bluuebunny/crossref_metadata_2025 huggingface dataset:
Robust BRCA1‐like classification of copy number profiles of samples repeated across different datasets and platforms
Authors: Schouten Philip C. , Grigoriadis Anita , Kuilman Thomas , Mirza Hasan , Watkins Johnathan A. , Cooke Saskia A. , van Dyk Ewald , Severson Tesa M. , Rueda Oscar M. , Hoogstraat Marlous , Verhagen Caroline V.M. , Natrajan Rachael , Chin Suet-Feung , Lips Esther H. , Kruizinga Janneke , Velds Arno , Nieuwland Marja , Kerkhoven Ron M. , Krijgsman Oscar , Vens Conchita , Peeper Daniel , Nederlof Petra M. , Caldas Carlos , Tutt Andrew N. , Wessels Lodewyk F. , Linn Sabine C.
Published: April 2015

Breast cancers with BRCA1 germline mutation have a characteristic DNA copy number (CN) pattern. We developed a test that assigns CN profiles to be ‘BRCA1‐like’ or ‘non‐BRCA1‐like’, which refers to resembling a BRCA1‐mutated tumor or resembling a tumor without a BRCA1 mutation, respectively. Approximately one third of the BRCA1‐like breast cancers have a BRCA1 mutation, one third has hypermethylation of the BRCA1 promoter and one third has an unknown reason for being BRCA1‐like. This classification is indicative of patients' response to high dose alkylating and platinum containing chemotherapy regimens, which targets the inability of BRCA1 deficient cells to repair DNA double strand breaks. We investigated whether this classification can be reliably obtained with next generation sequencing and copy number platforms other than the bacterial artificial chromosome (BAC) array Comparative Genomic Hybridization (aCGH) on which it was originally developed.

We investigated samples from 230 breast cancer patients for which a CN profile had been generated on two to five platforms, comprising low coverage CN sequencing, CN extraction from targeted sequencing panels (CopywriteR), Affymetrix SNP6.0, 135K/720K oligonucleotide aCGH, Affymetrix Oncoscan FFPE (MIP) technology, 3K BAC and 32K BAC aCGH. Pairwise comparison of genomic position‐mapped profiles from the original aCGH platform and other platforms revealed concordance. For most cases, biological differences between samples exceeded the differences between platforms within one sample. We observed the same classification across different platforms in over 80% of the patients and kappa values of at least 0.36. Differential classification could be attributed to CN profiles that were not strongly associated to one class. In conclusion, we have shown that the genomic regions that define our BRCA1‐like classifier are robustly measured by different CN profiling technologies, providing the possibility to retro‐ and prospectively investigate BRCA1‐like classification across a wide range of CN platforms.
Plasma membrane gp96 enhances invasion and metastatic potential of liver cancer via regulation of uPAR
Authors: Hou Junwei , Li Xin , Li Changfei , Sun Lu , Zhao Yulai , Zhao Jingmin , Meng Songdong
Published: April 2015

Targeted therapy is currently under intensive investigation due to the resistance of liver cancer to cytotoxic chemotherapies. Dissecting the molecular events that drive the progression of liver cancer and defining specific targets are urgently needed to develop efficient tailored therapies. Cell membrane gp96 (mgp96) has been implicated in tumor growth and malignancy. Here, we explored the functional and clinical relevance of mgp96 in liver cancer. We found that elevated mgp96 abundance was associated with tumor metastasis and recurrence in patients with primary liver tumors. Decreased KDELR1 levels in hepatoma cells contribute to cell membrane translocation of the normally ER‐resident gp96. Urokinase‐type plasminogen activator receptor (uPAR) was identified as a mgp96 client protein, and mgp96 stabilized uPAR protein. Our clinical results proved that elevated mgp96 abundance is positively correlated with uPAR expression levels in liver tumors. We further provided evidence that targeting mgp96 with siRNA or a specific mAb that blocked the mgp96‐uPAR interaction led to inhibited cell growth, survival, and invasion in vitro, as well as the suppression of liver tumor growth and metastasis in vivo. mgp96 promotes liver cancer progression through increasing the protein stability and signaling of uPAR, and may be a new promising target for suppressing uPAR‐mediated tumor growth and metastasis in liver cancer.
Firearms
Authors: Chase Kenneth
Published: April 2015

This book is a history of firearms across the world from the 1100s up to the 1700s, from their invention in China to the time when European firearms had become clearly superior. It asks why it was the Europeans who perfected firearms when it was the Chinese who had invented them, and answers this question by looking at how firearms were used throughout the world. Early firearms were restricted to infantry and siege warfare, limiting their use outside of Europe and Japan. Steppe and desert nomads imposed a different style of warfare on the Middle East, India, and China – a style with which firearms were incompatible. By the time that better firearms allowed these regions to turn the tables on the nomads, Japan's self-imposed isolation left Europe with no rival in firearms design, production, or use, with consequences that are still with us today.
The History and Design of the Foundling Hospital
Authors: Brownlow John
Published: April 2015

Captain Coram's Foundling Hospital was opened in London in 1741 for 'the maintenance and education of exposed and deserted young children'. Hogarth was a governor of the hospital - he donated several pictures, including his portrait of Coram - as was Handel, whose famous performances of his oratorio Messiah were given there from 1750 to raise funds. John Brownlow (1800–73), himself a foundling, became secretary of the hospital from 1849 until his retirement. He introduced improvements to the children's education and was a staunch defender of the hospital, refuting criticisms often levelled in the nineteenth century that taking in illegitimate children simply encouraged neglect. This brief account, building on his 1847 Memoranda, or, Chronicles of the Foundling Hospital (also reissued in this series), covers Coram, early supporters, the institution's paintings - which formed the first public art gallery in London - and the care of the foundlings.
Forests in Revolutionary France
Authors: Matteson Kieko
Published: April 2015

This book investigates the economic, strategic, and political importance of forests in early modern and modern Europe and shows how struggles over this vital natural resource both shaped and reflected the ideologies and outcomes of France's long revolutionary period. Until the mid-nineteenth century, wood was the principal fuel for cooking and heating and the primary material for manufacturing worldwide and comprised every imaginable element of industrial, domestic, military, and maritime activity. Forests also provided essential pasturage. These multifaceted values made forests the subject of ongoing battles for control between the crown, landowning elites, and peasantry, for whom liberty meant preserving their rights to woodland commons. Focusing on Franche-Comté, France's easternmost province, the book explores the fiercely contested development of state-centered conservation and management from 1669 to 1848. In emphasizing the environmental underpinnings of France's seismic sociopolitical upheavals, it appeals to readers interested in revolution, rural life, and common-pool-resource governance.
Papacy, Monarchy and Marriage 860–1600
Authors: d'Avray David
Published: April 2015

This analysis of royal marriage cases across seven centuries explains how and how far popes controlled royal entry into and exits from their marriages. In the period between c.860 and 1600, the personal lives of kings became the business of the papacy. d'Avray explores the rationale for papal involvement in royal marriages and uses them to analyse the structure of church-state relations. The marital problems of the Carolingian Lothar II, of English kings - John, Henry III, and Henry VIII - and other monarchs, especially Spanish and French, up to Henri IV of France and La Reine Margot, have their place in this exploration of how canon law came to constrain pragmatic political manoeuvring within a system increasingly rationalised from the mid-thirteenth century on. Using documents presented in the author's Dissolving Royal Marriages, the argument brings out hidden connections between legal formality, annulments, and dispensations, at the highest social level.
Core Statistics
Authors: Wood Simon
Published: April 2015

Based on a starter course for beginning graduate students, Core Statistics provides concise coverage of the fundamentals of inference for parametric statistical models, including both theory and practical numerical computation. The book considers both frequentist maximum likelihood and Bayesian stochastic simulation while focusing on general methods applicable to a wide range of models and emphasizing the common questions addressed by the two approaches. This compact package serves as a lively introduction to the theory and tools that a beginning graduate student needs in order to make the transition to serious statistical analysis: inference; modeling; computation, including some numerics; and the R language. Aimed also at any quantitative scientist who uses statistical methods, this book will deepen readers' understanding of why and when methods work and explain how to develop suitable methods for non-standard situations, such as in ecology, big data and genomics.
Bioarchaeology
Authors: Larsen Clark Spencer
Published: April 2015

Now including numerous full colour figures, this updated and revised edition of Larsen's classic text provides a comprehensive overview of the fundamentals of bioarchaeology. Reflecting the enormous advances made in the field over the past twenty years, the author examines how this discipline has matured and evolved in fundamental ways. Jargon free and richly illustrated, the text is accompanied by copious case studies and references to underscore the central role that human remains play in the interpretation of life events and conditions of past and modern cultures. From the origins and spread of infectious disease to the consequences of decisions made by humans with regard to the kinds of foods produced, and their nutritional, health and behavioral outcomes. With local, regional, and global perspectives, this up-to-date text provides a solid foundation for all those working in the field.
The Politics of Market Discipline in Latin America
Authors: Campello Daniela
Published: April 2015

The Politics of Market Discipline in Latin America uses a multi-method approach to challenge the conventional wisdom that financial markets impose broad and severe constraints over leftist economic policies in emerging market countries. It shows, rather, that in Latin America, this influence varies markedly among countries and over time, depending on cycles of currency booms and crises exogenous to policy making. Market discipline is strongest during periods of dollar scarcity, which, in low-savings commodity-exporting countries, occurs when commodity prices are high and international interest rates low. In periods of dollar abundance, when the opposite happens, the market's capacity to constrain leftist governments is very limited. Ultimately, Daniela Campello argues that financial integration should force the Left toward the center in economies less subject to these cycles, but not in those most vulnerable to them.
Essays on Religion and Human Rights
Authors: Little David
Published: April 2015

This collection of essays by David Little addresses human rights in relation to the historical settings in which its language was drafted and adopted. Featuring five original essays, Little articulates his view that fascist practices before and during World War II vivified the wrongfulness of deliberately inflicting severe pain, injury, and destruction for self-serving purposes and that the human rights corpus, developed in response, was designed to outlaw all practices of arbitrary force. He contends that while there must be an accountable human rights standard, it should guarantee latitude for the expression and practice of beliefs, consistent with outlawing arbitrary force. Little details the theoretical grounds of the relationship between religion and human rights, and concludes with essays on US policy and the restraint of force in regard to terrorism. With a foreword by John Kelsey, this book is a capstone of the work of this influential writer on religion, philosophy, and law.
The Phonology of Consonants
Authors: Bennett Wm G.
Published: April 2015

The most comprehensive work on dissimilation (the avoidance or repair of combinations of similar sounds) to date, this book proposes a novel analysis that handles dissimilation as the avoidance of surface correspondence relationships. It draws on recent work in Agreement By Correspondence to show that dissimilation is a natural outcome predicted by the same theory of Surface Correspondence. The theory is developed in more detail than ever before, and its predictions are tested and evaluated through ten in-depth analyses of diverse languages from Quechua to Kinyarwanda, together with a typological survey of over 150 dissimilation patterns drawn from over 130 languages, from Acehnese to Zulu. The book redefines the core of Surface Correspondence theory to a level of formal specificity and theoretical precision surpassing previous work. The book's findings are made more accessible by numerous examples featuring data from 47 languages from around the world.
Silicon Photonics Design
Authors: Chrostowski Lukas , Hochberg Michael
Published: April 2015

From design and simulation through to testing and fabrication, this hands-on introduction to silicon photonics engineering equips students with everything they need to begin creating foundry-ready designs. In-depth discussion of real-world issues and fabrication challenges ensures that students are fully equipped for careers in industry. Step-by-step tutorials, straightforward examples, and illustrative source code fragments guide students through every aspect of the design process, providing a practical framework for developing and refining key skills. Offering industry-ready expertise, the text supports existing PDKs for CMOS UV-lithography foundry services (OpSIS, ePIXfab, imec, LETI, IME and CMC) and the development of new kits for proprietary processes and clean-room based research. Accompanied by additional online resources to support students, this is the perfect learning package for senior undergraduate and graduate students studying silicon photonics design, and academic and industrial researchers involved in the development and manufacture of new silicon photonics systems.
Active Radar Cross Section Reduction
Authors: Singh Hema , Jha Rakesh Mohan
Published: April 2015

This book discusses the active and passive radar cross section (RCS) estimation and techniques to examine the low observable aerospace platforms. It begins with the fundamentals of RCS, followed by the dielectric, magnetic and metamaterials parameters of the constituent materials and then explains various methods and the emerging trends followed in this area of study. The RCS estimation of phased array including the mutual coupling effect is also presented in detail in the book. The active RCS reduction is carefully touched upon through the performance of phased arrays, sidelobe cancellers and mitigation of multipath effect. Providing information on various adaptive algorithms like least mean square (LMS), recursive least square (RLS) and weighted least square algorithms, the authors also mention the recent developments in the area of embedded antennas, conformal load bearing antenna, metamaterials and frequency selective surface (FSS) based RCS reduction.
A Printed Icon in Early Modern Italy
Authors: Pon Lisa
Published: April 2015

In 1428, a devastating fire destroyed a schoolhouse in the northern Italian city of Forlì, leaving only a woodcut of the Madonna and Child that had been tacked to the classroom wall. The people of Forlì carried that print - now known as the Madonna of the Fire - into their cathedral, where two centuries later a new chapel was built to enshrine it. In this book, Lisa Pon considers a cascade of moments in the Madonna of the Fire's cultural biography: when ink was impressed onto paper at a now-unknown date; when that sheet was recognized by Forlì's people as miraculous; when it was enshrined in various tabernacles and chapels in the cathedral; when it or one of its copies was - and still is - carried in procession. In doing so, Pon offers an experiment in art historical inquiry that spans more than three centuries of making, remaking, and renewal.
From Treaty-Making to Treaty-Breaking
Authors: Kuijper Pieter Jan , Mathis James H. , Morris-Sharma Natalie Y.
Published: April 2015

From Treaty-Making to Treaty-Breaking is the first high-level analysis of ASEAN's external trade agreements with non-ASEAN states. It clearly sets out the intended, and unintended, consequences of ASEAN's prevailing method of treaty making, with suggested guidelines for the future. The book begins by asking whether ASEAN trade agreements follow worldwide trends in the substantive content of such agreements. It raises questions such as: to what extent is it possible to continue concluding trade agreements through individual member states?; what are the legal consequences - from negotiation and conclusion (treaty-making) through to possible breach of the agreements (treaty-breaking)?; should ASEAN resort to mixed treaty-making? This study does not seek to give a definitive answer to these questions, rather it opens up the topic to readers by suggesting different possible models for ASEAN trade agreements. This thought-provoking book will appeal to anyone interested in trade negotiations and trade agreements, particularly in Asia.
High-frequency forcing of a turbulent axisymmetric wake
Authors: Oxlade Anthony R. , Morrison Jonathan F. , Qubain Ala , Rigas Georgios
Published: April 2015

A high-frequency periodic jet, issuing immediately below the point of separation, is used to force the turbulent wake of a bluff axisymmetric body, its axis aligned with the free stream. It is shown that the base pressure may be varied more or less at will: at forcing frequencies several times that of the shear layer frequency, the time-averaged area-weighted base pressure increases by as much as 35 %. An investigation of the effects of forcing is made using random and phase-locked two-component particle image velocimetry (PIV), and modal decomposition of pressure fluctuations on the base of the model. The forcing does not target specific local or global wake instabilities: rather, the high-frequency jet creates a row of closely spaced vortex rings, immediately adjacent to which are regions of large shear on each side. These shear layers are associated with large dissipation and inhibit the entrainment of fluid. The resulting pressure recovery is proportional to the strength of the vortices and is accompanied by a broadband suppression of base pressure fluctuations associated with all modes. The optimum forcing frequency, at which amplification of the shear layer mode approaches unity gain, is roughly five times the shear layer frequency.
Forsaking their ‘own flesh and blood’? Ulster unionism, Scotland and home rule, 1886–1914
Authors: Dunn Peter
Published: April 2015

Writing to a ‘Friend in Scotland’, in 1888, the Rev. Hugh Hanna declared: ‘it is the duty of Christian people in these lands to do the best they can for all parts of the United Kingdom’. Having explained why Irish Protestants were opposed to home rule, he then asked how any

section of Scotch Presbyterians should support that policy, and array itself in antagoism to their kinsmen in Ireland? Is it possible that political partisanship can dominate all the considerations of a common lineage and a common faith, and that any part of Scotland would forsake its own flesh and blood to promote the policy and restore the power of a fallen leader ...?
‘War is a Scourge’: The First Year of the Great War 1914–1915: Catholics and Pastoral Guidance
Authors: Davies John
Published: April 2015

When Britain declared war on Germany in August 1914 few could have foreseen that it would last four years or predicted the slaughter it would bring. The parishioners of the Catholic parish of St. Peter Seel St., in the docklands of south Liverpool, along with Catholics throughout the country, on the first Sunday of the war were exhorted to pray for peace. The assumption seemed to be that the war would be a short one. The lessons of Britain's last major conflict, the South African Wars at the turn of the nineteenth-century, seemed not to have impinged on popular imagination. it would, however, be only a relatively short space of time before the news of local young men ‘killed in action’ began to appear in the notice books of St. Peter's and other Catholic parishes, bringing a growing realisation that this war was ‘different’. Perhaps it would not end quickly and certainly as the horror of events in Belgium and France began to appear in the press, national, local and ‘confessional’, the conviction grew that indeed this was no ‘ordinary’ war. How did the leaders of the Catholic community respond? What guidance and comfort were offered to the community, which was largely working class, whose sons found themselves in the front line?
Comparative analyses of speech and language converge on birds
Authors: Beckers Gabriël J. L. , Berwick Robert C. , Bolhuis Johan J.
Published: April 2015

Unlike nonhuman primates, thousands of bird species have articulatory capabilities that equal or surpass those of humans, and they develop their vocalizations through vocal imitation in a way that is very similar to how human infants learn to speak. An understanding of how speech mechanisms have evolved is therefore unlikely to yield key insights into how the human brain is special.
Authors and Rappers: Italian Hip Hop and the Shifting Boundaries of Canzone d’Autore
Authors: SANTORO MARCO , SOLAROLI MARCO
Published: April 2015

By offering a historical reconstruction of the process of contextualisation of hip hop culture in Italy over the last fifteen years, the article assesses the current status of canzone d’autore and its changing configuration under the impact of rap music. From a theoretical point of view, the conceptual framework combines the sociological definition of ‘field of cultural production’ elaborated by Pierre Bourdieu with the related literature on social and symbolic boundaries. From a methodological point of view, the analysis is based on the data collected by Club Tenco (a cultural organisation which plays an institutional role within the field of canzone d’autore) as well as on a series of qualitative interviews carried out with a number of Italian rappers and cantautori. Special attention is paid to a very few crucial figures that can be considered paradigmatic examples in the dynamic process of boundary-making of the two cultural (sub-)fields of Italian rap and canzone d’autore.
Producing beef for an identified market
Authors: Jobst D. , Williams R. G.
Published: April 2015

The beef programme set up by Dalgety Meat Ltd is a positive link between producer and consumer. It started 10 years ago when it became clear that it was necessary for Dalgety to establish a link with beef breeding and production if the company was to provide its retail clients with regular supplies of quality meat. To achieve this link, Dalgety Meat Ltd developed beef producer groups.

Calves destined for beef originate either from dairy or beef herds and there are many different routes through life, making it very difficult to maintain contact with the product from conception to consumer. Also, an individual producer fattening, say, 50 to 100 head, supplying a wholesaler requiring 50,100 or 200 thousand cattle per year can not, individually, make any impact in terms of producing beef for an identified market. However, a group of producers with an output of several thousand fat cattle opens up a different possibility.
Efficacy of a cognitive stimulation therapy programme for people with dementia
Authors: Coen Robert F , Flynn Bronagh , Rigney Edel , O'Connor Elaine , Fitzgerald Liza , Murray Ciaran , Dunleavy Catherine , McDonald Mindy , Delaney Deirdre , Merriman Niamh , Edgeworth Jennifer
Published: April 2015

Objectives: Cognitive stimulation therapy (CST) has been shown to produce improvements in cognition and quality of life which compare favourably with trials of cholinesterase inhibitors. The aim of the present study was to evaluate the efficacy of CST, replicating the methods of Spector et al in the British Journal of Psychiatry in 2003 in a smaller sample using a control group engaged in routine activities.

Methods: Eligible participants (mild to moderate dementia; MMSE range 10-23) were randomised to CST group or control conditions. Pre- and post-intervention testing was undertaken by assessors who were blind to condition. Measures included MMSE, CDR (sum of boxes), ADAS-cog, RAID (anxiety), abbreviated GDS (depression), QoL-AD, and the CAPE Behaviour Rating Scale (BRS). Analysis was by non-parametric statistics. Occupational therapists facilitated two sessions per week for seven weeks in two long-term care facilities and the same programme was run by the activity co-ordinator in a nursing home unit.

Results: Fourteen CST and 13 control participants completed the study. Between group difference scores analysis showed that the CST group improved compared to controls on MMSE (Mann-Whitney U = 32, p = 0.013) and on the QoL-AD which just fell short of significant (U=51.5, p = 0.055). Qualitatively, therapists noted that CST participants demonstrated good interaction and enthusiasm in the group environment, with continuity and carryover between sessions.

Conclusions: Even though the sample sizes are small the current study is consistent with the Spector et al's findings in 2003 of beneficial effects in people with dementia following CST. The programme is recommended as an intervention for people with mild to moderate dementia.
Understanding the Health of Refugee Women in Host Countries: Lessons from the Kosovar Re-Settlement in Canada
Authors: Redwood-Campbell Lynda , Thind Harpreet , Howard Michelle , Koteles Jennifer , Fowler Nancy , Kaczorowski Janusz
Published: April 2015

Introduction:

Refugees from Kosovo arrived in several Canadian cities after humanitarian evacuations in 1999. Approximately 500 arrived in Hamilton, Canada. Volunteer sponsors from community organizations assisted the families with settlement, which included providing them access to healthcare services.

Hypothesis/Problem: It was anticipated that women, in particular, would have unmet health needs relating to trauma and a lack of healthcare access after experiencing forced migration.

Methods:

This study describes the results of a self-administered survey regarding women's health issues and experiences with health services after the arrival of refugees. It also describes the sponsor group's experience related to women's health care. The survey was administered to a random sample of 85 women refugees, and focus groups with 14 sponsors.Women self-completed questionnaires about their health, which included the Harvard Trauma Questionnaire for post-traumatic stress disorder (PTSD) and use of preventive health services. Sponsor groups participated in a focus group discussing healthcare needs and experiences of their assigned refugee families. Themes pertaining to women's issues were identified from the focus groups.

Results:

Preventive screening rates were low, only 1/19 (5.3%) women ≥50- years-old had ever received a mammogram; 34.1% (28/82) had ever received a Pap test); and PTSD was prevalent (25.9%, 22/85). Sponsor groups identified challenges relating to prenatal care needs, finding family physicians, language barriers to health care services, cultural influences of women's healthcare decision-making, mental health concerns, and difficulties accessing dental care, eye care, and prescriptions.

Conclusions:

Many women refugees from Kosovo had unmet health needs. Culturally appropriate population level screening campaigns and integration of language and interpretation services into the healthcare sector on a permanent basis are important policy actions to be adequately prepared for newcomers and women in displaced situations. These needs should be anticipated during the evacuation period by host countries to aid in planning the provision of health resources more efficiently for refugees and displaced people going to host countries.
Factors Associated with Workplace Violence in Paramedics
Authors: Koritsas Stella , Boyle Malcolm , Coles Jan
Published: April 2015

Introduction:

The majority of research that has explored workplace violence has focused on establishing the prevalence of violence in different settings. In general, there is a paucity of research that explores factors that may predict or increase the risk of experiencing violence in the workplace.

Objective:

The aim of this research was to determine predictors of violence for paramedics.

Methods:

A questionnaire was developed that focused on paramedics' experi-ences with six forms of violence: verbal abuse, property damage/theft, intimi-dation, physical abuse, sexual harassment, and sexual assault.The questionnaire was distributed randomly to paramedics throughout rural Victoria and metropolitan South Australia, and completed and returned anonymously.

Results:

Predictors emerged for verbal abuse, intimidation, sexual harassment, and sexual abuse. Specifically, gender was the only predictor of intimidation, sexual harassment, and sexual assault. Paramedic qualifications, how they responded to a call-out, and hours per week in direct patient contact emerged as a predictor of verbal abuse.

Conclusions:

Certain factors predict or predispose paramedics to workplace violence. The need for workplace violence education and training is impera-tive for the prevention of violence, as well as for its management.
Training Healthcare Personnel for Mass-Casualty Incidents in a Virtual Emergency Department: VED II
Authors: Heinrichs Wm. LeRoy , Youngblood Patricia , Harter Phillip , Kusumoto Laura , Dev Parvati
Published: April 2015

Introduction:

Training emergency personnel on the clinical management of a mass-casualty incident (MCI) with prior chemical, biological, radioactive, nuclear, or explosives (CBRNE)-exposed patients is a component of hospital preparedness procedures.

Objective:

The objective of this research was to determine whether a Virtual Emergency Department (VED), designed after the Stanford University Medical Center's Emergency Department (ED) and populated with 10 virtual patient victims who suffered from a dirty bomb blast (radiological) and 10 who suffered from exposure to a nerve toxin (chemical), is an effective clinical environment for training ED physicians and nurses for such MCIs.

Methods:

Ten physicians with an average of four years of post-training experience, and 12 nurses with an average of 9.5 years of post-graduate experience at Stanford University Medical Center and San Mateo County Medical Center participated in this IRB-approved study. All individuals were provided electronic information about the clinical features of patients exposed to a nerve toxin or radioactive blast before the study date and an orientation to the “game” interface, including an opportunity to practice using it immediately prior to the study. An exit questionnaire was conducted using a Likert Scale test instrument.

Results:

Among these 22 trainees, two-thirds of whom had prior Code Triage (multiple casualty incident) training, and one-half had prior CBRNE training, about two-thirds felt immersed in the virtual world much or all of the time. Prior to the training, only four trainees (18%) were confident about managing CBRNE MCIs. After the training, 19 (86%) felt either “confident” or “very confident”, with 13 (59%) attributing this change to practicing in the virtual ED. Twenty-one (95%) of the trainees reported that the scenarios were useful for improving healthcare team skills training, the primary objective for creating them. Eighteen trainees (82%) believed that the cases also were instructive in learning about clinical skills management of such incidents. Conclusions: These data suggest that training healthcare teams in online, virtual environments with dynamic virtual patients is an effective method of training for management of MCIs, particularly for uncommonly occurring incidents.

Conclusions:

These data suggest that training healthcare teams in online, virtual environments with dynamic virtual patients is an effective method of training for management of MCIs, particularly for uncommonly occurring incidents.
Towards continuing education and professional development: drivers for change in therapy radiography
Authors: Spalding M.
Published: April 2015

In recent years therapy radiographers, as one of the Allied Health Professions, have been subject to many initiatives, recommendations and professional and technical developments which have driven or encouraged them to increase their uptake of post-registration continuing education and professional development activities. These initiatives and drivers for change are diverse both in their source and in their degrees of influence and range from government legislation at a national level down to local initiatives. This paper identifies the main drivers affecting therapy radiographers with regard to these issues, evaluates their impact on the profession and discusses some of the barriers and limitations to the uptake of educational and CPD activities.
Using an OCD formulation in the treatment of anorexia nervosa: a useful way to understand the illness?
Authors: Jenkins Paul E.
Published: April 2015

Anorexia nervosa (AN) and obsessive compulsive disorder (OCD) have been shown to have a number of commonalities, such as genetics, neurobiology, and symptoms. Approaches to treatment of AN have recently been described that take such findings into account, extending interventions recommended for obsessive compulsive and anxiety disorders to AN. The current paper aims to outline a formulation model of AN in adults, derived from the literature on OCD, and introduce this topic as a fruitful area to build on existing treatment techniques, and to prompt further discussion of such techniques. A formulation model is described, followed by a discussion of how this might be applied to AN, using examples from clinical practice. Potential benefits and difficulties are discussed. A formulation model is suggested that can easily be adapted to AN, complementing existing models in eating disorders.
Greenhouse Gas Taxes on Meat Products: A Legal Perspective
Authors: Bähr Cordelia Christiane
Published: April 2015

Meat production and the transport sector contribute almost equally to global warming. However, unlike the transport sector, in terms of climate change policies meat production is relatively unregulated. Many scientists have called for a meat tax as a means of reducing consumption but governments and politicians have not responded. Has the law been an obstacle to the acceptance of a meat tax? To address that question, this article analyzes three examples of European Union (EU) taxes that could be imposed on the consumption of domestic and imported meat, and examines them in relation to the international climate change regime, human rights law, and the legal regimes of the World Trade Organization and the EU. It shows that, if carefully designed, an EU meat tax is consistent with these bodies of law. To address adequately the industrial sectors that give rise to global warming, governments will need to overcome the taboo relating to the concept of a meat tax.
Size-fraction partitioning of community gene transcription and nitrogen metabolism in a marine oxygen minimum zone
Authors: Ganesh Sangita , Bristow Laura A , Larsen Morten , Sarode Neha , Thamdrup Bo , Stewart Frank J
Published: April 2015

The genetic composition of marine microbial communities varies at the microscale between particle-associated (PA; >1.6 μm) and free-living (FL; 0.2–1.6 μm) niches. It remains unclear, however, how metabolic activities differ between PA and FL fractions. We combined rate measurements with metatranscriptomics to quantify PA and FL microbial activity in the oxygen minimum zone (OMZ) of the Eastern Tropical North Pacific, focusing on dissimilatory processes of the nitrogen (N) cycle. Bacterial gene counts were 8- to 15-fold higher in the FL compared with the PA fraction. However, rates of all measured N cycle processes, excluding ammonia oxidation, declined significantly following particle (>1.6 μm) removal. Without particles, rates of nitrate reduction to nitrite (1.5–9.4nmNd−1) fell to zero and N2 production by denitrification (0.5–1.7nmNd−1) and anammox (0.3–1.9nmNd−1) declined by 53–85%. The proportional representation of major microbial taxa and N cycle gene transcripts in metatranscriptomes followed fraction-specific trends. Transcripts encoding nitrate reductase were uniform among PA and FL fractions, whereas anammox-associated transcripts were proportionately enriched up to 15-fold in the FL fraction. In contrast, transcripts encoding enzymes for N2O and N2 production by denitrification were enriched up to 28-fold in PA samples. These patterns suggest that the majority of N cycle activity, excluding N2O and N2 production by denitrification, is confined to a FL majority that is critically dependent on access to particles, likely as a source of organic carbon and inorganic N. Variable particle distributions may drive heterogeneity in N cycle activity and gene expression in OMZs.
The solar magnetic activity band interaction and instabilities that shape quasi-periodic variability
Authors: McIntosh Scott W. , Leamon Robert J. , Krista Larisza D. , Title Alan M. , Hudson Hugh S. , Riley Pete , Harder Jerald W. , Kopp Greg , Snow Martin , Woods Thomas N. , Kasper Justin C. , Stevens Michael L. , Ulrich Roger K.
Published: April 2015

Solar magnetism displays a host of variational timescales of which the enigmatic 11-year sunspot cycle is most prominent. Recent work has demonstrated that the sunspot cycle can be explained in terms of the intra- and extra-hemispheric interaction between the overlapping activity bands of the 22-year magnetic polarity cycle. Those activity bands appear to be driven by the rotation of the Sun’s deep interior. Here we deduce that activity band interaction can qualitatively explain the ‘Gnevyshev Gap’—a well-established feature of flare and sunspot occurrence. Strong quasi-annual variability in the number of flares, coronal mass ejections, the radiative and particulate environment of the heliosphere is also observed. We infer that this secondary variability is driven by surges of magnetism from the activity bands. Understanding the formation, interaction and instability of these activity bands will considerably improve forecast capability in space weather and solar activity over a range of timescales.
Quantitative analysis of the TNF-α-induced phosphoproteome reveals AEG-1/MTDH/LYRIC as an IKKβ substrate
Authors: Krishnan Ramesh K. , Nolte Hendrik , Sun Tianliang , Kaur Harmandeep , Sreenivasan Krishnamoorthy , Looso Mario , Offermanns Stefan , Krüger Marcus , Swiercz Jakub M.
Published: April 2015

The inhibitor of the nuclear factor-κB (IκB) kinase (IKK) complex is a key regulator of the canonical NF-κB signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-κB activation; however, there is increasing evidence for NF-κB pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-α-IKKβ-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which ∼1% are regulated up on TNF-α stimulation. We identify various potential novel IKKβ substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKKβ on serine 298. We provide evidence that IKKβ-mediated AEG-1 phosphorylation is essential for IκBα degradation as well as NF-κB-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo.
IL-6-mediated environmental conditioning of defective Th1 differentiation dampens antitumour immune responses in old age
Authors: Tsukamoto Hirotake , Senju Satoru , Matsumura Keiko , Swain Susan L. , Nishimura Yasuharu
Published: April 2015

Decline in immune function and inflammation concomitantly develop with ageing. Here we focus on the impact of this inflammatory environment on T cells, and demonstrate that in contrast to successful tumour elimination in young mice, replenishment of tumour-specific CD4+ T cells fails to induce tumour regression in aged hosts. The impaired antitumour effect of CD4+ T cells with their defective Th1 differentiation in an aged environment is restored by interleukin (IL)-6 blockade or IL-6 deficiency. IL-6 blockade also restores the impaired ability of CD4+ T cells to promote CD8+ T-cell-dependent tumour elimination in aged mice, which requires IFN-γ. Furthermore, IL-6-stimulated production of IL-4/IL-21 through c-Maf induction is responsible for impaired Th1 differentiation. IL-6 also contributes to IL-10 production from CD4+ T cells in aged mice, causing attenuated responses of CD8+ T cells. These findings suggest that IL-6 serves as an extrinsic factor counteracting CD4+ T-cell-mediated immunity against tumour in old age.
Reduced Tyk2 gene expression in β-cells due to natural mutation determines susceptibility to virus-induced diabetes
Authors: Izumi Kenichi , Mine Keiichiro , Inoue Yoshitaka , Teshima Miho , Ogawa Shuichiro , Kai Yuji , Kurafuji Toshinobu , Hirakawa Kanako , Miyakawa Daiki , Ikeda Haruka , Inada Akari , Hara Manami , Yamada Hisakata , Akashi Koichi , Niho Yoshiyuki , Ina Keisuke , Kobayashi Takashi , Yoshikai Yasunobu , Anzai Keizo , Yamashita Teruo , Minagawa Hiroko , Fujimoto Shuji , Kurisaki Hironori , Shimoda Kazuya , Katsuta Hitoshi , Nagafuchi Seiho
Published: April 2015

Accumulating evidence suggests that viruses play an important role in the development of diabetes. Although the diabetogenic encephalomyocarditis strain D virus induces diabetes in restricted lines of inbred mice, the susceptibility genes to virus-induced diabetes have not been identified. We report here that novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the virus-resistant C57BL/6 background are highly sensitive to virus-induced diabetes. Tyk2 gene expression is strongly reduced in Tyk2-mutant mice, associated with low Tyk2 promoter activity, and leads to decreased expression of interferon-inducible genes, resulting in significantly compromised antiviral response. Tyk2-mutant pancreatic β-cells are unresponsive even to high dose of Type I interferon. Reversal of virus-induced diabetes could be achieved by β-cell-specific Tyk2 gene expression. Thus, reduced Tyk2 gene expression in pancreatic β-cells due to natural mutation is responsible for susceptibility to virus-induced diabetes.
Systematic functional profiling of transcription factor networks in Cryptococcus neoformans
Authors: Jung Kwang-Woo , Yang Dong-Hoon , Maeng Shinae , Lee Kyung-Tae , So Yee-Seul , Hong Joohyeon , Choi Jaeyoung , Byun Hyo-Jeong , Kim Hyelim , Bang Soohyun , Song Min-Hee , Lee Jang-Won , Kim Min Su , Kim Seo-Young , Ji Je-Hyun , Park Goun , Kwon Hyojeong , Cha Suyeon , Meyers Gena Lee , Wang Li Li , Jang Jooyoung , Janbon Guilhem , Adedoyin Gloria , Kim Taeyup , Averette Anna K. , Heitman Joseph , Cheong Eunji , Lee Yong-Hwan , Lee Yin-Won , Bahn Yong-Sun
Published: April 2015

Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). Here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative TF genes previously predicted using the DNA-binding domain TF database, and examine their in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and ∼85% of them (132/155) are functionally characterized for the first time in this study. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and human fungal pathogens.
Network Modularity is essential for evolution of cooperation under uncertainty
Authors: Gianetto David A. , Heydari Babak
Published: April 2015

Cooperative behavior, which pervades nature, can be significantly enhanced when agents interact in a structured rather than random way; however, the key structural factors that affect cooperation are not well understood. Moreover, the role structure plays with cooperation has largely been studied through observing overall cooperation rather than the underlying components that together shape cooperative behavior. In this paper we address these two problems by first applying evolutionary games to a wide range of networks, where agents play the Prisoner's Dilemma with a three-component stochastic strategy and then analyzing agent-based simulation results using principal component analysis. With these methods we study the evolution of trust, reciprocity and forgiveness as a function of several structural parameters. This work demonstrates that community structure, represented by network modularity, among all the tested structural parameters, has the most significant impact on the emergence of cooperative behavior, with forgiveness showing the largest sensitivity to community structure. We also show that increased community structure reduces the dispersion of trust and forgiveness, thereby reducing the network-level uncertainties for these two components; graph transitivity and degree also significantly influence the evolutionary dynamics of the population and the diversity of strategies at equilibrium.
A validated multi-channel electrochemical immunoassay for rapid fumonisin B1 determination in cereal samples
Authors: Ezquerra Alba , Vidal Juan C. , Bonel Laura , Castillo Juan R.
Published: April 2015

Fumonisin mycotoxins are natural contaminants of cereals mostly found in maize samples.
Two-dimensional electron gas and its electric control at the interface between ferroelectric and antiferromagnetic insulator studied from first principles
Authors: Borisov Vladislav , Ostanin Sergey , Mertig Ingrid
Published: April 2015

Using first-principles methods we demonstrate the possibility of using the ferroelectric polarization to create and control a two-dimensional electron gas at a multiferroic oxide interface.
Fast identification and quantification of BTEX coupling by Raman spectrometry and chemometrics
Authors: Moreau J. , Rinnert E.
Published: April 2015

Monoaromatic hydrocarbons (MAHs) monitoring is of environmental interest since these chemical pollutants are omnipresent.
Highly efficient quenching of tris(2,2′-bipyridyl)ruthenium(ii) electrochemiluminescence by ozone using formaldehyde, methylglyoxal, and glyoxalate as co-reactants and its application to ozone sensing
Authors: Gao Ying , Liu Xiaoyun , Qi Wenjing , Gao Wenyue , Li Yunhui , Xu Guobao
Published: April 2015

Ozone can dramatically quench tris(2,2′-bipyridyl)ruthenium(ii) ECL of formaldehyde, methylglyoxal, and glyoxalate, enabling highly sensitive ozone detection.
A double-enhanced strip biosensor for the rapid and ultrasensitive detection of protein biomarkers
Authors: Qin Chunyan , Wen Wei , Zhang Xiuhua , Gu Haoshuang , Wang Shengfu
Published: April 2015

A LFB based on AuNP aggregation and HRP-assisted dual-class signal amplification and the specific biotin–streptavidin recognition reaction.