bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep sequencing revealed molecular signature of horizontal gene transfer of plant like transcripts in the mosquito Anopheles culicifacies: an evolutionary puzzle
Authors: Sharma Punita , Das De Tanwee , Sharma Swati , Kumar Mishra Ashwani , Thomas Tina , Verma Sonia , Kumari Vandana , Lata Suman , Singh Namita , Valecha Neena , Chand Pandey Kailash , Dixit Rajnikant
Published: December 2015

In prokaryotes, horizontal gene transfer (HGT) has been regarded as an important evolutionary drive to acquire and retain beneficial genes for their survival in diverse ecologies. However, in eukaryotes, the functional role of HGTs remains questionable, although current genomic tools are providing increased evidence of acquisition of novel traits within non-mating metazoan species. Here, we provide another transcriptomic evidence for the acquisition of massive plant genes in the mosquito,Anopheles culicifacies. Our multiple experimental validations including genomic PCR, RT-PCR, real-time PCR, immuno-blotting and immuno-florescence microscopy, confirmed that plant like transcripts (PLTs) are of mosquito origin and may encode functional proteins. A comprehensive molecular analysis of the PLTs and ongoing metagenomic analysis of salivary microbiome provide initial clues that mosquitoes may have survival benefits through the acquisition of nuclear as well as chloroplast encoded plant genes. Our findings of PLTs further support the similar questionable observation of HGTs in other higher organisms, which is still a controversial and debatable issue in the community of evolutionists. We believe future understanding of the underlying mechanism of the feeding associated molecular responses may shed new insights in the functional role of PLTs in the mosquito.
Risk of intracranial hemorrhage in users of oral antithrombotic drugs: Study protocol for a nationwide study
Authors: Gulati Sasha , Solheim Ole , Carlsen Sven M. , Øie Lise R. , Jensberg Heidi , Gulati Agnete M. , Giannadakis Charalampis , Jakola Asgeir Store , Salvesen Øyvind
Published: December 2015

Background A wide range of antithrombotic medications can be used in the prevention and treatment of thrombosis. Among hemorrhagic complications of antithrombotic drugs, intracranial hemorrhage may have particularly devastating consequences with high morbidity, disability and mortality rates. The incidence and risks of intracranial hemorrhage in patients on antithrombotic treatments from regular clinical practice outside clinical trials remain largely unknown. It is not known if results from clinical trials can be extrapolated to everyday clinical practice. We will conduct a nationwide study to investigate the risks and incidence rates of intracranial hemorrhage in users oral antithrombotic drugs in Norway from 2008 through 2014. 

Methods and design The aim of this nationwide study is to investigate the incidence rates of intracranial hemorrhage requiring hospitalization in users of oral antithrombotic drugs. The study will be conducted within the approximately 4.7 million inhabitants of Norway from January 1st, 2008, to December 31st, 2014. Treatment and outcome data are obtained from the Norwegian patient registry and the Norwegian prescription database. 

Trial registration number Clinicaltrials.gov (NCT02481011)
CausalTrail: Testing hypothesis using causal Bayesian networks
Authors: Stöckel Daniel , Schmidt Florian , Trampert Patrick , Lenhof Hans-Peter
Published: December 2015

Summary Causal Bayesian Networks are a special class of Bayesian networks in which the hierarchy directly encodes the causal relationships between the variables. This allows to compute the effect of interventions, which are external changes to the system, caused by e.g. gene knockouts or an administered drug. Whereas numerous packages for constructing causal Bayesian networks are available, hardly any program targeted at downstream analysis exists. In this paper we present CausalTrail, a tool for performing reasoning on causal Bayesian networks using the do-calculus. CausalTrail's features include multiple data import methods, a flexible query language for formulating hypotheses, as well as an intuitive graphical user interface. The program is able to account for missing data and thus can be readily applied in multi-omics settings where it is common that not all measurements are performed for all samples.

Availability and Implementation CausalTrail is implemented in C++ using the Boost and Qt5 libraries. It can be obtained from https://github.com/dstoeckel/causaltrail
A Characterization of the SSD-Efficient Frontier of Portfolio Weights by Means of a Set of Mixed-Integer Linear Constraints
Authors: Longarela Iñaki R.
Published: December 2015

In this paper, the set of all second-order stochastic dominance (SSD)-efficient portfolios is characterized by using a series of mixed-integer linear constraints. Our derivation employs a combination of the first-order conditions of the utility maximization problem together with a judicious use of binary variables. This result opens the door to the formulation of optimizations whose objective function is free to select a particular portfolio out of the entire SSD-efficient set.

This paper was accepted by Jerome Detemple, finance.
OR Forum—An Algorithmic Approach to Linear Regression
Authors: Bertsimas Dimitris , King Angela
Published: December 2015

Linear regression models are traditionally built through trial and error to balance many competing goals such as predictive power, interpretability, significance, robustness to error in data, and sparsity, among others. This problem lends itself naturally to a mixed integer quadratic optimization (MIQO) approach but has not been modeled this way because of the belief in the statistics community that MIQO is intractable for large scale problems. However, in the last 25 years (1991–2015), algorithmic advances in integer optimization combined with hardware improvements have resulted in an astonishing 450 billion factor speedup in solving mixed integer optimization problems. We present an MIQO-based approach for designing high quality linear regression models that explicitly addresses various competing objectives and demonstrate the effectiveness of our approach on both real and synthetic data sets.
Joint Inventory and Markdown Management for Perishable Goods with Strategic Consumer Behavior
Authors: Hu Peng , Shum Stephen , Yu Man
Published: December 2015

In this paper we formulate and analyze a novel model on a firm’s dynamic inventory and markdown decisions for perishable goods. We consider a dynamic stochastic setting, where every period consists of two phases, clearance phase and regular-sales phase. In the clearance phase, the firm decides how much to order for regular sales, as well as whether to markdown some (or all) of the leftover inventory from the previous period that will be disposed otherwise. Since strategic consumers may buy the product during clearance sales for future consumption, markdown may cannibalize future sales at regular price. Hence, the firm needs to make a trade-off between product spoilage and intertemporal demand substitution. We show that the firm should either put all of the leftover inventory on discount or dispose all of it, and the choice depends on the amount of leftover inventory from the previous period. In particular, the firm should introduce markdown when the amount of leftover inventory is higher than a certain threshold, and dispose all otherwise. We also conduct numerical studies to further characterize the optimal policy, and to evaluate the loss of efficiency under static policies when compared to the optimal dynamic policy.
CROSSROADS—Strategy, Problems, and a Theory for the Firm
Authors: Felin Teppo , Zenger Todd R.
Published: December 2015

In this paper we develop the outlines of a theory for the firm—a theory that guides a firm’s path to value creation, in response to the critique by von Hippel and von Krogh [ von Hippel E, von Krogh G (2016) Identifying viable "need–solution pairs": Problem solving without problem formulation. Organ. Sci. 27:207–221; henceforth Hippel–Krogh] of the problem-solving perspective as a theory of value creation. Hippel–Krogh argue (a) that problems and solutions cannot always be separated because they often emerge as problem–solution or need–solution pairs that are discovered serendipitously, and (b) that deliberately formulating or choosing a single, fixed problem restricts the firm from accessing the vast array of external problem solvers and restricts the firm from valuable reformulations of the problem and “rich landscape search.” Although Hippel–Krogh raise interesting and important arguments, we claim that they miss what is most central about the problem-solving approach: the comparative, organizational, and strategic aspects of the theory. However, their critique is also important because it draws attention to a critical void in the problem-solving perspective, namely, the need for firms to possess a theory to guide their efforts at value creation.

We argue that this theory for the firm links problem solving with a broader theory of value creation, thus responding to the concerns raised by Hippel–Krogh. We discuss how firms theorize the process of value creation by articulating an overall architecture and bundle of problems around which each firm uniquely organizes and governs as a path to value creation. We provide two brief, informal examples (Starbucks and Apple) to illustrate our points, linking these examples to the need–solution landscape proposed by Hippel–Krogh. In all, we provide a broad sketch and outline of a theory of value creation as it relates to problem finding and problem solving while concurrently responding to points raised by Hippel–Krogh.
Dormancy as a Strategic Response to Detrimental Public Policy
Authors: Kozhikode Rajiv Krishnan
Published: December 2015

Organizations in democratic societies often encounter detrimental public policies that are later reversed through rather predictable political cycles. The standard organizational responses to detrimental public policies examined in the literature include exiting the market altogether, attempting to change the public policy through various political strategies, or passively complying with the policy. However, these responses might not be suitable when a detrimental policy is likely to be reversed. In this paper, I consider organizational dormancy, which entails a temporary reduction in an organization’s level of activity, as a viable alternative response. I propose that some organizations might be able to undergo a period of strategic inactivity in response to the onset of a detrimental public policy and maintain this inactivity until a favorable public policy returns. I also propose that such dormancy is rewarded when the favorable policy returns. An investigation of a panel of private commercial banks in the Indian banking industry from 1981 to 2004 lends support to this proposal.
Toward Organizational Pluralism: Institutional Intrapreneurship in Integrative Medicine
Authors: Heinze Kathryn L. , Weber Klaus
Published: December 2015

A critical stage in change toward institutional pluralism occurs when incumbent organizations must begin to integrate diverse logics in their operations. The required institutional work inside organizations at that stage—institutional intrapreneurship—involves distinctive challenges. Incumbent logics are entrenched in organizational routines, status orders, policies, and structures that hamper change and trigger resistance. We used qualitative data from two integrative medicine (IM) programs inside large healthcare organizations to understand how institutional intrapreneurs work to integrate the IM logic in these highly institutionalized organizations. We found that intrapreneurs use opportunistic tactics to create and strengthen organizational free spaces aligned with the new logic, and then leverage the capacity that is developed to extend elements of the new logic into the broader organization. This study suggests that a better understanding of the organizational context helps explain the fate of early-stage efforts toward institutional change.
User-Industry Spinouts: Downstream Industry Knowledge as a Source of New Firm Entry and Survival
Authors: Adams Pamela , Fontana Roberto , Malerba Franco
Published: December 2015

Recent scholarship on entrepreneurship suggests that the pre-entry know-how of start-ups, embodied in their founders, affects not only entry, but also performance. Although prior work focuses on new entrants from the focal industry (i.e., employee spinouts) and academic organizations (i.e., university spinoffs), this study identifies and examines a hybrid category of start-ups from downstream user-industries, which we call “user-industry spinouts.” We draw from the literature on evolutionary theory, user innovation, and industrial dynamics to propose that, given the unique combination of knowledge inherited by these entrants, their choices at entry and their ability to survive in the focal industry will differ with respect to other start-ups. We do this by extending existing work on new firm creation to investigate entry and performance in different product markets. Our findings, based on a dataset of start-ups in the semiconductor industry over a 10-year period (1997–2007), show that user-industry spinouts are more likely both to enter and to survive in market-specific product categories. We suggest that the pre-entry knowledge resources of spinouts may support entry and survival across industry boundaries. However, the specific nature of these resources will influence which product markets they choose to enter. Our results have theoretical implications for the literatures on entrepreneurship, industrial dynamics, and strategy.
Plasma Lipid Profiles of Transgenic mice expressing the Human ApoB100XCETP are altered differentially by Diets enriched with defined Fatty Acids
Authors: Hatahet Wael , Soofi Abdul , Ntekim Oyonumo , Fungwe Thomas
Published: December 2015

Dietary fat is known to modulate plasma lipid profiles. Synthesis of high density lipoproteins (HDL), which has protective effects on vascular disease is also influenced by dietary fats, but the mechanisms are unclear. The hapoB100XCETP transgenic mouse was used to investigate the effects of fatty acids on the metabolism of plasma lipoproteins, including the pathway leading to synthesis HDL. Male transgenic mice were fed with diets formulated to provide TG (33% energy) as tripalmitin (TP), triolein (TO), tristearin (TS) or equicaloric substitution of fat with carbohydrate (sucrose) for 4 weeks. Analysis of plasma profile showed that HDL-cholesterol were 53.7+14; 64.6+8.6; 50.2+3.3; 47.0+9.2 and 45.2+4.9 mg/dL for control, oleate, palmitate, stearate and sucrose based diets, respectively. LDL-cholesterol levels were 51.7+7.0; 23.1+7.0; 38.9+2.2; 75.1+1.8 and 46.8.1.0 mg/dl, for control, TO, TP, TS and sucrose, respectively. Hepatic Lecithin-cholesterol acyltransferase (LCAT) protein levels increased by 2-fold in mice fed TS or TO diets, compared to TP, while sucrose had no effect. The scavenger receptor class B type I (SR-B1) which plays an important role in meditating the uptake of HDL-derived cholesterol and cholesteryl ester in the liver and steroidogenic tissues increased in livers of animals fed TP and TO, while TS and sucrose did not have a similar effects. These results suggests that fatty acids can uniquely impact HDL, in addition, the ApoB100XCETP mouse is a useful model for the evaluation of how dietary components affect the risk of developing atherosclerosis and heart disease.
Storage Stability of Refined Oil From Lake Victoria Nile Perch (Lates Niliticus) Viscera
Authors: Okoth Michael , Aloo Joseph , Imungi Jasper
Published: December 2015

Nile perch (Lates niloticus) viscera oil was extracted by wet rendering method and refined by neutralization, deodorization and winterization. After winterization, the oil was decanted and separated by filtration into a low melting point fraction (LMPF) and a high melting point fraction (HMPF). The two fractions were used to carry out storage stability study. Each fraction was stored at room temperature (19 – 23oC) for a period of 20 weeks in transparent and amber colored glass containers. The oil fractions were subjected to quality tests to assess their storage stability. The effects of package color and storage duration were assessed by analyzing for the content of free fatty acids (FFA) as oleic acid and the peroxide value (PV) at the beginning of storage and at intervals of two weeks during storage. The resulting data were subjected to statistical analysis (p ≤ 0.05) using GenStat software, 13th edition. There was a general increase in FFA and PV, with significant differences between oil fractions and package color over storage time. For FFA, there was no interaction between the oil fraction and package color while for PV there was significant interaction between the oil fraction and package color. FFA increased from 0.26% to 0.59% for LMPF in clear package, 0.26 – 0.43% for LMPF in red package, 0.22 – 0.85% for HMPF in clear package, and 0.22 – 0.69% for HMPF in red package. PV increased from 0.50 mEq O2/kg oil to 11.65 mEq O2/kg oil for LMPF in clear package, from 0.5058 mEq O2/kg oil to 10.58 mEq O2/kg oil for LMPF in red package, from 1.01 mEq O2/kg oil to 9.94 mEq O2/kg oil for HMPF in clear package, after 20 weeks, and from 1.01 mEq O2/kg oil – 6.86 mEq O2/kg oil for HMPF in red package after 14 weeks. The levels of FFA and PV of LMPF in colored package remained within the CODEX limits of 0.3% and 5 mEq O2/kg oil respectively for refined fish oils up to 18 weeks. The FFA of HMPF surpassed the limit after 6 and 10 weeks for transparent and colored packages respectively. The FFA of LMPF in transparent package surpassed the limit after 8 weeks. Only low melting point oil fraction in transparent pack had PV above limit at 18 weeks. Results showed that colored package is more suitable for both oil fractions studied. In terms of FFA and PV, HMPF and LMPF can retain good quality at ambient temperatures for 10 and 18 weeks respectively.
Inflammation and Metabolic Syndrome: An Overview
Authors: Patel Hinal , Patel V. H
Published: December 2015

Inflammation is a reaction to a disrupted tissue homeostasis. Basically it is a tissue-destroying process that involves the recruitment of blood-derived products. Rapidly destroy or isolate the underlying source of the disturbance, removes damaged tissue and restore tissue homeostasis is the primary function of inflammation. Inflammatory and chronic metabolic alterations that together are termed metabolic syndrome. The risk of developing serious pathological conditions such as cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) is significantly associated with inflammation and its concurrent multi-organ abnormalities which represent a great burden upon societies, as they require significant resources from health care systems. Thus, understanding the tissue-specific pathogenic processes that lead to disease progression is required for the development of more effective therapeutic approaches.
Atmospheric Aerosols: Air Quality and Climate Change Perspectives
Authors: Manzoor Shabana , Kulshrestha Umesh
Published: December 2015

Recently, air quality has become a matter of concern of everyone. According to the reports, atmospheric aerosols play very crucial role in air quality. PM10 and PM2.5 aerosols are integral parts of total suspended particulate matter which affect our health. Often air quality has been reported very poor due to violation of National Ambient Air Quality Standard (NAAQS) limits. PM10 and PM2.5 limits are crossed for both residential as well as sensitive sites. This is one of the major reasons of increasing cases of respiratory diseases in urban areas. However, aerosol loadings alone are not the factor for deciding or predicting toxic and harmful effects of aerosols. Chemical composition and size ranges do matter. Aerosol loadings can be due to three major source categories viz. marine, crustal and anthropogenic. Since, marine and crustal content of aerosols are generally non-toxic and hence, degree of toxicity of air needs to be decided on the basis of anthropogenic fraction having metals, PAHs and other harmful content. Apart from air quality and health, atmospheric aerosols play vital role in other atmospheric processes such as cloud formation, radiative transfer and monsoon etc. Though there are several studies reported on different aspects of atmospheric aerosols, but most of the findings are sort of data reporting based on short term observations. Hence, there is need to investigate the atmospheric aerosols in order to demonstrate local and regional phenomenon on the basis of long term datasets.
Waste to Energy: A Green Paradigm in Solid Waste Management
Authors: Anis Mohamad , Siddiqui Tauseef
Published: December 2015

The current annual generation of municipal solid waste in India is estimated to be around 42 million tones which will rise rapidly with population growth, urbanization and improving living standards of people. The municipal solid waste (MSW) generation ranges from 0.25 to 0.66 kg/person/day with an average of 0.45 kg/person/day. In addition, large quantities of solid and liquid wastes are generated by industries. Most of the wastes generated find their way into land and water bodies. Without proper treatment, these wastes emit gases like Methane (CH4), Carbon Dioxide (CO2) etc, resulting in bad odor, emission of green house gases and increase in air and water pollution. This problem can be significantly mitigated through adoption of environment-friendly waste-to-energy technologies for the treatment and processing of wastes before disposal. It will not only reduce the quantity of wastes but also generate substantial quantity of energy. India at present is the world’s fifth biggest energy consumer and is predicted to surpass Japan and Russia to take the third place by 2030. Indian economy has shown a robust growth of around 8% in recent years and is trying to sustain this growth in order to reach goals of poverty alleviation. To achieve the required level of growth, India will need to at least triple its primary energy supply and quintuple its electrical capacity. This will force India, which already imports a majority of its oil, to look beyond its borders for energy resources. In India waste-to-energy has a potential of generating 1700 MW per person and this is scheduled to increase when more types of waste would be encompassed. At present hardly 50 MW power is being generated through waste-to-energy options. Waste combustion provides integrated solutions to the problems of the modern era by: recovering otherwise lost energy and thereby reducing our use of precious natural resources; by cutting down our emissions of greenhouse gases; and by both saving valuable land that would otherwise be destined to become landfill and recovering land once sacrificed to the products of consumerism. This paper focuses to present waste to energy as a green and sustainable solution of solid waste problem vis-à-vis its importance as renewable source of energy.
Rainfall Trend Analysis of Punjab, India Using Statistical Non-Parametric Test
Authors: Krishan Gopal , Chandniha Surendra , Lohani Anil
Published: December 2015

Annual, seasonal and monthly variations in rainfall trend in Punjab, India for 102 years (1901–2002) were analysed using statistical non-parametric tests - the Modified Mann-Kendall (MMK) test and Sen’s slope which indicated rising trend in rainfall in all the districts.
Development of an Overall Water Quality Index (OWQI) for Surface Water in Indian Context
Authors: Singh Surjeet , Ghosh N. C , Krishan Gopal , Galkate Ravi , Thomas T , Jaiswal R. K
Published: December 2015

A number of water quality indices based on classification criteria, sub-indices and aggregation function have been developed by the researchers for categorizing the water quality for different uses. In the present study, a general Overall Water Quality Index (OWQI) is developed to classify the surface water into five categories, viz. excellent, good, fair, poor and polluted. For this purpose, the concentration ranges have been defined on the basis of the Indian Standards (IS) and Central Pollution Control Board (CPCB) standards also taking into account other International standards of World Health Organization (WHO) and European Commission (EC). Sixteen parameters are selected based on social and environmental impact and weights are assigned on their relative importance to impact the quality of water. The proposed index improves understanding of water quality issues by integrating complex data and generates a score which describes the status of water quality. The proposed index will be very useful for the water management authorities to maintain good health of surface water resources.
Environmental and Landscapes Design in Archaeolandscapes by Using Remote Sensing
Authors: Samani Firoozeh , Bahrami Behrang
Published: December 2015

From the past, the combinations of the natural structures and the human features have created a specific cultural archaeolandscape. Therefore, the Environmental design in these landscapes have been presented through the main idea of “the passage of humans in the nature during over centuries” .In the new paradigm of integrated conservation in cultural landscapes, archaeological sites and buildings are evaluated in a wider range, and considerable attention is paid to them in the natural context. Recognizing the Connection between heritage and peoples over the time by focus on Environmental data integration, guide to find the destruction reasons and also guide us for best conservation. Therefore, archaeological sites, besides environmental factors, go under preservation and repair of the site and its environment. In this research, satellite data processing and image analysis have been applied besides environmental interpretations together with different scientific data. The result of these studies gave rise to comprehensive information to investigate and recognize the collocations of the ecological, archaeological and human structures from the past to the present and according to the purposes and strategies resulting from the wide environmental studies and the discussed principles of archaeolandscapes, attempts have been made to environmental design.
Water Quality Assessment Using Physico-Chemical Parameters and Heavy Metals of Gobind Sagar Lake, Himachal Pradesh (India)
Authors: Sharma Vandana , Walia Yogesh
Published: December 2015

Today the environment has become harmful for the health of living organisms due to excessive pollution and contamination of natural resources. The present investigation has been carried out with the objective to assess the water quality of the Gobind Sagar Lake, Bilaspur, Himachal Pradesh (India) using physico-chemical parameters with heavy metals of the lake. For this study, three sampling sites were identified and samples from different sites were collected in summer season and important parameters [Water Temperature, pH, Total Hardness, Dissolved Carbon Dioxide (CO2), Dissolved Oxygen (DO), Chemical Oxygen Demand (COD), Biological Oxygen Demand (BOD), Chloride, Total Alkalinity, Total Dissolved Solid (TDS)] with heavy metals [ Lead (P), Copper (Co), Iron (Fe), Cadmium (Cd), Nickel (Ni) and Manganese (Mn), Chromium (Cr) were analyzed. The results revealed that the different conditions of Gobind Sagar Lake in different sampling stations showed fluctuations in some physico-chemical parameters and also in heavy metals. These result depicted that water of lake was polluted in the form of nutrient enrichment which is due to agricultural activities and its runoff in and around catchment area of the lake. There are other many ways that things can end up in the lake as the free style way of disposal of industrial and domestic effluents etc. Results of studies on heavy metals in pollution are well documented revealing the toxic effects of these metals on aquatic organisms.
An Overview of Use of Linz-Donawitz (LD) Steel Slag in Agriculture
Authors: Chand Sasmita , Paul Biswajit , Kumar Manish
Published: December 2015

Slag generated from basic oxygen furnace (BOF) or Linz-Donawitz (LD) converter is one of the recyclable wastes in integrated steel plants. This paper deals with the present and possible use of LD slag in agriculture. At present, the amount of slag deposited in storage yard, leading to the occupation of farm land and serious pollution to the environment. Improving the slag utilization is an important way to resolve these problems. The physical and chemical characteristics of steel slag were analyzed and then the research progress of steel slag utilization in agriculture as fertilizer introduced. Due to increasing awareness of the environment, disposal, reuse of wastes without harming the environment has became a prime concern for the industry. The local availability of non conventional sources of plant nutrients and soil conditioners plays a vital role because of the non availability and higher price of environmental fertilizers. Therefore, this waste can be utilized for enhancing yield as well as solving the disposal problem and improve the environment.
Patient understanding and recall of risks and complications of dental implant treatment following informed consent
Authors: Esau Tim , Puryer James , McNally Lisa , O’Sullivan Dominic
Published: December 2015

When patients consent to undergo dental implant treatment, how much of the form do they really remember? Here, the recall and understanding of the risks and complications of dental implant treatment following a dental implant consent process is assessed.
Management of casualties in Misrata following the civil uprising in Libya, with an emphasis on maxillofacial injuries
Authors: Esmil Tarek , Breeze Johno , Sandhu Raj , Walton Gary
Published: December 2015

The Libyan city of Misrata was the focus of an intense period of fighting between government forces loyal to Gaddafi and rebels to the regime during the civil uprising in 2011. For a six-month period, the city was cut off from the outside world, apart from intermittent access from the sea, with limited medical facilities and staff to treat the growing number of casualties. Here, the background to the conflict, how the medical facilities were arranged in the city and the types of head, face and neck surgical procedures performed are described, alongside the lessons learned and suggestions for future conflicts.
Applications of MALDI Mass Spectrometry in Clinical Chemistry
Authors: Duncan Mark W , Nedelkov Dobrin , Walsh Ryan , Hattan Stephen J
Published: December 2015

BACKGROUND

MALDI-TOF mass spectrometry (MS) is set to make inroads into clinical chemistry because it offers advantages over other analytical platforms. These advantages include low acquisition and operating costs, ease of use, ruggedness, and high throughput. When coupled with innovative front-end strategies and applied to important clinical problems, it can deliver rapid, sensitive, and cost-effective assays.

CONTENT

This review describes the general principles of MALDI-TOF MS, highlights the unique features of the platform, and discusses some practical methods based upon it. There is substantial potential for MALDI-TOF MS to make further inroads into clinical chemistry because of the selectivity of mass detection and its ability to independently quantify proteoforms.

MALDI-TOF MS has already transformed the practice of clinical microbiology and this review illustrates how and why it is now set to play an increasingly important role in in vitro diagnostics in particular, and clinical chemistry in general.
Sulfatide Analysis by Mass Spectrometry for Screening of Metachromatic Leukodystrophy in Dried Blood and Urine Samples
Authors: Spacil Zdenek , Babu Kumar Arun , Liao Hsuan-Chieh , Auray-Blais Christiane , Stark Samantha , Suhr Teryn R , Scott C Ronald , Turecek Frantisek , Gelb Michael H
Published: December 2015

BACKGROUND

Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused by deficiency in arylsulfatase A activity, leading to accumulation of sulfatide substrates. Diagnostic and monitoring procedures include demonstration of reduced arylsulfatase A activity in peripheral blood leukocytes or detection of sulfatides in urine. However, the development of a screening test is challenging because of instability of the enzyme in dried blood spots (DBS), the widespread occurrence of pseudodeficiency alleles, and the lack of available urine samples from newborn screening programs.

METHODS

We measured individual sulfatide profiles in DBS and dried urine spots (DUS) from MLD patients with LC-MS/MS to identify markers with the discriminatory power to differentiate affected individuals from controls. We also developed a method for converting all sulfatide molecular species into a single species, allowing quantification in positive-ion mode upon derivatization.

RESULTS

In DBS from MLD patients, we found up to 23.2-fold and 5.1-fold differences in total sulfatide concentrations for early- and late-onset MLD, respectively, compared with controls and pseudodeficiencies. Corresponding DUS revealed up to 164-fold and 78-fold differences for early- and late-onset MLD patient samples compared with controls. The use of sulfatides converted to a single species simplified the analysis and increased detection sensitivity in positive-ion mode, providing a second option for sulfatide analysis.

CONCLUSIONS

This study of sulfatides in DBS and DUS suggests the feasibility of the mass spectrometry method for newborn screening of MLD and sets the stage for a larger-scale newborn screening pilot study.
Quantification of Anaplastic Lymphoma Kinase Protein Expression in Non–Small Cell Lung Cancer Tissues from Patients Treated with Crizotinib
Authors: Hembrough Todd , Liao Wei-Li , Hartley Christopher P , Ma Patrick C , Velcheti Vamsidhar , Lanigan Christopher , Thyparambil Sheeno , An Eunkyung , Monga Manish , Krizman David , Burrows Jon , Tafe Laura J
Published: December 2015

BACKGROUND

Crizotinib has antitumor activity in ALK (anaplastic lymphoma receptor tyrosine kinase)-rearranged non–small cell lung cancer (NSCLC). The current diagnostic test for ALK rearrangement is breakapart fluorescence in situ hybridization (FISH), but FISH has low throughput and is not always reflective of protein concentrations. The emergence of multiple clinically relevant biomarkers in NSCLC necessitates efficient testing of scarce tissue samples. We developed an anaplastic lymphoma kinase (ALK) protein assay that uses multiplexed selected reaction monitoring (SRM) to quantify absolute amounts of ALK in formalin-fixed paraffin-embedded (FFPE) tumor tissue.

METHODS

After validation in formalin-fixed cell lines, the SRM assay was used to quantify concentrations of ALK in 18 FFPE NSCLC samples that had been tested for ALK by FISH and immunohistochemistry. Results were correlated with patient response to crizotinib.

RESULTS

We detected ALK in 11 of 14 NSCLC samples with known ALK rearrangements by FISH. Absolute ALK concentrations correlated with clinical response in 5 of 8 patients treated with crizotinib. The SRM assay did not detect ALK in 3 FISH-positive patients who had not responded to crizotinib. In 1 of these cases, DNA sequencing revealed a point mutation that predicts a nonfunctional ALK fusion protein. The SRM assay did not detect ALK in any tumor tissue with a negative ALK status by FISH or immunohistochemistry.

CONCLUSIONS

ALK concentrations measured by SRM correlate with crizotinib response in NSCLC patients. The ALK SRM proteomic assay, which may be multiplexed with other clinically relevant proteins, allows for rapid identification of patients potentially eligible for targeted therapies.
Automated Multiplex LC-MS/MS Assay for Quantifying Serum Apolipoproteins A-I, B, C-I, C-II, C-III, and E with Qualitative Apolipoprotein E Phenotyping
Authors: van den Broek Irene , Romijn Fred P H T M , Nouta Jan , van der Laarse Arnoud , Drijfhout Jan W , Smit Nico P M , van der Burgt Yuri E M , Cobbaert Christa M
Published: December 2015

BACKGROUND

Direct and calculated measures of lipoprotein fractions for cardiovascular risk assessment suffer from analytical inaccuracy in certain dyslipidemic and pathological states, most commonly hypertriglyceridemia. LC-MS/MS has proven suitable for multiplexed quantification and phenotyping of apolipoproteins. We developed and provisionally validated an automated assay for quantification of apolipoprotein (apo) A-I, B, C-I, C-II, C-III, and E and simultaneous qualitative assessment of apoE phenotypes.

METHODS

We used 5 value-assigned human serum pools for external calibration. Serum proteins were denatured, reduced, and alkylated according to standard mass spectrometry–based proteomics procedures. After trypsin digestion, peptides were analyzed by LC-MS/MS. For each peptide, we measured 2 transitions. We compared LC-MS/MS results to those obtained by an immunoturbidimetric assay or ELISA.

RESULTS

Intraassay CVs were 2.3%–5.5%, and total CVs were 2.5%–5.9%. The LC-MS/MS assay correlated (R = 0.975–0.995) with immunoturbidimetric assays with Conformité Européenne marking for apoA-I, apoB, apoC-II, apoC-III, and apoE in normotriglyceridemic (n = 54) and hypertriglyceridemic (n = 46) sera. Results were interchangeable for apoA-I ≤3.0 g/L (Deming slope 1.014) and for apoB-100 ≤1.8 g/L (Deming slope 1.016) and were traceable to higher-order standards.

CONCLUSIONS

The multiplex format provides an opportunity for new diagnostic and pathophysiologic insights into types of dyslipidemia and allows a more personalized approach for diagnosis and treatment of lipid abnormalities.
MALDI-TOF-MS Assay to Detect the Hemizygous 22q11.2 Deletion in DNA from Dried Blood Spots
Authors: Kobrynski Lisa J , Yazdanpanah Golriz K , Koontz Deborah , Lee Francis K , Vogt Robert F
Published: December 2015

BACKGROUND

A hemizygous deletion of 1.5–3 Mb in 22q11.2 causes a distinct clinical syndrome with variable congenital defects. Current diagnostic methods use fluorescent in situ hybridization (FISH) or comparative genomic hybridization by microarray to detect the deletion. Neither method is suitable for newborn screening (NBS), since they cannot be performed on dried blood spots (DBS). We developed a MALDI-TOF-MS assay that uses DBS to measure the hemizygous deletion of UFD1L, located within the 22q11.2 region.

METHODS

We used DBS from 54 affected patients, previously tested by FISH or microarray, and 100 cord blood samples to evaluate the performance of the MALDI-TOF-MS assay. With a single primer pair, a 97-base oligonucleotide within UFD1L was amplified, as was a sequence on chromosome 18 that differs by 2 nucleotides. A multiplexed, single-base extension reaction created allele-specific products for MALDI-TOF-MS detection. The products were spotted onto a silicon chip, and the height of the spectral peaks identified the relative amounts of target and reference gene.

RESULTS

The median ratio of the spectral peak for each UFD1L target:reference base was 0.96 and 0.99 for controls, compared with 0.35 and 0.53 for 22q11 deletion syndrome patients. There was 100% concordance between FISH/microarray and MALDI-TOF-MS in all patients with 22q11.2 deletion syndrome.

CONCLUSIONS

This method can be reliably performed with DBS and is suitable for high sample throughput. This assay may be considered for use in population-based NBS for 22q11.2 deletion.
Recommendations for the Generation, Quantification, Storage, and Handling of Peptides Used for Mass Spectrometry–Based Assays
Authors: Hoofnagle Andrew N , Whiteaker Jeffrey R , Carr Steven A , Kuhn Eric , Liu Tao , Massoni Sam A , Thomas Stefani N , Townsend R Reid , Zimmerman Lisa J , Boja Emily , Chen Jing , Crimmins Daniel L , Davies Sherri R , Gao Yuqian , Hiltke Tara R , Ketchum Karen A , Kinsinger Christopher R , Mesri Mehdi , Meyer Matthew R , Qian Wei-Jun , Schoenherr Regine M , Scott Mitchell G , Shi Tujin , Whiteley Gordon R , Wrobel John A , Wu Chaochao , Ackermann Brad L , Aebersold Ruedi , Barnidge David R , Bunk David M , Clarke Nigel , Fishman Jordan B , Grant Russ P , Kusebauch Ulrike , Kushnir Mark M , Lowenthal Mark S , Moritz Robert L , Neubert Hendrik , Patterson Scott D , Rockwood Alan L , Rogers John , Singh Ravinder J , Van Eyk Jennifer E , Wong Steven H , Zhang Shucha , Chan Daniel W , Chen Xian , Ellis Matthew J , Liebler Daniel C , Rodland Karin D , Rodriguez Henry , Smith Richard D , Zhang Zhen , Zhang Hui , Paulovich Amanda G
Published: December 2015

BACKGROUND

For many years, basic and clinical researchers have taken advantage of the analytical sensitivity and specificity afforded by mass spectrometry in the measurement of proteins. Clinical laboratories are now beginning to deploy these work flows as well. For assays that use proteolysis to generate peptides for protein quantification and characterization, synthetic stable isotope–labeled internal standard peptides are of central importance. No general recommendations are currently available surrounding the use of peptides in protein mass spectrometric assays.

CONTENT

The Clinical Proteomic Tumor Analysis Consortium of the National Cancer Institute has collaborated with clinical laboratorians, peptide manufacturers, metrologists, representatives of the pharmaceutical industry, and other professionals to develop a consensus set of recommendations for peptide procurement, characterization, storage, and handling, as well as approaches to the interpretation of the data generated by mass spectrometric protein assays. Additionally, the importance of carefully characterized reference materials—in particular, peptide standards for the improved concordance of amino acid analysis methods across the industry—is highlighted. The alignment of practices around the use of peptides and the transparency of sample preparation protocols should allow for the harmonization of peptide and protein quantification in research and clinical care.
The power of photographs in the communication and public relations of tourist destinations and their brands through Facebook and Flickr
Authors: Míguez-González María Isabel , Huertas Assumpció
Published: December 2015

Social media, which are important tools of public relations, have revolutionized the communication of tourist destinations. Photographs are one of the elements that communications managers of destinations can use to communicate their brands. But how are these photographs used via social media? The results of this study show a more frequent use of photos on Facebook, whereas the use of photo-sharing sites such as Flickr is still not very widespread. Photos best communicate emotional values, but destinations most often use them to present their attraction factors. In addition, in many destinations there is a lack of communication strategy in the use of pictures, which complement information without regard for any actual communication criteria. The useful recommendations for destinations that can be drawn from the results are: a more strategic use of photographs in communication via social media and the utilization of their potential in communicating the brand’s emotional values.
East European think tanks in social media – towards the model of evaluation of effective communication/PR strategies: Case study analysis
Authors: Castillo-Esparcia Antonio , Almansa-Martínez Ana , Smolak-Lozano Emilia
Published: December 2015

Taking into account the recent development of social media and its impact on PR practice among different organizations, this study aims to examine and assess the performance of PR practice think tanks in social media. The major focus is on social media application to their PR strategies and general output and outcomes of this implementation. The study is based on a case study method combined with triangulated techniques of data analysis and collection. The sample is formed by the selected East European think tanks. The study applies free of charge eTools for digital communication measurement in order to detect the value of the presence and activity in various social networks. The objective of the study is to examine whether East European think tanks apply 2.0 communication and to determine the best practices with their corresponding values in order to present a benchmark for such organiza- tions in this area of digital space.
Som la Pera: How to develop a social marketing and public relations campaign to prevent obesity among teenagers in Catalonia
Authors: Lozano Natàlia , Prades Jordi , Montagut Marta
Published: December 2015

Som la Pera is a public communication campaign for the prevention of obesity and the promotion of healthy lifestyles among teenagers, launched in May 2014 in Reus (Catalonia, Spain). The campaign is linked to the EU-funded project EYTO, and establishes consistent bridges between public relations and social marketing. This article argues that although these fields have traditionally been wary of each other, both have complementary aspects such as interventions that encourage behavioural changes regarding sociocultural contexts. These contact points especially occur in health promotion campaigns.
Grappling with inclusion: Ethnocultural diversity and socio-musical experiences in Common Thread Community Chorus of Toronto
Authors: Yerichuk Deanna
Published: December 2015

This pilot research study explored ethnocultural backgrounds of choristers and their socio-musical experiences participating in Common Thread Community Chorus of Toronto, a community choir that actively pursues cultural inclusion through policies of musical and financial accessibility, as well as choosing repertoire of diverse cultures. A survey of choristers investigated how Common Thread members’ ethnocultural backgrounds informed their perceptions of their musical and social experiences and of the choir’s cultural diversity, working from the assumption that all people have ethnocultural backgrounds. Research findings reveal complex and diverse cultures when singers reflect on their own experiences, but choristers tended to reduce cultural diversity to race and language when thinking about the choir as a whole, suggesting that perceptions may be operating from a white normative centre. The results of this pilot research raise significant questions about multicultural education and cultural inclusion efforts within community choral practices in ethnically diverse urban environments.
‘This Is My Truth, Now Tell Me Yours’: Emphasizing dialogue within Participatory Music
Authors: Camlin David A.
Published: December 2015

As a group, musicians have traditionally been resistant to conceptualizing their educational practice in participatory settings. Rather than continuing to strive for an elusive consensus, this article suggests we would do better to see our work in a different way, using the concept of dialogue to enable all of the diverse perspectives on music educational practice to have validity, as well as giving us insights into the kinds of teaching and learning exchanges that go on in Participatory Music. In particular, the concept of dialogue invites us to re-appraise some of the traditional dichotomies associated with music and music education – e.g. access/excellence, process/product, ethical/technical – so that they too can be seen as positions that ‘widen dialogic space’.