bluuebunny/crossref_metadata_2025 huggingface dataset:
Price Adjustment in Currency Unions: Another Dimension to the Endogeneity of the Optimum Currency Area Criteria?
Authors: Bleaney Michael , Yin Lin
Published: January 2018

In a rational expectations model, wages and prices should respond more to shocks in currency unions than under adjustable pegs because of the absence of exchange rate adjustment. This is an aspect of the endogeneity of the optimum currency area criteria that has been largely ignored. Empirical evidence from three currency unions tends to suggest some degree of endogeneity of price flexibility, but the rate of adjustment is slow. Self‐selection into currency unions by countries with naturally greater price flexibility does not appear to be a significant factor.
Obesity class does not further stratify outcome in overweight and obese pediatric patients after heart transplantation
Authors: Ryan Thomas D. , Zafar Farhan , Siegel Robert M. , Villa Chet R. , Bryant Roosevelt , Chin Clifford
Published: January 2018

The effect of obesity stratification on pediatric heart transplant outcomes is unknown. The UNOS database was queried for patients ≥2‐<18 years listed for heart transplant and stratified by BMI: normal (BMI>5%‐≤85 percentile), overweight (BMI=86%‐95 percentile), class 1 (BMI=100%‐120% of 95 percentile), class 2 (BMI=121%‐140% of 95 percentile), and class 3 obesity (BMI>140% of 95 percentile). A total of 5056 individuals were listed for transplant, with 71% normal, 13% overweight, 10% class 1, 4% class 2, and 2% class 3 obesity. Waitlist survival was not different between groups. Post‐transplant survival was decreased in overweight and combined obese groups vs normal, with no further difference between overweight and obese classes. Overweight and obese patients had higher listing status and were more likely to have ventilator, inotrope, and mechanical circulatory support at listing. After transplant, there was an association of overweight‐obese patients with diabetes and rejection requiring hospitalization. Stricter definition of normal weight reveals overweight‐obese status was an independent risk factor for poorer post‐transplant survival, without further effect by stratification of weight class. However, because there is no difference in waitlist survival, this study does not allow the selection of absolute weight‐based criteria regarding transplant listing and suggests the need to look further for modifiable risk factors post‐transplant.
Food Ethics II: Consumption and obesity
Authors: Barnhill Anne , Doggett Tyler
Published: January 2018

This article surveys recent work on some issues in the ethics of food consumption. It is a companion to our piece on food justice and the ethics of food production.
Why do older people refuse resuscitation? A qualitative study examining retirement village residents’ resuscitation decisions
Authors: Ramages Meagan , Cheung Gary
Published: January 2018

Background

There is a dearth of qualitative research on resuscitation preferences of older New Zealanders. The aim of this study was to investigate the resuscitation preferences of older New Zealanders in a retirement village or residential care setting, as well as the reasons for these preferences.

Methods

This study had 37 participants from two retirement villages in Auckland, New Zealand. Participants were interviewed about a hypothetical case vignette about cardiopulmonary resuscitation, and then they completed a semi‐structured interview. Interviews were subsequently transcribed and analyzed by two independent researchers using thematic qualitative methodology.

Results

The majority of the participants (n = 25, 67.6%) decided against resuscitation, 10 (27.0%) wanted resuscitation, and 2 (5.4%) were ambivalent about their resuscitation preferences. Three main themes emerged during the data analysis regarding participants’ reasons for deciding against resuscitation: (i) the wish for a natural death; (ii) advanced age; and (iii) a realistic awareness about the consequences of resuscitation. Responses related to the third these had three subthemes: (i) reduced quality of life; (ii) loss of personal integrity and sense of existence; and (iii) concern that resuscitation could result in unnecessary costs or a burden on others. Among participants who preferred resuscitation, two main themes emerged regarding their reasons for wanting resuscitation: (i) the wish to prolong a good quality of life; and (ii) unrealistic expectations of resuscitation.

Conclusions

Older people in this study were able to make reasoned decisions about resuscitation based on balancing their subjective estimations of quality of life and the presumed consequences of resuscitation. It is important therefore to educate older adults about the potential outcomes of resuscitation and explore (and document) their reasoning when discussing resuscitation preferences so their wishes can be respected.
A Comprehensive Risk Analysis of Transportation Networks Affected by Rainfall‐Induced Multihazards
Authors: Liu Kai , Wang Ming , Cao Yinxue , Zhu Weihua , Wu Jinshan , Yan Xiaoyong
Published: January 2018

Climate change and its projected natural hazards have an adverse impact on the functionality and operation of transportation infrastructure systems. This study presents a comprehensive framework to analyze the risk to transportation infrastructure networks that are affected by natural hazards. The proposed risk analysis method considers both the failure probability of infrastructure components and the expected infrastructure network efficiency and capacity loss due to component failure. This comprehensive approach facilitates the identification of high‐risk network links in terms of not only their susceptibility to natural hazards but also their overall impact on the network. The Chinese national rail system and its exposure to rainfall‐related multihazards are used as a case study. The importance of various links is comprehensively assessed from the perspectives of topological, efficiency, and capacity criticality. Risk maps of the national railway system are generated, which can guide decisive action regarding investments in preventative and adaptive measures to reduce risk.
Parental incarceration and child outcomes: Those at risk, evidence of impacts, methodological insights, and areas of future work
Authors: Haskins Anna R. , Amorim Mariana , Mingo Meaghan
Published: January 2018

The past 15 years of sociological scholarship assessing the intergenerational consequences of parental incarceration has produced a large body of work suggesting, on the aggregate, detrimental impacts on behavioral, educational, and health outcomes for American children. In this review, we briefly outline who is most at risk for experiencing parental incarceration, before providing an overview of recent multidisciplinary research on the impacts of parental incarceration for American children, ages 0–17. While our review centers on research within the discipline of sociology, we also highlight the interdisciplinary nature and methodological range of work in this subfield in order to provide a more holistic picture of the breadth and variation in impacts of this uniquely American phenomenon. Finally, we conclude with a discussion of the gaps in current literature and areas ripe for further development. In particular, we note future sociological work aimed at exploring mechanisms, addressing heterogeneity in effects, and highlighting pathways for resilience in children of the incarcerated is much needed in order to further develop our understanding of the broader intergenerational consequences of America's experiment in mass incarceration.
Spontaneous preterm birth prevention in multiple pregnancy
Authors: Murray Sarah R , Stock Sarah J , Cowan Shona , Cooper Elizabeth Sarah , Norman Jane E
Published: January 2018

Key content

Twin pregnancies are associated with a three‐fold greater perinatal mortality than singleton pregnancies. Prematurity is a main contributor, with 50% of twin pregnancies delivering before 37 weeks and 10% delivering before 32 weeks of gestation.

The aetiology of preterm delivery in twin pregnancies is likely multifactorial and different from that of singletons.

Cervical cerclage reduces preterm birth rates in singletons but has mixed results in twins with some studies showing harm.

The use of progesterone to prevent preterm birth in singletons has conflicting results and has not been proven to prevent preterm birth in twins. Studies continue to determine whether the cervical pessary is effective in preventing preterm birth in multiple pregnancies.

There is a paucity of data available on the prevention of preterm birth in triplets/higher order multiples but similar principles to twin pregnancy apply.

Learning objectives

To review the burden of preterm birth in multiple pregnancy.

To understand the methods available for preventing preterm birth in multiple pregnancies and the evidence surrounding the use of each one.

To be aware of the use of the Arabin pessary.
Preanalytical validation of an in‐house radioimmunoassay for measuring calprotectin in feline specimens
Authors: Heilmann Romy M. , Grützner Niels , Handl Stefanie , Suchodolski Jan S. , Steiner Jörg M.
Published: January 2018

Background

Calprotectin is a marker of inflammatory disorders in people, and serum and fecal calprotectin were shown to be increased in dogs with gastrointestinal inflammation. Biomarkers of gastrointestinal inflammation are currently lacking in cats.

Objectives

The purpose of the study was to analytically validate the canine calprotectin radioimmunoassay for quantification of calprotectin in feline specimens.

Methods

The immunoassay was analytically validated by determining assay working range, dilutional parallelism, spiking recovery, and intra‐ and inter‐assay variability. Reference intervals for fecal calprotectin were established from healthy cats, and the influence of age, sex, and housing condition on fecal calprotectin was determined.

Results

The working range of the assay was 1.5–346.2 μg/g of feces and 11.2–8654.4 μg/L of serum. Observed‐to‐expected ratios (O/E) for serial dilutions of fecal extracts ranged from 77.3% to 112.0% (mean: 99.2%) and from 95.7% to 161.4% (mean: 118.5%) for spiking recovery. Intra‐ and inter‐assay coefficients of variation for fecal samples were ≤ 11.0% and ≤ 12.8%, respectively. Fecal calprotectin concentrations ranged 1.5–66.5 μg/g (3‐day sample mean) and 1.5–126.1 μg/g (3‐day sample maximum). Housing conditions, sex, or age did not affect fecal calprotectin (all P > .05). For serial dilutions of serum samples, O/E ranged from 96.0% to 152.0% (mean: 115.7%). Serum calprotectin concentrations in healthy cats ranged from 108.8 to 255.3 μg/L (median: 158.2 μg/L).

Conclusions

The canine radioimmunoassay for the measurement of calprotectin is analytically sensitive, linear, reproducible, accurate, and sufficiently precise (CVA ≤ 43.2%) for use with feline feces (with a loss of accuracy at high calprotectin concentrations). The RIs for feline fecal calprotectin are comparable to those established for dogs. Independence of fecal calprotectin from age and sex agrees with findings in dogs.
Evaluation of a laparoscopically assisted ovariectomy technique in cats
Authors: Sakals Sherisse A. , Rawlings Clarence A. , Laity Jamie , Hofmeister Erik H. , Radlinsky MaryAnn G.
Published: January 2018

Objective

To describe a laparoscopically assisted ovariectomy (LAO) technique in the cat with a bipolar vessel sealing device (BVSD) or suture ligation and to compare the outcomes to open ovariohysterectomy (OO).

Study Design

Randomized prospective study

Animals

Healthy, adult, sexually intact female cats (n = 30).

Methods

Ten cats were assigned to each group: LAO with BVSD (group A), LAO with ligation (group B), and OO with ligation (group C). Surgical times and complications were assessed. Serum glucose and cortisol were measured prior to surgery and at 1, 2, 4, 6, 12, and 24 hours after surgery. Pain was scored by using an interactive visual analog scale (IVAS) at 0, 1, 2, 4, 6, 8, 12, 18, 24, 36, and 48 hours after surgery. Rescue analgesia was provided when IVAS score was 4 or more. Physiological and serum values and IVAS scores were compared among groups with area under the curve (AUC) by using a 1‐way ANOVA.

Results

Surgical time was shortest for group C (19.1 ± 5.2 minutes;P < .0002); there was no significant difference between groups A (27.7 ± 6.6 minutes) and B (33.2 ± 8.2 minutes). All procedures were completed successfully. No significant differences among groups were found in IVAS scores (P = .36), rescue analgesia (P = .22), glucose AUC (P = .53), or cortisol AUC (P = .27).

Conclusion

The LAO technique was accomplished as described in all cats with no complications or failures. Pain scores were not different from cats undergoing OO. LAO can be performed efficiently to maximize the benefits of minimally invasive surgery and is amenable to clinical practice.
A Cross-Cultural Investigation of Gender-Bound Language Use in Turkish and English Plays: Implications for Foreign Language Education
Authors: Genc Zubeyde Sinem , Armagan Kıymet Selin
Published: January 2018

The aim of the study is to investigate gender-bound language use in Turkish and English languages and to identify the differences and similarities across cultures and genders in the plays with family and social themes. Four English and five Turkish plays were chosen randomly for comparison. The number of words in the plays were taken into consideration for an accurate and balanced analysis. For this reason, the closeness of the number of words used by male and female characters in the plays were more important than the number of plays in total. The Turkish plays consisted of 6781 words and the English plays comprised 7091 words. Thus, in the plays considered as samples of language, a total of 13.872 words were studied with respect to the use of intensifiers, hedges and tag questions in two major groups: (1) cross gender & same culture, (2) same gender & cross culture, within the framework of Lakoff’s (1975) proposal concerning linguistic differences between males and females. A Pearson chi-square test was conducted on the quantitative data for all the analyses. The findings of the study showed that there were significant differences only in the use of hedges. No significant differences in the use of intensifiers and tag questions within the corpus under investigation were observed between the groups. This cross-cultural comparison on English and Turkish implies that Lakoff’s proposition regarding gender-bound language use needs further exploration. The study sheds light upon intercultural communication, and raises awareness and understanding of whether and how language use differs between different genders and cultures, which might be helpful for teachers and learners during the processes of teaching and learning English or Turkish as a foreign language. Furthermore, when the results of the study are considered from the point of intercultural communication, this investigation unveils the similarities and differences between English and Turkish languages in terms of use of intensifiers, hedges, and tag questions.
Electronic Slideshow Presentations in the Higher Education Teaching and Learning Process
Authors: Ferreira Carlos Miguel , Santos Ana Isabel , Serpa Sandro
Published: January 2018

The use of electronic slide presentations (ESP), usually through PowerPoint or Prezi software, has become widespread in higher education and is part of the expectations and perceptions of both teachers and students of how a successful and quality class should be. Is this dissemination of ESP use justified by the pedagogical quality fostered in learning? While its use can help focus attention on the content of the subject during classes, there are also limitations in this process, both in the dimension of teaching, by the teacher, and in the dimension of learning, by the student. This paper seeks to provide a contribution to the debate on this topic, and the advantages and limitations in using ESP. It is concluded that there is a need, on the one hand, to define the use of ESP, by assaying their application, as well as, on the other hand, to simultaneously develop other pedagogical ways of teaching, whose articulation can make the student’s role more active and pertinent, and enable the feedback to the student on the part of the teacher, so that it may be possible to regulate the teaching and learning process in a timely manner.
The Lack of Interdisciplinarity in Undergraduate Geography Teaching in Turkey
Authors: Bilgili Münür
Published: January 2018

The aim of this study is to understand and explore interdisciplinarity in geography and undergraduate geography courses in geography teaching departments in Turkey. There is a growing literature in science underscoring the importance of interdisciplinary approach and its beneficial outcomes. Increasing body of knowledge on social theory, on philosophical and theoretical movements and paradigms have made easier communication among disciplines which give rise to more perceptible interdisciplinarity specifically in social sciences and humanities.At the second part of the present study we focused on relationships between geography courses, interdisciplinary approach and course selection. Because in the study course selection is seen as the most important point to analyze and understand the extent to which whether interdisciplinarity finds a place in geography teaching. Lastly, it is given some conclusions by making suggestions.
Building Automation and the Contextualization of Information Technology: The Journey of a Midwestern Community College in the U.S.
Authors: Grandgenett Neal , Perry Pam , Pensabene Thomas , Wegner Karen , Nirenberg Robert , Pilcher Phil , Otterpohl Candi
Published: January 2018

The buildings in which people work, live, and spend their leisure time are increasingly embedded with sophisticated information technology (IT). This article describes the approach of Metropolitan Community College (MCC) in Omaha, Nebraska of the United States to provide an occupational context to some of their IT coursework by organizing IT instruction around the context of building automation systems (BAS). This contextualization allows IT students not only to study IT as a standalone discipline but also to study its integrated use within a specific occupational context. The article also describes MCC’s focused curriculum design efforts funded by the National Science Foundation’s Advanced Technological Education program. These efforts toward BAS-contextualization of the IT curriculum have become a catalyst for systematic contextualization of IT instruction at MCC and support the institution’s broader efforts to become a national model in IT instruction and interdisciplinary engagement within the United States. The research-based approach, activities, and outcomes of this project are all described here, as well as the lessons learned by one community college seeking to make their IT program increasingly relevant to their students and the IT workforce of today.
Role of the carotid body chemoreceptors in glucose homeostasis and thermoregulation in humans
Authors: Joyner Michael J. , Limberg Jacqueline K. , Wehrwein Erica A. , Johnson Blair D.
Published: January 2018

The carotid bodies (CBs) are multi‐modal sensory organs located bilaterally at the bifurcation of the carotid artery and innervated by the carotid sinus nerve (Hering's nerve), a branch of the IX cranial nerve. While the CBs (or embryologically analogous structures) are well known as the dominant oxygen‐sensing organ in vertebrates, in mammals there is evidence that the CBs may also sense glucose and temperature, and respond to circulating hormones and other factors. Additionally, the CBs likely participate in regulating baseline levels of sympathetic tone. In this brief review, we focus on the evolution of our efforts to understand ‘what else’ beyond oxygen sensing the CBs do in humans.

image
Equivalent Stiffness Model of a Proton Exchange Membrane Fuel Cell Stack Including Hygrothermal Effects and Dimensional Tolerances
Authors: Fly Ashley , Chen Rui , Wang Xiaodong
Published: January 2018

Proton exchange membrane fuel cells (PEMFCs) require mechanical compression to ensure structural integrity, prevent leakage, and to minimize the electrical contact resistance. The mechanical properties and dimensions of the fuel cell vary during assembly due to manufacturing tolerances and during operation due to both temperature and humidity. Variation in stack compression affects the interfacial contact pressures between components and hence fuel cell performance. This paper presents a one-dimensional equivalent stiffness model of a PEMFC stack capable of predicting independent membrane and gasket contact pressures for an applied external load. The model accounts for nonlinear component compression behavior, thickness variation due to manufacturing tolerances, thermal expansion, membrane expansion due to water uptake, and stack dimensional change due to clamping mechanism stiffness. The equivalent stiffness model is compared to a three-dimensional (3D) finite element model, showing good agreement for multicell stacks. Results demonstrate that the correct specification of gasket thickness and stiffness is essential in ensuring a predictable membrane contact pressure, adequate sealing, and avoiding excessive stresses in the bi-polar plate (BPP). Increase in membrane contact pressure due to membrane water uptake is shown to be significantly greater than the increase due to component thermal expansion in the PEMFC operating range. The predicted increase in membrane contact pressure due to thermal and hydration effects is 18% for a stack containing fully hydrated Nafion® 117 membranes at 80 °C, 90% relative humidity (RH) using an eight bolt clamping design and a nominal 1.2 MPa assembly pressure.
The Use and Results of the Wind Machine to Prevent Freeze Damage
Authors: Georg James G.
Published: January 2018

The Federal-State Frost Warning Service, Lakeland, Florida has been investigating the use of wind machines for frost protection under Florida weather conditions for the past six years. Lake Garfield Nurseries Company of Bartow was the cooperator during all the investigations to date. Their machines were located in nursery and small tree plots, and the effectiveness of the machines on the 18" temperature profile was our primary concern. More recently, however, studies at standard shelter height have also been made in a bearing grapefruit grove. A summary of most investigations is available upon request from the Federal-State Frost Warning Service, Box 1058, Lakeland, Florida.

Paper published with permission.
Fundamentals of Fluid Flow Applicable to the Citrus Industry
Authors: Farber Erich A.
Published: January 2018

Many technical processes such as the ones found in the Citrus Industry involve the flow of fluids. The flow of these fluids must be closely controlled to achieve the desired results. To be able to do this it is essential to understand the characteristics of the flowing fluids and to recognize the basic laws of nature governing this flow. With this information and knowledge it is then possible to accomplish the objectives with nature helping the process.

Paper published with permission.
Interpretation of Present Florida Pollution Control Regulations
Authors: Nielsen A. T.
Published: January 2018

Traditionally handled at state and local levels, pollution of waters is, in effect, now largely directed by the Federal government. However, the Federal administrators are seeking the joint involvement of State governments in controlling pollution through the device of State laws and river compacts — the latter; of course, applying to river basins involving several States or where States have a mutual boundary in a river. The chronology of the Federal legislation starts with the Water Pollution Control Act of 1948. It was limited in scope when it was fully implemented, and the government’s real role was still confined by the Rivers and Harbors Act of 1899, the Public Health Service Act of 1912, and the Oil Pollution Control Act of 1924. The amendments to the Federal Water Pollution Control Act of 1956 established a basic policy that water pollution problems are best solved at the local level. Grants were made to States and interstate agencies for water pollution control activities and grants for waste treatment plant construction. Purposes were limited and a complicated system of Federal controls resulted. The Act was further amended in 1961 to extend Federal pollution abatement authority to all interstate and navigable waters in construction grants and encouraged the research activity.

Paper published with permission.
A Basic View of Solid State Electronics
Authors: Mathews Bruce E.
Published: January 2018

Solid State Electronics includes the study and development of a large class of devices which are replacing vacuum tube techniques and revolutionizing the applications of electrical engineering. The most famous member of this new family of devices is the transistor. All of us are influenced by these developments right in our homes since all modern radio and television sets use the transistor as a basic element. The success of our space effort is largely due to the advances in solid state electronics. Virtually all industries, including the citrus industry, have felt the impact of these developments in making available whole new concepts in instrumentation, control devices, and computers. The future possibilities are unlimited. Already we are seeing the expression of solid state electronics in a whole new concept of design and manufacture called microelectronics. Although one does not need to understand the theory of solid state electronics to enjoy the fruits of the developments, I thought it would be interesting to you to have a brief basic view of a subject which is having a significant impact on the citrus industry.

Paper published with permission.
Considerations for Air Power Systems
Authors: Johnson Robert S.
Published: January 2018

The availability of compressed air in plants today is viewed by many as being in the same category with electricity, water and gas. The one major difference, however, lies in the fact that for most industrial plants compressed air is generated within the plant proper and the compressor and related equipment is maintained by “In-Plant Personnel”, while electricity and its related generating equipment and clean water and its related purification and pumping equipment are supplied from outside facilities and maintained by others. The difference thusly becomes clear. In the case of compressed air, the air compressor and related accessories represent a capital investment on the part of the user, while the other services (electricity, water, gas, etc.) are essentially services paid for on a usage basis and charged as a monthly cost of operation. Although there is a difference as to the source of the utility, compressed air being considered as such is expected to be every bit available in sufficient capacity and pressure by plant management as are ampers and voltage in the case of electrical power or gallons of pure pressurized water. This difference requires the watchful eye of plant management and maintenance personnel, for, unlike the other utilities, the compressed air source and usage is their complete responsibility and not that of the local utilities.

Paper published with permission.
Is Your Evaporator Polluting?
Authors: Rebeck Harold M.
Published: January 2018

We in the citrus processing industry have been contributing to the pollution of Florida lakes and streams, air and land for a number of years. Now, as just about everyone knows it is beginning to catch-up with us, and indeed its a problem all over the world where any food or chemical processing takes place. Some of us have already made the local newspapers and we will all probably make the national news before we get the problem solved.

Paper published with permission.
Protecting Floors in Citrus Plants
Authors: Wasser John
Published: January 2018

Concrete floors in food processing plants require protection from excessive abrasive and corrosive exposures. Failure to provide it results in early floor deterioration. The development, use and effectiveness of materials designed to protect concrete play a key role in lengthening the useful life of plant floors. The substances include structural materials, coating and overlayments.

Paper published with permission.
In situ cationization of molecular ions sputtered from organic specimens under cluster bombardment
Authors: Gnaser Hubert , Bock Wolfgang , Matsuo Jiro
Published: January 2018

In an attempt to investigate the possibility of an in situ cationization of molecular ions in time-of-flight secondary ion mass spectrometry, low-energy 500 eV Cs+ ions were implanted in organic materials before their analysis by Bi3+ cluster bombardment. Specifically, three different organic samples were used: arginine, leu-enkephalin, and polyethylene glycol (both in a pure state and as a mixture with Na trifluoroacetic acid). For the pristine specimens, characteristic secondary ion species were typically observed: (M+H)+ in the case of arginine and leu-enkephalin, whereas for polyethylene glycol Na-cationized oligomer ions were detected with masses up to ∼3000 u. Cs+ was implanted into these samples with fluences ranging from 2 × 1012 to 8 × 1013 cm–2. Already for the lowest implantation fluence, a substantial signal of Cs+ secondary ions was observed in the sputtered flux; it seems to saturate at about 1 × 1013 Cs+ cm−2. On the other hand, with increasing Cs incorporation, molecular secondary ions containing Cs were found for arginine and leu-enkephalin, notably (M+Cs)+, albeit with low intensities. Concurrently, a decrease of the intensities of (M+H)+ ions was noted. By contrast, for polyethylene glycol, no Cs-adduct ions were observed, neither for the pure nor for the mixed specimens. Furthermore, the implantation of Cs has little influence on the ion emission from these samples. The results seem to indicate that for the applied bombardment conditions Cs+ cationization has a rather limited efficiency.
Generalized method for probing ideal initial polarization states in multibeam Lloyd's mirror interference lithography of 2D scale gratings
Authors: Chen Xiuguo , Shimizu Yuki , Chen Chong , Chen Yuan-Liu , Gao Wei
Published: January 2018

Delicate control of the initial polarization states of sub-beams incident to the interferometer unit in multibeam Lloyd's mirror interference lithography is of great significance for the fabrication of high-precision two-dimensional (2D) scale gratings. In this work, the optimization of the initial polarization states of incident sub-beams is formulated as a constrained multiobjective optimization problem. A generalized method that allows the incident sub-beams to initially have the general elliptical polarization states in the optimization is proposed based on the multiobjective genetic algorithm. It is demonstrated that the method is capable of delivering ideal initial polarization states with which the cross-interference between the two once-reflected sub-beams on the grating substrate of the interferometer unit can be completely eliminated from the resultant 2D interference fringes. The feasibility of the proposed method is verified through the comparison between the simulated 2D interference fringes and the fabricated 2D scale gratings under the achieved ideal initial polarization states.
Complete enzyme set for chlorophyll biosynthesis in
Escherichia coli
Authors: Chen Guangyu E. , Canniffe Daniel P. , Barnett Samuel F. H. , Hollingshead Sarah , Brindley Amanda A. , Vasilev Cvetelin , Bryant Donald A. , Hunter C. Neil
Published: January 2018

Escherichia coli
has been engineered to produce chlorophyll.
TLR7
escapes X chromosome inactivation in immune cells
Authors: Souyris Mélanie , Cenac Claire , Azar Pascal , Daviaud Danièle , Canivet Astrid , Grunenwald Solange , Pienkowski Catherine , Chaumeil Julie , Mejía José E. , Guéry Jean-Charles
Published: January 2018

Biallelic
TLR7
expression in immune cells may contribute to increased autoimmune disease risk in women.
Azithromycin Resistance in Shigella spp. in Southeast Asia
Authors: Darton Thomas C. , Tuyen Ha Thanh , The Hao Chung , Newton Paul N. , Dance David A. B. , Phetsouvanh Rattanaphone , Davong Viengmon , Campbell James I. , Hoang Nguyen Van Minh , Thwaites Guy E. , Parry Christopher M. , Thanh Duy Pham , Baker Stephen
Published: January 2018

Infection by
Shigella
spp. is a common cause of dysentery in Southeast Asia. Antimicrobials are thought to be beneficial for treatment; however, antimicrobial resistance in
Shigella
spp. is becoming widespread. We aimed to assess the frequency and mechanisms associated with decreased susceptibility to azithromycin in Southeast Asian
Shigella
isolates and use these data to assess appropriate susceptibility breakpoints.
Shigella
isolates recovered in Vietnam and Laos were screened for susceptibility to azithromycin (15 μg) by disc diffusion and MIC. Phenotypic resistance was confirmed by PCR amplification of macrolide resistance loci. We compared the genetic relationships and plasmid contents of azithromycin-resistant
Shigella sonnei
isolates using whole-genome sequences. From 475 available
Shigella
spp. isolated in Vietnam and Laos between 1994 and 2012, 6/181
S. flexneri
isolates (3.3%, MIC ≥ 16 g/liter) and 16/294
S. sonnei
isolates (5.4%, MIC ≥ 32 g/liter) were phenotypically resistant to azithromycin. PCR amplification confirmed a resistance mechanism in 22/475 (4.6%) isolates (
mphA
in 19 isolates and
ermB
in 3 isolates). The susceptibility data demonstrated the acceptability of the
S. flexneri
(MIC ≥ 16 g/liter, zone diameter ≤ 15 mm) and
S. sonnei
(MIC ≥ 32 g/liter, zone diameter ≤ 11 mm) breakpoints with a <3% discrepancy. Phylogenetic analysis demonstrated that decreased susceptibility has arisen sporadically in Vietnamese
S. sonnei
isolates on at least seven occasions between 2000 and 2009 but failed to become established. While the proposed susceptibility breakpoints may allow better recognition of resistant isolates, additional studies are required to assess the impact on the clinical outcome. The potential emergence of azithromycin resistance highlights the need for alternative options for management of
Shigella
infections in countries where
Shigella
is endemic.
In Vivo
Pharmacokinetics and Pharmacodynamics of APX001 against Candida spp. in a Neutropenic Disseminated Candidiasis Mouse Model
Authors: Zhao Miao , Lepak Alexander J. , VanScoy Brian , Bader Justin C. , Marchillo Karen , Vanhecker Jamie , Ambrose Paul G. , Andes David R.
Published: January 2018

APX001 is the prodrug of APX001A, which is a first-in-class small molecule with a unique mechanism of action that inhibits the fungal enzyme Gwt1 in the glycosylphosphatidylinositol (GPI) biosynthesis pathway. The goal of the present study was to determine which pharmacokinetic/pharmacodynamic (PK/PD) index and magnitude best correlated with efficacy in the murine disseminated candidiasis model for
Candida albicans
(
n
= 5),
C. glabrata
(
n
= 5), and
C. auris
(
n
= 4). MIC values ranged from 0.002 to 0.03 mg/liter for
C. albicans
, from 0.008 to 0.06 mg/liter for
C. glabrata
, and from 0.004 to 0.03 mg/liter for
C. auris
. Plasma APX001A pharmacokinetic measurements were performed in mice after oral administration of 4, 16, 64, and 256 mg/kg of body weight APX001. Single-dose pharmacokinetic studies exhibited maximum plasma concentration (
C
max
) values of 0.46 to 15.6 mg/liter, area under the concentration-time curve (AUC) from time zero to infinity (AUC
0–inf
) values of 0.87 to 70.0 mg · h/liter, and half-lives of 1.40 to 2.75 h. A neutropenic murine disseminated candidiasis model was utilized for all treatment studies, and drug dosing was by the oral route. Dose fractionation was performed against
C. albicans
K1, with total doses ranging from 4 to 1,024 mg/kg/day of APX001 fractionated into regimens of dosing every 3, 6, 8, and 12 h for a 24-h treatment duration. Nonlinear regression analysis was used to determine which PK/PD index best correlated with efficacy on the basis of the reduction in the number of CFU/kidney at 24 h. The 24-h free-drug AUC/MIC ratio (
f
AUC
0–24
/MIC) was the PK/PD index that best correlated with efficacy (coefficient of determination [
R
2
] = 0.88). Treatment studies with the remaining strains utilized regimens of 1 to 256 mg/kg of APX001 administered every 6 h for a 24-h duration with
C. albicans
and a 96-h study duration with
C. glabrata
and
C. auris
. The dose required to achieve 50% of the maximum effect (ED
50
) and stasis
f
AUC/MIC targets were as follows: for
C. albicans
, 3.67 ± 3.19 and 20.60 ± 6.50, respectively; for
C. glabrata
, 0.38 ± 0.21 and 1.31 ± 0.27, respectively; and for
C. auris
, 7.14 ± 4.54 and 14.67 ± 8.30, respectively. The present studies demonstrated
in vitro
and
in vivo
APX001A and APX001 potency, respectively, against
C. albicans
,
C. glabrata
, and
C. auris.
These results have potential relevance for clinical dose selection and evaluation of susceptibility breakpoints. The identification of a lower AUC/MIC ratio target for
C. glabrata
suggests that species-specific susceptibility breakpoints should be explored.
Bacterial Periplasmic Oxidoreductases Control the Activity of Oxidized Human Antimicrobial β-Defensin 1
Authors: Wendler J. , Ehmann D. , Courth L. , Schroeder B. O. , Malek N. P. , Wehkamp J.
Published: January 2018

The antimicrobial peptide human β-defensin 1 (hBD1) is continuously produced by epithelial cells in many tissues. Compared to other defensins, hBD1 has only minor antibiotic activity in its native state. After reduction of its disulfide bridges, however, it becomes a potent antimicrobial agent against bacteria, while the oxidized native form (hBD1ox) shows specific activity against Gram-negative bacteria. We show that the killing mechanism of hBD1ox depends on aerobic growth conditions and bacterial enzymes. We analyzed the different activities of hBD1 using mutants ofEscherichia colilacking one or more specific proteins of their outer membrane, cytosol, or redox systems. We discovered that DsbA and DsbB are essential for the antimicrobial activity of hBD1ox but not for that of reduced hBD1 (hBD1red). Furthermore, our results strongly suggest that hBD1ox uses outer membrane protein FepA to penetrate the bacterial periplasm space. In contrast, other bacterial proteins in the outer membrane and cytosol did not modify the antimicrobial activity. Using immunogold labeling, we identified the localization of hBD1ox in the periplasmic space and partly in the outer membrane ofE. coli. However, in resistant mutants lacking DsbA and DsbB, hBD1ox was detected mainly in the bacterial cytosol. In summary, we discovered that hBD1ox could use FepA to enter the periplasmic space, where its activity depends on presence of DsbA and DsbB. HBD1ox concentrates in the periplasm in Gram-negative bacteria, which finally leads to bleb formation and death of the bacteria. Thus, the bacterial redox system plays an essential role in mechanisms of resistance against host-derived peptides such as hBD1.
Diagnostic Testing for Zika Virus: a Postoutbreak Update
Authors: Theel Elitza S. , Hata D. Jane
Published: January 2018

Since the emergence and dissemination of Zika virus (ZIKV) in late 2015, our understanding of the biology, transmission, clinical disease, and potential sequelae associated with infection has markedly expanded. Over the past 2 years, the number of diagnostic assays for ZIKV has increased from none in 2015 to 5 serological assays and 14 molecular assays in 2017, all with emergency use authorization granted through the U.S. Food and Drug Administration. Here we provide an update on ZIKV, addressing what we have collectively learned since the outbreak began, including a summary of currently available diagnostic assays for this virus.
Porcine Epidemic Diarrhea Virus-Induced Epidermal Growth Factor Receptor Activation Impairs the Antiviral Activity of Type I Interferon
Authors: Yang Lijun , Xu Jiayu , Guo Longjun , Guo Taijie , Zhang Lu , Feng Li , Chen Hongyan , Wang Yue
Published: January 2018

Porcine epidemic diarrhea virus (PEDV) causes acute and devastating enteric disease in suckling piglets and results in huge economic losses in the pig industry worldwide. To establish productive infection, viruses must first circumvent the host innate immune response. In this study, we found that PEDV infection stimulated epidermal growth factor receptor (EGFR) activation, which has been linked to not only anticancer therapeutics, but also antiviral signaling. Therefore, we determined whether EGFR activation affected PEDV infection by using an activator or overexpression assay. The data showed that EGFR activation enhanced virus replication in both cases. We also found that specific inhibition of EGFR by either inhibitors or small interfering RNA (siRNA) led to a decrease in virus yields. Further analysis revealed that inhibition of EGFR produced augmentation of type I interferon genes. We next observed that the EGFR downstream cascade STAT3 was also activated upon PEDV infection. Similar to the case of EGFR, specific inhibition of STAT3 by either inhibitor or siRNA increased the antiviral activity of interferon and resulted in decreased PEDV RNA levels, and vice versa. The data on STAT3 depletion in combination with EGFR activation suggest that the attenuation of antiviral activity by EGFR activation requires activation of the STAT3 signaling pathway. Taken together, these data demonstrate that PEDV-induced EGFR activation serves as a negative regulator of the type I interferon response and provides a novel therapeutic target for virus infection.

IMPORTANCE
EGFR is a transmembrane tyrosine receptor that mediates various cellular events, as well as several types of human cancers. In this study, we investigated for the first time the role of EGFR in PEDV infection. We observed that PEDV infection induced EGFR activation. The role of EGFR activation is to impair the antiviral activity of type I interferon, which requires the involvement of the EGFR downstream signaling cascade STAT3. Our findings reveal a new mechanism evolved by PEDV to circumvent the host antiviral response, which might serve as a therapeutic target against virus infection.
Immunization of Pigs by DNA Prime and Recombinant Vaccinia Virus Boost To Identify and Rank African Swine Fever Virus Immunogenic and Protective Proteins
Authors: Jancovich James K. , Chapman Dave , Hansen Debra T. , Robida Mark D. , Loskutov Andrey , Craciunescu Felicia , Borovkov Alex , Kibler Karen , Goatley Lynnette , King Katherine , Netherton Christopher L. , Taylor Geraldine , Jacobs Bertram , Sykes Kathryn , Dixon Linda K.
Published: January 2018

African swine fever virus (ASFV) causes an acute hemorrhagic fever in domestic pigs, with high socioeconomic impact. No vaccine is available, limiting options for control. Although live attenuated ASFV can induce up to 100% protection against lethal challenge, little is known of the antigens which induce this protective response. To identify additional ASFV immunogenic and potentially protective antigens, we cloned 47 viral genes in individual plasmids for gene vaccination and in recombinant vaccinia viruses. These antigens were selected to include proteins with different functions and timing of expression. Pools of up to 22 antigens were delivered by DNA prime and recombinant vaccinia virus boost to groups of pigs. Responses of immune lymphocytes from pigs to individual recombinant proteins and to ASFV were measured by interferon gamma enzyme-linked immunosorbent spot (ELISpot) assays to identify a subset of the antigens that consistently induced the highest responses. All 47 antigens were then delivered to pigs by DNA prime and recombinant vaccinia virus boost, and pigs were challenged with a lethal dose of ASFV isolate Georgia 2007/1. Although pigs developed clinical and pathological signs consistent with acute ASFV, viral genome levels were significantly reduced in blood and several lymph tissues in those pigs immunized with vectors expressing ASFV antigens compared with the levels in control pigs.

IMPORTANCE
The lack of a vaccine limits the options to control African swine fever. Advances have been made in the development of genetically modified live attenuated ASFV that can induce protection against challenge. However, there may be safety issues relating to the use of these in the field. There is little information about ASFV antigens that can induce a protective immune response against challenge. We carried out a large screen of 30% of ASFV antigens by delivering individual genes in different pools to pigs by DNA immunization prime and recombinant vaccinia virus boost. The responses in immunized pigs to these individual antigens were compared to identify the most immunogenic. Lethal challenge of pigs immunized with a pool of antigens resulted in reduced levels of virus in blood and lymph tissues compared to those in pigs immunized with control vectors. Novel immunogenic ASFV proteins have been identified for further testing as vaccine candidates.
Combined treatment of primary vitreoretinal lymphomas significantly prolongs the time to first relapse
Authors: Klimova Aneta , Heissigerova Jarmila , Rihova Eva , Brichova Michaela , Pytlik Robert , Spicka Ivan , Mrazova Katerina , Karolova Jana , Svozilkova Petra
Published: January 2018

Background

Vitreoretinal lymphomas belong to the family of central nervous system (CNS) lymphomas. The optimal approach for the treatment of isolated primary vitreoretinal lymphoma is unclear because of the lack of large comparative clinical series. Combination of intravitreal and systemic chemotherapy is recommended in many reports. The aim of our retrospective study was to compare the survival rate and prognosis of patients with vitreoretinal lymphoma with and without CNS involvement.

Methods

Twenty patients with vitreoretinal lymphomas were observed between the years 2004and2016, 10 patients with primary vitreoretinal lymphoma and 10 with primary CNS lymphoma. To compare survival rates, we included 53 patients diagnosed with primary CNS lymphoma without vitreoretinal involvement between the years 2002and2011 from our haemato-oncology department.

Results

The 5-year survival rate was estimated 71% in patients with vitreoretinal lymphoma in our observation. Significantly longer 5-year overall survival (P˂0.01) was observed in patients with vitreoretinal lymphoma compared with patients with primary CNS lymphoma without vitreoretinal involvement. Progression-free survival was almost equal in both groups of patients with primary vitreoretinal lymphoma and primary CNS lymphoma (P=0.363). The relapse of lymphoma was frequent (50%–60%) with the median time to first relapse of 31 months. Combined treatment (local and systemic) in patients without CNS involvement significantly prolonged progression-free survival in our study (P˂0.05).

Conclusion

Combined treatment of primary vitreoretinal lymphoma significantly delays the relapse of lymphoma compared with local therapy alone. Intraocular involvement brings significant positive prognostic value when overall survival is compared.