bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of institutional entrepreneurship in building adaptive capacity in community-based healthcare organisations: realist review protocol
Authors: Iyengar Sweatha , Katz Aaron , Durham Jo 
Published: March 2016

IntroductionOver the past 3 decades, there has been a substantial shift to the marketisation of government-funded health services. For organisations traditionally buffered from the competitive pressures of for-profit enterprises, such as community-based organisations, this means developing the capacity to adapt to competitive tendering processes, shifting client expectations, and increasing demands for greater accountability. Drawing on ideas of institutional entrepreneurship, we believe that attempts to build adaptive capacity require the transformation of existing institutional arrangements. Key in this may be identifying and fostering institutional entrepreneurs—actors who take the lead in being the impetus for, and giving direction to, structural change. This study focuses on the strategies used by institutional entrepreneurs to build adaptive capacity in the community-based healthcare sector.Methods and analysisThe research will use an adapted rapid realist review. The review will find underlying theories that explain the circumstances surrounding the implementation of capacity-building strategies that shape organisational response and generate outcomes by activating causal mechanisms. An early scoping of the literature, and consultations with key stakeholders, will be undertaken to identify an initial programme theory. We will search for relevant journal articles and grey literature. Data will be extracted based on contextual factors, mechanisms and outcomes, and their configurations. The analysis will seek patterns and regularities in these configurations and will focus on confirming, refuting or refining our programme theory.Ethics and disseminationThe study does not involve primary research and, therefore, does not require formal ethical approval. However, ethical standards of utility, usefulness, feasibility, propriety, accuracy and accountability will be followed. The results will be written up according to the Realist and Meta-Review Evidence Synthesis: Evolving Standards guidelines. Once completed, findings will be published in a peer-reviewed journal.Trial registration numberCRD42015026487.
Defining polypharmacy in the elderly: a systematic review protocol
Authors: Mortazavi Seyede Salehe , Shati Mohsen , Keshtkar Abasali , Malakouti Seyed Kazem , Bazargan Mohsen , Assari Shervin 
Published: March 2016

IntroductionAgeing—along with its associated physiological and pathological changes—places individuals at a higher risk of multimorbidity and treatment-related complications. Today, polypharmacy, a common and important problem related to drug use, occurs subsequent to this multimorbidity in the elderly in all populations. In recent decades, several scientific investigations have studied polypharmacy and its correlates, using different approaches and definitions, and their results have been inconclusive. Differences in definitions and approaches in these studies form a barrier against reaching a conclusion regarding the risk factors and consequences of polypharmacy. It is therefore imperative to establish an appropriate definition of polypharmacy.Methods and analysisA systematic review will be conducted using PubMed, Scopus, Web of Science, EMBASE, PsycINFO and AgeLine bibliographic databases, as well as the grey literature on polypharmacy in older adults to answer these two questions: What definitions in the literature are being used for polypharmacy in older people?, and Which definitions are more comprehensive and applicable? 2 independent reviewers will conduct the primary screening of the articles and data extraction, and eligible sources will be selected after discussing non-conformities. All extracted data from selected articles will be categorised based on the type of study participants, study design and setting, the methodological quality of primary studies and any other potential source of heterogeneity, and results will be summarised in a table, which will contain the levels of evidence and methodological quality of the included studies. The most comprehensive definition of polypharmacy will be selected from the final list of definitions through an international expert webinar.Ethics and DisseminationThis research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in a related peer-reviewed journal.
Effective strategies to motivate nursing home residents in oral healthcare and to prevent or reduce responsive behaviours to oral healthcare: a systematic review protocol
Authors: Hoben Matthias , Kent Angelle , Kobagi Nadia , Yoon Minn N 
Published: March 2016

IntroductionOral healthcare in nursing homes is less than optimal, with severe consequences for residents' health and quality of life. To provide the best possible oral healthcare to nursing home residents, care providers need strategies that have been proven to be effective. Strategies can either encourage and motivate residents to perform oral healthcare themselves or can prevent or overcome responsive behaviours from residents when care providers assist with oral healthcare. This systematic review aims to identify studies that evaluate the effectiveness of such strategies and to synthesise their evidence.Methods and analysisWe will conduct a comprehensive search in the databases MEDLINE, EMBASE, Evidence Based Reviews—Cochrane Central Register of Controlled Trials, CINAHL and Web of Science for quantitative intervention studies that assess the effectiveness of eligible strategies. 2 reviewers will independently screen titles, abstracts and retrieved full texts for eligibility. In addition, contents of key journals, publications of key authors and reference lists of all studies included will be searched by hand and screened by 2 reviewers. Discrepancies at any stage of the review process will be resolved by consensus. Data extraction will be performed by 1 research team member and checked by a second team member. 2 reviewers will independently assess methodological quality of studies included using 3 validated checklists appropriate for different research designs. We will present a narrative synthesis of study results.Ethics and disseminationWe did not seek ethics approval for this study, as we will not collect primary data and data from studies included cannot be linked to individuals or organisations. We will publish findings of this review in a peer-reviewed paper and present them at an international peer-reviewed conference.Trial registration numberCRD42015026439.
Factors associated with variation in hospital use at the end of life in England
Authors: Bardsley Martin , Georghiou Theo , Spence Ruth , Billings John 
Published: March 2016

ObjectiveTo identify the relative importance of factors influencing hospital use at the end of life.DesignRetrospective cohort study of person and health system effects on hospital use in the past 12 months modelling differences in admissions, bed days and whether a person died in hospital.SettingResidents in England for the period 2009/2010 to 2011/2012 using Hospital Episodes Statistics (HES) data from all acute care hospitals in England funded by the National Health Service (NHS).Participants1 223 859 people registered with a GP in England who died (decedents) in England (April 2009–March 2012) with a record of NHS hospital care.Main outcome measuresHospital admissions, and hospital bed days and place of death (in or out of hospital) in the past 12 months of life.ResultsThe mean number of admissions in the past 12 months of life averaged 2.28 occupying 30.05 bed days—excluding 9.8% of patients with no hospital history. A total of 50.8% of people died in hospital. Difference in hospital use was associated with a range of patient descriptors (age, gender and ethnicity). The variables with the greatest ‘explanatory power’ were those that described the diagnoses and causes of death. So, for example, 65% of the variability in the model of hospital admissions was explained by diagnoses. Only moderate levels of variation were explained by the hospital provider variables for admissions and deaths in hospital, though the impacts on total bed days was large.ConclusionsComparative analyses of hospital utilisation should standardise for a range of patient specific variables. Though the models indicated some degree of variability associated with individual providers, the scale of this was not great for admissions and death in hospital but the variability associated with length of stay differences suggests that attempts to optimise hospital use should look at differences in lengths of stay and bed use. This study adds important new information about variability in admissions by diagnostic group, and variability in bed days by diagnostic group and eventual cause of death.
Vascular invasion is an independent prognostic factor for distant recurrence-free survival in papillary thyroid carcinoma: a matched-case comparative study
Authors: Cao Jun , Hu Jin-Lin , Chen Can , Wang Qing-Liang , Fang Xian-Hua , Zhang Yan , Ge Ming-Hua 
Published: March 2016

ObjectiveIt is still unclear whether the clinicopathological and outcome characteristics of vascular invasion (VI) (+) papillary thyroid carcinoma (PTC) differ from VI (−) PTC. This study aims to establish distinguishing features of patients with VI (+) and VI (−) PTC and to investigate the biological and clinical aggressiveness of the disease in these patient groups.DesignA matched-case comparative study.Methods412 patients (VI (+) PTC study group n=103, and VI (−) PTC control group n=309). These two patient groups were matched 1:3 for variables of age, gender, histological variants, tumour/node/metastasis (TNM) staging and approximate duration of follow-up. Clinicopathological factors and prognosis were compared across the two patient groups.ResultsThe median age at the time of diagnosis was 42.0 years, and 68.9% were females. Across the patient groups, the incidence of tumour multifocality in patients with VI (+) PTC was slightly higher than in those with VI (−) PTC (p=0.049). In addition, when undergoing more aggressive therapy regimens patients with VI (+) PTC showed decreased distant recurrence-free survival (DRFS), but not regional recurrence-free survival (RRFS) and disease-specific survival (DSS) compared with patients who were VI (−). VI was found to be an independent predictor of DRFS, combined with tumour size >3 cm and total thyroidectomy.ConclusionsVI was an independent risk factor for DRFS, necessitating the need for appropriate postoperative treatment and careful follow-up.
Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics
Authors: Papagiannaki Chrysanthi , Clarençon Frédéric , Ponsonnard Sébastien , Couquet Claude , Maizeroi-Eugène Franck , Bresson Damien , Yardin Catherine , Mounayer Charbel 
Published: March 2016

BackgroundAngiogenesis has a key role in the formation and evolution of brain arteriovenous malformations (AVMs). Numerous models have been developed aiming to recreate configuration of brain AVMs.ObjectiveTo develop an animal model sharing the same pathological characteristics as human brain AVMs.Materials and methodsTen pigs were divided into two groups. Five animals underwent endovascular left common carotid artery (CCA) and external carotid artery (ECA) occlusion and five animals served as controls. DSA, associated with 3D-rotational angiography, was performed at day 0 and at 3 months in both groups. The volume of theretiawas calculated. Vascular endothelial growth factor (VEGF)-A serum levels were measured in both groups at the same time intervals. Finally, the animals were sacrificed at 3 months and theretiawere harvested for pathological and immunohistochemistry examinations.ResultsAt 3 months, a significantly higherretevolume was seen in group A than in group B (2.92±0.33 mL vs 1.87±0.69 mL, respectively; p=0.016). There was a trend for increased VEGF-A levels in group A at 3 months. In the occlusion group, histological findings showed significant reduction of media thickness and disrupted internal elastic lamina; immunohistochemistry findings showed strong reactivity for VEGF receptors and interleukin 6.ConclusionsUnilateral endovascular occlusion of the CCA–ECA results in angiogenesis triggering of therete mirabilewith both significant augmentation of theretevolume and histological evidence of pro-angiogenic stimulation.
HCl degassing from extremely acidic crater lakes: preliminary results from experimental determinations and implications for geochemical monitoring
Authors: Capaccioni B. , Rouwet D. , Tassi F. 
Published: March 2016

Abstract

Crater lakes are monitored to detect volcanic unrest starting from the assumption that they behave as condensers for magmatic gases. A further assumption is that acidic gases such as HCl are conservative once dissolved in water. This is not true for extremely acidic crater lakes, whose H
+
activity is high enough to induce Cl
−
hydrolysis and consequently HCl degassing. This study presents the results of experimental determinations at 40–45°C demonstrating that HCl degassing from acidic water depends on pH and Cl
−
concentration. HCl degassing starts at pH values
c.
0.05–0.1 with a rate of 5–10 mg min
−1
l
−1
, increasing up to
c.
70 mg min
−1
l
−1
at pH<−0.2. This implies that the rate of HCl removal from a crater lake with a volume of 10
4
–10
5
m
3
and a seawater-like Cl
−
concentration ranges from 5 to 50 t h
−1
. The estimated HCl/H
2
O ratio in the separated vapour phase (0.01–0.2) is coherent with HCl/H
2
O ratios of fumaroles. Our experiments imply that: (i) the presence of very acidic gas species in fumaroles can be associated with a liquid-dominated feeding system, and (ii) dissolved in extremely acidic crater lakes, Cl
−
behaves as a non-conservative component.
Evaluating a volcanic ash ground-loading hazard at Gunung Ciremai, West Java, Indonesia using PF3D
Authors: Bear-Crozier A. N. , Kartadinata N. , Heriwaseso A. , Nielsen O. 
Published: March 2016

Abstract
Volcanic ash represents a serious hazard to communities living in the vicinity of active volcanoes in developing countries such as Indonesia. Geoscience Australia (GA), the Australia–Indonesia Facility for Disaster Reduction (AIFDR) and Badan Geologi (Indonesia's Geological Agency) have adapted an existing open-source volcanic ash dispersion model for use in Indonesia. An application example is presented here for Gunung Ciremai in West Java, Indonesia. A stochastic set of eruption events was simulated using eruptive parameters within the acceptable range of possible future events for this volcano: granulometry and a meteorological dataset that represents the complete range of possible wind conditions expected during seasonal wind conditions for the region. Implications for nearby communities of dry v. rainy season conditions on volcanic ash hazard were investigated. Communities on the western side of Gunung Ciremai were highly susceptible to volcanic ash ground loading regardless of the season: communities on the eastern side, however, were more susceptible during the rainy season months. This is attributed to prevailing wind conditions during the rainy season that include a strong easterly component. Disaster risk reduction workers can use hazard maps like those produced here to inform decision-making, and to focus mitigation efforts on communities most at risk.
Editorial
Authors: Hart Emma 
Published: March 2016

This issue of SIGEVOLution is dedicated to the memory of John Holland, inventor of Genetic Algorithms, who sadly passed away on August 9th 2015. John's work will have touched all of us working in the field of Evolutionary Computing in some way big or small, from the PhD student just beginning to those who began work in the field at its inception. It was reading his book "Adaptation in Natural Artificial Systems" while I was an MSc student in 1994 that inspired me to go on to do first a Master's project and then a PhD in the area and I'm sure the same goes for so many other people reading this.
It is clearly impossible to do justice to such a figure in the few short pages of this newsletter. My grateful thanks go to Una-May O-Reilly who has been hugely helpful in suggesting names and collecting material for this issue. We have tried to pay tribute by gathering together contributions from many of those who worked directly with John during his long and rich career. In addition, we have interviews and contributions from several of his former graduate students, people who were inspired by his classes, and those that went on to work with him. The newsletter also highlights some of the tributes that were paid in various forms of the media, including a radio programme, a recent book published to celebrate his 85th birthday, and a look back to an interview with him published in the SIGEVO newsletter in 2008. Interviews and contributions are presented here in no particular order.
What ever you are currently working on in the broad, diverse and flourishing field of Evolutionary Computing today, it is doubtless underpinned by John's original ideas - I hope that you enjoy reading these insights into John the man and the scientist who paved the way for us!
Enfortumab Vedotin Antibody–Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models
Authors: Challita-Eid Pia M. , Satpayev Daulet , Yang Peng , An Zili , Morrison Karen , Shostak Yuriy , Raitano Arthur , Nadell Rossana , Liu Wendy , Lortie Dawn Ratay , Capo Linnette , Verlinsky Alla , Leavitt Monica , Malik Faisal , Aviña Hector , Guevara Claudia I. , Dinh Nick , Karki Sher , Anand Banmeet S. , Pereira Daniel S. , Joseph Ingrid B.J. , Doñate Fernando , Morrison Kendall , Stover David R. 
Published: March 2016

Abstract
The identification of optimal target antigens on tumor cells is central to the advancement of new antibody-based cancer therapies. We performed suppression subtractive hybridization and identified nectin-4 (PVRL4), a type I transmembrane protein and member of a family of related immunoglobulin-like adhesion molecules, as a potential target in epithelial cancers. We conducted immunohistochemical analysis of 2,394 patient specimens from bladder, breast, lung, pancreatic, ovarian, head/neck, and esophageal tumors and found that 69% of all specimens stained positive for nectin-4. Moderate to strong staining was especially observed in 60% of bladder and 53% of breast tumor specimens, whereas the expression of nectin-4 in normal tissue was more limited. We generated a novel antibody–drug conjugate (ADC) enfortumab vedotin comprising the human anti-nectin-4 antibody conjugated to the highly potent microtubule-disrupting agent MMAE. Hybridoma (AGS-22M6E) and CHO (ASG-22CE) versions of enfortumab vedotin (also known as ASG-22ME) ADC were able to bind to cell surface–expressed nectin-4 with high affinity and induced cell death in vitro in a dose-dependent manner. Treatment of mouse xenograft models of human breast, bladder, pancreatic, and lung cancers with enfortumab vedotin significantly inhibited the growth of all four tumor types and resulted in tumor regression of breast and bladder xenografts. Overall, these findings validate nectin-4 as an attractive therapeutic target in multiple solid tumors and support further clinical development, investigation, and application of nectin-4–targeting ADCs. Cancer Res; 76(10); 3003–13. ©2016 AACR.
miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells
Authors: Zhang Hong-Mei , Li Qing , Zhu Xiaojian , Liu Wei , Hu Hui , Liu Teng , Cheng Fanjun , You Yong , Zhong Zhaodong , Zou Ping , Li Qiubai , Chen Zhichao , Guo An-Yuan 
Published: March 2016

AbstractEvidence is accumulating that extracellular microvesicles (MV) facilitate progression and relapse in cancer. Using a model in which MVs derived from K562 chronic myelogenous leukemia (CML) cells transform normal hematopoietic transplants into leukemia-like cells, we defined the underlying mechanisms of this process through gene-expression studies and network analyses of transcription factors (TF) and miRNAs. We found that antitumor miRNAs were increased and several defense pathways were initiated during the early phases of oncogenic transformation. Later, oncomiRs and genes involved in cell cycle, DNA repair, and energy metabolism pathways were upregulated. Regulatory network analyses revealed that a number of TFs and miRNAs were responsible for the pathway dysregulation and the oncogenic transformation. In particular, we found that miR-146b-5p, which was highly expressed in MVs, coordinated the regulation of cancer-related genes to promote cell-transforming processes. Notably, treatment of recipient cells with MV derived from K562 cells expressing mimics of miR-146b-5p revealed that it accelerated the transformation process in large part by silencing the tumor-suppressor NUMB. High levels of miR-146b-5p also enhanced reactive oxygen species levels and genome instability of recipient cells. Taken together, our finding showed how upregulation of oncogenic miRNAs in MVs promote hematopoetic cells to a leukemic state, as well as a demonstration for TF and miRNA coregulatory analysis in exploring the dysregulation of cancers and discovering key factors. Cancer Res; 76(10); 2901–11. ©2016 AACR.
JPO2/CDCA7L and LEDGF/p75 Are Novel Mediators of PI3K/AKT Signaling and Aggressive Phenotypes in Medulloblastoma
Authors: Chan Tiffany Sin Yu , Hawkins Cynthia , Krieger Jonathan R. , McGlade C. Jane , Huang Annie 
Published: March 2016

Abstract
Substantial evidence links Myc–PI3K/AKT signaling to the most aggressive subtype of medulloblastoma and this axis in medulloblastoma therapy. In this study, we advance understanding of how Myc–PI3K/AKT signaling contributes to this malignancy, specifically, in identifying the Myc-interacting protein JPO2 and its partner binding protein LEDGF/p75 as critical modulators of PI3K/AKT signaling and metastasis in medulloblastoma. JPO2 overexpression induced metastatic medulloblastoma in vivo through two synergistic feed-forward regulatory circuits involving LEDGF/p75 and AKT that promote metastatic phenotypes in this setting. Overall, our findings highlight two novel prometastatic loci in medulloblastoma and point to the JPO2:LEDGF/p75 protein complex as a potentially new targetable component of PI3K/AKT signaling in medulloblastoma. Cancer Res; 76(9); 2802–12. ©2016 AACR.