induced glucose disorder. This effect was attributable to increased β-cell mass and function. Furthermore, we showed that FoxO1 activity was up-regulated in islets, correlating with the induction of physiological β-cell compensation in high-fat-induced obese C57BL/6J mice. These data characterize FoxO1 as a pivotal factor for orchestrating physiological adaptation of β-cell mass and function to overnutrition and obesity.
Speculation
Authors: Bear Laura , Birla Ritu , Puri Stine Simonsen
Published: January 2016

Speculation structures the unprecedented breadth and depth of contemporary global capitalism. We define it as an engagement with uncertainty that aims to materialize potential futures. Studies of economization and financialization have highlighted the production of value through transparent practices of calculation and have focused on the Global North. As an alternative, we use ethnographic and historical genealogical methods to explore predictive practices that are motivated by contingency and aim to make uncertainty productive. India, a celebrated emerging market and dense arena of capitalist promise and failure, provides the foundations for our approach. The speculative practices we focus on challenge the distinction between formal and informal, the licit and illicit, because they fuel rationalized market regimes, as well as worlds of precarity. Our approach reveals the governmentalities, public cultures, and market actions that are characteristic of the present pursuit of value for profit and survival.
The Economy of Anticipation
Authors: Cross Jamie
Published: January 2016

The export processing or free trade zones that have been built since the 1960s across Central America and the Caribbean, north Africa and the Gulf states, and South and Southeast Asia have emerged as uniquely charged objects of anticipation—hope, conviction, and anxiety—about the capitalist future as much as sites of speculative investment in financial futures. This essay sets out to broaden our engagement of the diverse futures invested in these large-scale industrial infrastructure projects by examining the economy of anticipation upon which they are built.
Evolutionarily conserved primary TNF sequences relate to its primitive functions in cell death induction
Authors: Lu Wenshu , Chen Qiongyu , Ying Songmin , Xia Xiaobing , Yu Zhanru , Lui Yuan , Tranter George , Jin Boquan , Song Chaojun , Seymour Leonard W. , Jiang Shisong
Published: January 2016

TNF is a primitive protein that has emerged from more than 550 million years of evolution. Our bioinformatics study of TNF from nine different taxa in vertebrates revealed several conserved regions in the TNF sequence. By screening overlapping peptides derived from human TNF to determine their role in three different TNF-induced processes – apoptosis, necrosis and NF-κB stimulation – we found that TNF conserved regions are mostly related to cell death rather than NF-κB stimulation. Among the most conserved regions, peptides (P)12, P13 and P1213 (comprising P12 and P13) induced apoptosis, whereas P14, P15, P16 and P1516 (comprising P15 and P16) induced necrosis. Cell death induced by these peptides was not through binding to the TNF receptor. P16-induced necrosis was mainly through disruption of the cell membrane, whereas P1213-induced apoptosis involved activation of TRADD followed by formation of complex II. Finally, using a monoclonal antibody and a mutant TNF protein, we show that TNF-induced apoptosis is determined by a conserved linear sequence that corresponds to that within P1213. Our results reveal the determinant sequence that is key to the TNF primitive function of inducing apoptosis.
Multifunctional Abl kinases in health and disease
Authors: Khatri Aaditya , Wang Jun , Pendergast Ann Marie
Published: January 2016

The Abelson tyrosine kinases were initially identified as drivers of leukemia in mice and humans. The Abl family kinases Abl1 and Abl2 regulate diverse cellular processes during development and normal homeostasis, and their functions are subverted during inflammation, cancer and other pathologies. Abl kinases can be activated by multiple stimuli leading to cytoskeletal reorganization required for cell morphogenesis, motility, adhesion and polarity. Depending on the cellular context, Abl kinases regulate cell survival and proliferation. Emerging data support important roles for Abl kinases in pathologies linked to inflammation. Among these are neurodegenerative diseases and inflammatory pathologies. Unexpectedly, Abl kinases have also been identified as important players in mammalian host cells during microbial pathogenesis. Thus, the use of Abl kinase inhibitors might prove to be effective in the treatment of pathologies beyond leukemia and solid tumors. In this Cell Science at a Glance article and in the accompanying poster, we highlight the emerging roles of Abl kinases in the regulation of cellular processes in normal cells and diverse pathologies ranging from cancer to microbial pathogenesis.
The Measure of the Effectiveness of E - Learning by using Academic Scientific Materials which are Available on the Internet : Analytical and Descriptive Study in Al – Mustansiriya University According to (NOURI- NET ) System
Authors: Hassan Haider
Published: January 2016

The study aims to measure the effect of using academic scientific materials on the World Wide Web in education , through the Availability educational materials , and displayed an electronically using software (NOURI- NET ) to evaluate the web-based course in terms of its of use and the acceptance which are used by students the level of benefit, and the study surveyed (70) students in all disciplines at the Al-mustansiriya university during (2010 –2011) by using methods of scale(likert) to collect information about learners  associated with variables of the study.
The result of this study reveals that the students acceptance of the web-based instruction was high and the use of  the web-based materials positively affects the learning skills of the students . however , functional problems were found in terms of using the web –based materials .
The knowledge enabling at the university library: Towards an effective management of competencies in the knowledge society
Authors: Kahlaa Samraa , Chabounia Omar
Published: January 2016

This study aims to deepening the comprehension of the reality of knowledge and its management which necessitates a knowledge about management that takes the individual and the tacit knowledge he possesses as two faces for the valuable currency of superiority taking  university libraries in Batna a model for our study that can be considered as necessary steps to rely on, A great consideration is given to knowledge till has become an important aspect of its practices that is to say Knowledge Management, The maturity of the knowledge working grows when the individual can do what he knows through Enabling knowledge.
Crowdsourcing Research: A Methodology for Investigating State Crime
Authors: Williams Christopher
Published: January 2016

“Crowdsourcing” now gets 10 million hits on Google, and is being applied to research in commercial, media, academic, civil society and state spheres. Although appearing recent and technology-based, there are also relevant but overlooked manual precursors which embody the fundamentals of using large groups for research. This analytical review provides the bases for developing initiatives further, by assessing: What are the strategies, strengths and weaknesses of crowdsourcing research? What are the questions that should be asked when planning a research design? How is crowdsourcing being applied in relation to state crime, and why? What might be the implications for justice systems, and for criminal and international courts?
Employment and Economic Self-Sufficiency:2015 National Goals for Research, Policy, and Practice
Authors: Nord Derek , Barkoff Allison , Butterworth John , Carlson Dawn , Cimera Robert , Fabian Ellen , Grossi Teresa , Hall Allison , Lucus Jonathan , Nye-Lengerman Kelly , Gower Wendy Strobel , Tyree Milton , Von Schrader Sarah , Wohl Allison
Published: January 2016

Employment in general workforce and economic self-sufficiency continue to be the exceptions for people with intellectual and developmental disabilities (IDD), rather than the norm. Research, policy, and practice can and should play a coordinated role in solving this problem. This article summarizes the methods used and the consensus-based national goals identified to guide the direction of the field that were developed by experts in the field. A discussion of the implications of the findings is also provided, including the need for advocacy to advance the goals.
Kilka uwag o nieodnotowanych w słownikach współczesnej polszczyzny formacjach feminatywnych
Authors: Piotrowicz Anna , Witaszek-Samborska Małgorzata
Published: January 2016

Słowa, słowa... Czy je znasz? edited by Teresa Smółkowa (Kraków 2013), despite the fact that it has been recorded the male equivalents (eg. lack of forms jajcara, siecioholiczka, zasiłkowiczka, although there are jajcarz, siecioholik, zasiłkowicz). The authors proved the presence of such potential female names in the National Corpus of Polish and on the Internet using Google search. Of the 263 units unrecorded in the lexicon until 218 are present – with varying attendance – in the tested texts. This means that these female names are present in the social use. They do not limit themselves to the female equivalent of male names of professions. They also include semantic categories such as sports and hobbies, and names: representatives of certain attitudes and beliefs, women with specific characteristics of mental (including addicted women) and physical (including sick women), Internet users (including online offenders). These names are the result of suffixal derivation, mainly using the suffix -ka, eg. erasmuska < erasmus, netoholiczka < netoholik (but also such as: -ini/-yni, -ica/-yca, -anka and -ara), and the paradigmatic derivation, eg. dredziara < dredziarz, sprawna inaczej < sprawny inaczej. Functioning described in the article female names in the social circuit is proof that in the past ten years there has been a significant change in the Polish language in the pragmatic aspects of the nomination of women.
„Zgromadziła nas miłość”. Językowy obraz miłości w homiliach ślubnych
Authors: Rybka Małgorzata , Sławek Jolanta
Published: January 2016

The aim of this paper is to present the linguistic image of love derived from the wedding sermons published in the Internet. The idea of love is rarely defined in the analyzed texts and it is rarely presented in different aspects. Love is presented in the positive way by repeating the same, mostly conventionalized metaphors. What is more, the idea of love in the analyzed texts is stereotyped and schematic, because the authors of sermons refer to the common texts such as St. Paul Hymn to Love or different examples from everyday life. On the on hand, language of the sermons resembles the science and theological language that is not understandable for recipients, and on the other hand it is colloquial with the huge amount of expressive words.
Operowanie językiem w poszukiwaniu sensu oryginału
Authors: Tanuszewska Lidia
Published: January 2016

This article is about the translation as a process which changes the way of thinking in the other language, the one in which we translate. In order to make that text understandable for readers, the translator needs to make some changes in the original text, i.e. to manipulate with the language, so that the translation will transfer the same meaning and sense of the original one. Paraphrase is one of the strategies that is presented in this work.
Candida Royalle, 1950–2015
Authors: Penley Constance
Published: January 2016

Feminist scholar Constance Penley reflects on the contributions of the late Candida Royalle (1950-2015) on independent filmmaking, the adult film industry, sexual health education, the sex positive movement, and First Amendment activism.
Austen’s Literary Alembic
Authors: Tate Gregory
Published: January 2016

Gregory Tate, “Austen’s Literary Alembic: Sanditon, Medicine, and the Science of the Novel” (pp. 336–362)

This essay examines the representation of science in Jane Austen’s unfinished novel Sanditon. It argues that this text, written in the months before Austen’s death in 1817, points to a development in her understanding of the novel, one that associates the form with the emerging scientific disciplines of the early nineteenth century through its emphasis on empirical objectivity and professional expertise. These traits are exemplified in the medical profession, which is central to Sanditon’s plot. Austen’s text presents a range of different types of medical knowledge and practice, and it celebrates professional medical advice as a safe middle ground between the commercial exploitation of quackery and the uninformed subjectivism of hypochondria. Similar issues are at stake in the text’s considerations of the literary marketplace: while acknowledging some of the problems involved in the growing commodification of the novel, Sanditon also satirizes the undisciplined reading habits of careless readers, and it promotes a view of the novel as an objective and professional articulation of knowledge. Sanditon’s advocacy of professional objectivity is conveyed in its narrative stance as well as its plot: the text focuses not on the subjectivity of a single protagonist but on the objective observation and experimental comparison of the interactions between a number of characters and between those characters and their environment. The essay concludes that the methodologies of science, as they were practiced within the medical profession, played a significant part in Austen’s understanding of the profession of writing at the end of her career.
Penicillamine prevents ram sperm agglutination in media that support capacitation
Authors: Leahy T , Rickard J P , Aitken R J , de Graaf S P
Published: January 2016

Ram spermatozoa are difficult to capacitatein vitro. Here we describe a further complication, the unreported phenomenon of head-to-head agglutination of ram spermatozoa following dilution in the capacitation medium Tyrodes plus albumin, lactate and pyruvate (TALP). Sperm agglutination is immediate, specific and persistent and is not associated with a loss of motility. Agglutination impedesin vitrosperm handling and analysis. So the objectives of this study were to investigate the cause of sperm agglutination and potential agents which may reduce agglutination. The percentage of non-agglutinated, motile spermatozoa increased when bicarbonate was omitted from complete TALP suggesting that bicarbonate ions stimulate the agglutination process.d-penicillamine (PEN), a nucleophilic thiol, was highly effective at reducing agglutination. The inclusion of 250 μM PEN in TALP reduced the incidence of motile, agglutinated spermatozoa from 76.7±2.7% to 2.8±1.4%. It was then assessed if PEN (1 mM) could be included in existing ram sperm capacitation protocols (TALP +1 mM dibutyryl cAMP, caffeine and theophylline) to produce spermatozoa that were simultaneously capacitated and non-agglutinated. This protocol resulted in a sperm population which displayed high levels of tyrosine phosphorylated proteins and lipid disordered membranes (merocyanine-540) while remaining motile, viable, acrosome-intact and non-agglutinated. In summary, PEN (1 mM) can be included in ram sperm capacitation protocols to reduce sperm agglutination and allow for thein vitroassessment of ram sperm capacitation.