bluuebunny/crossref_metadata_2025 huggingface dataset:
A general model of dielectric constant for porous materials
Authors: Liu Xing-Da , Hou Zhi-Ling , Zhang Bao-Xun , Zhan Ke-Tao , He Peng , Zhang Kai-Lun , Song Wei-Li
Published: March 2016

For eliminating the limits in the classical models, here we establish a general model for precisely predicting dielectric constant of porous materials. In this model, dielectric constant is independent on pore shapes when the pore size is far smaller than electromagnetic wavelengths; however, it depends on the porosities and correlation between the open pore direction and wave propagation direction. The structure factor β in the effective dielectric formula is 1 and 3 for through-hole and closed-pore materials, respectively. The experimental results are in good agreement with the model, suggesting a favorable tool for predicting dielectric properties of porous materials.
Quality characteristics of premium mutton nuggets enriched with almond-based functional components
Authors: Kumar R. R. , Sharma B. D. , Mendiratta S. K. , Malav O. P. , Talukder S. , Ahmad S. R.
Published: March 2016

Nuts, besides favourable fatty acid and nutrient profile, possess certain bioactive/functional compounds, which elicit several health benefits. Premium mutton nuggets with improved nutritional profile were developed by reducing the traditionally added animal fat in emulsion with the incorporation of almond paste. In order to substitute added fat by nut-based fat, standardised almond paste with 50% lipids in its proximate were explored at three levels (10%, 15% and 20%) to determine the optimum level of its incorporation. The extra lipid content of almond paste was adjusted by replacing lean on constant weight basis. The premium product was further analysed and compared with traditional product for detailed product profile, which included lipid profile, calorific value, dietary fibre, antioxidant activity and texture profile. Based on physico-chemical and sensory scores, the optimum level of incorporation for almond paste was adjudged as 15%. Developed premium mutton nuggets had significantly less (P < 0.05) cholesterol content, increased dietary fibre, enhanced antioxidant activity and acceptable texture profile. Thus, it was concluded that functional components of almond can be very well incorporated in the conventional process to develop a superior product.
Outcomes of the Australian Feral Camel Management Project and the future of feral camel management in Australia
Authors: Hart Quentin , Edwards Glenn
Published: March 2016

The Australian Feral Camel Management Project achieved its feral camel density targets at nominated environmental sites, with feral camel density being used as a de facto measure of feral camel impact. The project recognised that it was only the first step in a more concerted effort to bring feral camel impacts under control and therefore had a major focus on building capacity for future feral camel management. Although it had a management focus, the project provided a valuable opportunity to improve our knowledge of feral camel damage and management with an extensive monitoring and evaluation process. The final report of the project provides 24 recommendations that should be considered by all stakeholders in undertaking ongoing feral camel management.
Orange carotenoid protein burrows into the phycobilisome to provide photoprotection
Authors: Harris Dvir , Tal Ofir , Jallet Denis , Wilson Adjélé , Kirilovsky Diana , Adir Noam
Published: March 2016

Significance

Protection from overexcitation is one of the most important requirements of all photosynthetic organisms. Here we present a model based on coupled cross-linking/mass spectrometry and site-directed mutagenesis of the means by which the orange carotenoid protein (OCP) binds to the phycobilisome (PBS) antenna complex to avoid photodamage. The model shows that the protein must actively burrow into the complex, separating the PBS rings in the process. This penetration explains for the first time, to our knowledge, how the OCP carotenoid could approach the PBS chromophores at a distance that enables nonphotochemical quenching. However, the alteration in the core structure caused by OCP binding could also prevent energy transmission to the reaction centers.
Energy landscape in protein folding and unfolding
Authors: Mallamace Francesco , Corsaro Carmelo , Mallamace Domenico , Vasi Sebastiano , Vasi Cirino , Baglioni Piero , Buldyrev Sergey V. , Chen Sow-Hsin , Stanley H. Eugene
Published: March 2016

Significance

Protein folding represents an open question in science, and the free-energy landscape framework is one way to describe it. In particular, the role played by water in the processes is of special interest. To clarify these issues we study, during folding–unfolding, the temperature evolution of the magnetization for hydrophilic and hydrophobic groups of hydrated lysozyme using NMR spectroscopy. Our findings confirm the validity of the theoretical scenario of a process dominated by different energetic routes, also explaining the water role in the protein configuration stability. We also highlight that the protein native state limit is represented by the water singular temperature that characterizes its compressibility and expansivity and is the origin of the thermodynamical anomalies of its liquid state.
Human symbionts inject and neutralize antibacterial toxins to persist in the gut
Authors: Wexler Aaron G. , Bao Yiqiao , Whitney John C. , Bobay Louis-Marie , Xavier Joao B. , Schofield Whitman B. , Barry Natasha A. , Russell Alistair B. , Tran Bao Q. , Goo Young Ah , Goodlett David R. , Ochman Howard , Mougous Joseph D. , Goodman Andrew L.
Published: March 2016

Significance

The microbial community in the human gut represents one of the densest known ecosystems. Community composition has broad impacts on health, and metabolic competition and host selection have both been implicated in shaping these communities. Here, we report that contact-dependent bacterial antagonism also determines the ability of human gut symbionts to persist in the microbiome. Simplified microbiomes, assembled in gnotobiotic mice, reveal effector transmission rates exceeding 1 billion events per minute per gram of colonic contents. Together, these results suggest that human gut symbionts define their closest competitors not only metabolically but also spatially. Moreover, strains within a single species can encode diverse effectors that may provide new avenues for shaping the microbiome to improve human health.
Research funding and academic output: evidence from the Agricultural University of Athens
Authors: Drivas Kyriakos , Balafoutis Athanasios T. , Rozakis Stelios
Published: March 2016

This paper uses detailed data on funding information and research output from the Agricultural University of Athens to examine how each type of funding source is related to the quantity and quality of academic research output. Of special interest are private, Greek government and European Union sources of funding. We find that after controlling for unobserved heterogeneity from each research laboratory, all types of research funding are similarly related to both the count of publications and citations. Further, we find that research laboratories that have filed for at least one patent application produce more publications and citations to their work, indicating that laboratories that are close to industry are also engaged actively in research.
Renewing our faith in groups: a moral imperative for our community
Authors: Dunlap Peter T.
Published: March 2016

This paper is intended as a ‘practice’ in fostering the self-awareness of the Jungian community(ies) to stimulate what Andrew Samuels described as its ‘political energy’ – an energy that can be activated in intimate or larger group settings, which benefit from dynamic interactions and immediacy of affect. Such energy can also be generated remotely by appealing to the intellect and imagination. Here, I aim to activate political energy using what Joseph Henderson termed a ‘psychological attitude’ – that is, focusing on intervention and the potential for improvement. I invite us to consider what factors constrain and enable our political energy, with a view to understanding its nature more generally. This in turn will offer useful insights that we can integrate into our psychology.
A Peptidoglycan-Remodeling Enzyme Is Critical for Bacteroid Differentiation in Bradyrhizobium spp. During Legume Symbiosis
Authors: Gully Djamel , Gargani Daniel , Bonaldi Katia , Grangeteau Cédric , Chaintreuil Clémence , Fardoux Joël , Nguyen Phuong , Marchetti Roberta , Nouwen Nico , Molinaro Antonio , Mergaert Peter , Giraud Eric
Published: March 2016

In response to the presence of compatible rhizobium bacteria, legumes form symbiotic organs called nodules on their roots. These nodules house nitrogen-fixing bacteroids that are a differentiated form of the rhizobium bacteria. In some legumes, the bacteroid differentiation comprises a dramatic cell enlargement, polyploidization, and other morphological changes. Here, we demonstrate that a peptidoglycan-modifying enzyme in Bradyrhizobium strains, a DD-carboxypeptidase that contains a peptidoglycan-binding SPOR domain, is essential for normal bacteroid differentiation in Aeschynomene species. The corresponding mutants formed bacteroids that are malformed and hypertrophied. However, in soybean, a plant that does not induce morphological differentiation of its symbiont, the mutation does not affect the bacteroids. Remarkably, the mutation also leads to necrosis in a large fraction of the Aeschynomene nodules, indicating that a normally formed peptidoglycan layer is essential for avoiding the induction of plant immune responses by the invading bacteria. In addition to exopolysaccharides, capsular polysaccharides, and lipopolysaccharides, whose role during symbiosis is well defined, our work demonstrates an essential role in symbiosis for yet another rhizobial envelope component, the peptidoglycan layer.
Exploring Diversity and Origins of Streptomycin-Resistant Erwinia amylovora Isolates in New York Through CRISPR Spacer Arrays
Authors: Tancos K. A. , Cox K. D.
Published: March 2016

Streptomycin is the most effective and widely used chemical control in the eastern United States for blossom blight of apple caused by Erwinia amylovora; however, resistance to this antibiotic has been a concern in New York since 2002. From 2011 to 2014, statewide collections of E. amylovora were conducted resulting in the isolation of streptomycin-resistant (SmR) E. amylovora from several commercial orchards. Further genetic analysis of isolates was necessary to understand the origins and the diversity of these bacteria. Clustered regularly interspaced short palindromic repeat (CRISPR) spacer sequencing was employed to explore the diversity and possible origins of New York SmR E. amylovora isolates. The spacer array CR1, CR2, and CR3 regions of 27 SmR E. amylovora isolates and 76 streptomycin-sensitive (SmS) E. amylovora isolates were amplified and subsequently sequenced, revealing 19 distinct CRISPR spacer profiles for New York isolates. The majority of SmR E. amylovora isolates had the same CRISPR profile as SmR E. amylovora isolates discovered in 2002. This may infer that eradication efforts in 2002 failed and the bacterial populations continued to spread throughout the state. Several CRISPR profiles for SmR E. amylovora were identical to SmS E. amylovora collected from the same orchards, leading to the hypothesis that resistance may be developing within New York. Profiles not unique to New York were identical to many isolates from the Midwestern, eastern, and western United States, implying that streptomycin resistance may be due to the introduction of SmR E. amylovora from other regions of the United States. The increased understanding as to how SmR E. amylovora isolates are introduced, evolve, or have become established afforded by CRISPR profiling has been useful for disease management and restricting the movement of streptomycin resistance in New York.
Rootstock Effects on Almond Leaf Scorch Disease Incidence and Severity
Authors: Krugner R. , Ledbetter C. A.
Published: March 2016

A 5-year field study was conducted to evaluate effects of duration and exclusion of Xylella fastidiosa infections on young almond tree performance and their links to tree vigor. ‘Nemaguard,’ ‘Okinawa,’ ‘Nonpareil,’ and Y119 were used as rootstocks for almond scion ‘Sonora.’ Among X. fastidiosa-infected trees, there was significant etiological heterogeneity with i) absence of leaf scorching symptoms in the presence of reduced growth, ii) presence of leaf scorching symptoms in the absence of reduced growth, and iii) severe leaf scorching and reduced growth. Trunk cross sectional areas of X. fastidiosa-infected trees grafted on ‘Nemaguard’ and ‘Nonpareil’ rootstocks were significantly smaller than noninfected trees, whereas trunk size of trees grafted on ‘Okinawa’ and Y119 was not affected by infection status. Severity of leaf scorching symptoms was highest on trees grafted on ‘Nonpareil’ rootstock, intermediate on ‘Okinawa’ and Y119, and lowest on ‘Nemaguard.’ X. fastidiosa infections and seasonal leaf scorching symptoms persisted on most inoculated trees throughout the study, except on trees grafted on ‘Nemaguard’ that manifested complete leaf scorching symptom remission and apparent elimination of the pathogen after the second year. Results indicate that depending on rootstock type X. fastidiosa can affect trunk size in a relatively short period and/or persist for years as trees grow.
What is the evidence for Sjögren's syndrome being triggered by viral infection? Subplot: infections that cause clinical features of Sjögren's syndrome
Authors: Nakamura Hideki , Kawakami Atsushi
Published: March 2016

Purpose of review

To clarify the involvement of viral infections in the pathogenesis of Sjögren's syndrome and to discuss whether viruses can be a trigger for the development of Sjögren's syndrome.

Recent findings

Although some viruses are candidate triggers of Sjögren's syndrome, we focus on human T lymphotropic virus type I (HTLV-I). Clinicoepidemiological studies show a relationship between HTLV-I and Sjögren's syndrome with a low frequency of salivary gland damage in magnetic resonance imaging, autoantibody production and ectopic germinal center in HTLV-I-associated myelopathy (HAM) patients with Sjögren's syndrome. Our recent study showed that HTLV-I has the potential to infect salivary gland epithelial cells (SGECs). After a coculture of HCT-5 (an HTLV-I-infected T-cell line derived from the cerebrospinal fluid) of an HAM patient and SGECs, we observed time-dependent increases in the levels of soluble intracellular adhesion molecule1, interferon gamma-induced protein 10 kDa and regulated on activation, normal T-cell expressed and secreted. In addition, SGECs themselves express these molecules along with the expression of HTLV-I proteins.

HTLV-I is involved in the pathogenesis of HTLV-I-seropositive patients with Sjögren's syndrome. By infecting CD4+ T cells in vivo, HTLV-I induces specific clinicopathological conditions. In addition, HTLV-I-infected SGECs have the potential to augment the expression of molecules involved in cell adhesion, inflammation and migration.
How Long Does (S)He Have? Retrospective Analysis of Outcomes After Palliative Extubation in Elderly, Chronically Critically Ill Patients
Authors: Pan Cynthia X. , Platis Dimitris , Maw Min Min , Morris Jane , Pollack Simcha , Kawai Fernando
Published: March 2016

Objective:

For chronically critically ill elderly patients on mechanical ventilation, prognosis for significant recovery may be minimal. These individuals, or their surrogates, may decide for “palliative extubation.” A common prognostic question arises: “How long does she/he have?” This study describes demographics, mortality, time to death, and factors associated with death after palliative extubation.

Design, Setting, and Patients:

Retrospective 3-year study in community hospital with ethnically diverse elderly population. Chronically critically ill patients followed from palliative extubation to death or survival to discharge.

Measures:

Mortality/survival following palliative extubation, time to death or discharge, factors associated with death.

Results:

Hundred and forty-eight subjects underwent palliative extubation. Mean age: 78 years, 60% female, ethnically diverse with 46% white, and 54% others. Top diagnostic categories: sepsis (47%) and respiratory failure (22%). After extubation, 114 patients (77%) died in hospital and 34 (23%) were discharged. Of those who died, median time to death 8.9 hours (range, 4 min to 7 d). Mortality proportion was 56% at 24 hours and increased with time. Factors associated with early death: Systolic blood pressure less than 90 (p = 0.002) and Charlson Comorbidity Index that is above 6 or 0 (p = 0.002).

Conclusions:

Palliative extubation at end of life was an option selected by an ethnically diverse elderly population. Approximately three-fourths of subjects died in hospital, and one-fourth was discharged alive. Over 50% who died did so within 24 hours, making this useful information for counseling and anticipatory planning. Subjects with systolic blood pressure less than 90 and Charlson Comorbidity Index that is very low or very high had higher mortality.
Myoepithelioma-like Tumor of the Vulvar Region Presenting as a Nonmyxoid Spindle-Cell Neoplasm: A Potential Histologic Mimicker of Solitary Fibrous Tumor
Authors: Kaku Yo , Goto Keisuke , Kabashima Kenji
Published: March 2016

A new entity termed “myoepithelioma-like tumor of the vulvar region (MELTVR)” has been proposed as a rare mesenchymal neoplasm of the vulvar area. Histologically, MELTVRs are usually similar to soft tissue myoepitheliomas; however, they have a characteristic immunoprofile, including positivity for estrogen receptor and negativity for S100 protein, and loss of SMARCB1 expression. In this first known case report of MELTVR, the authors present a case of MELTVR that was histologically categorized in a nonmyxoid spindle-cell tumor group and resembled solitary fibrous tumor rather than soft tissue myoepithelioma.
Polarized Microscopy in Lesions With Altered Dermal Collagen
Authors: Elbendary Amira , Valdebran Manuel , Parikh Kruti , Elston Dirk M.
Published: March 2016

Alterations in dermal collagen are noted in dermatofibroma, dermatofibrosarcoma protuberans, morphea, lichen sclerosus et atrophicus, hypertrophic scars, and keloids. The authors sought to determine whether variations in birefringence of collagen by polarized microscopy could be of help in diagnosing such conditions. Representative hematoxylin and eosin sections of 400 cases, including dermatofibroma, dermatofibrosarcoma protuberans, hypertrophic scars, keloid, morphea, and lichen sclerosus, were examined under polarized microscopy. Distinct patterns of birefringence of collagen for each disease were noted under polarized microscopy. This study highlights the use of polarized microscopy as adjunctive tool in differentiating different diseases with collagen alteration.
Reproducibility of Anaerobic and Pain Thresholds in Male Patients With Intermittent Claudication
Authors: da Rocha Chehuen Marcel , Cucato Gabriel Grizzo , Saes Glauco Fernandes , Costa Luiz Augusto Riani , Leicht Anthony Scott , Ritti-Dias Raphael Mendes , Wolosker Nelson , de Moraes Forjaz Cláudia Lúcia
Published: March 2016

PURPOSE:

Maximal and submaximal parameters assessed during treadmill tests are used to prescribe exercise training and assess exercise-induced adaptations in patients with intermittent claudication (IC). Although reproducibility of maximal parameters is well documented, the reproducibility of submaximal is not clear. The aim of this study was to identify the reproducibility (reliability and agreement) of heart rate (HR) and oxygen uptake (

JOURNAL/jcprh/04.03/01273116-201609000-00007/7FSM1/v/2023-09-11T074103Z/r/image-gif

o
2) measured at the anaerobic (AT) and the pain (PT) thresholds assessed during a maximal test in patients with IC.

METHODS:

Twenty male patients with IC underwent 2 cardiopulmonary treadmill tests to maximal pain. The HR and

JOURNAL/jcprh/04.03/01273116-201609000-00007/7FSM1/v/2023-09-11T074103Z/r/image-gif

o
2 at the AT and PT were identified, and differences between repeat tests were compared. Reliability was determined by intraclass coefficient correlation (ICC). Agreement was assessed by coefficient of variation (CV), standard error of measurement (SEM), smallest detectable difference (SDD), and limits of agreement (LOA).

RESULTS:

The

JOURNAL/jcprh/04.03/01273116-201609000-00007/7FSM1/v/2023-09-11T074103Z/r/image-gif

o
2 at AT and PT exhibited moderate reliability and moderate/good agreement (ICC = 0.73 and 0.70; CV = 9.6% and 11.1%, respectively). The HR at the AT and PT exhibited high reliability and good agreement (ICC = 0.87 and 0.92; SEM = 3.9 and 3.2 bpm; SDD = 10.8 and 8.8 bpm, respectively). The LOA for

JOURNAL/jcprh/04.03/01273116-201609000-00007/7FSM1/v/2023-09-11T074103Z/r/image-gif

o
2 at AT and PT were ≤20% and for HR ≤11 bpm.

CONCLUSIONS:

The

JOURNAL/jcprh/04.03/01273116-201609000-00007/7FSM1/v/2023-09-11T074103Z/r/image-gif

o
2 and HR measured at the AT and PT were moderately to highly reproducible in male patients with IC. The HR and

JOURNAL/jcprh/04.03/01273116-201609000-00007/7FSM1/v/2023-09-11T074103Z/r/image-gif

o
2 at AT and PT may be used to establish training intensity and evaluate training effectiveness for these patients in clinical practice and research.
Depression in patients with chronic pain attending a specialised pain treatment centre: prevalence and impact on health care costs
Authors: Rayner Lauren , Hotopf Matthew , Petkova Hristina , Matcham Faith , Simpson Anna , McCracken Lance M.
Published: March 2016

This cross-sectional study aimed to determine the prevalence and impact of depression on health care costs in patients with complex chronic pain. The sample included 1204 patients attending a tertiary pain management service for people with chronic disabling pain, unresponsive to medical treatment. As part of routine care, patients completed a web-based questionnaire assessing mental and physical health, functioning, and service use in the preceding 3 months. Depression was assessed using the 9-item Patient Health Questionnaire. Self-report health care utilisation was measured across 4 domains: general practitioner contacts, contacts with secondary/tertiary care doctors, accident and emergency department visits, and days hospitalised. The participation rate was 89%. Seven hundred and thirty-two patients (60.8%; 95% CI 58.0-63.6) met criteria for probable depression, and 407 (33.8%) met the threshold for severe depression. Patients with depression were more likely to be unable to work because of ill health and reported greater work absence, greater pain-related interference with functioning, lower pain acceptance, and more generalised pain. Mean total health care costs per 3-month period were £731 (95% CI £646-£817) for patients with depression, compared with £448 (95% CI £366-£530) for patients without depression. A positive association between severe depression and total health care costs persisted after controlling for key demographic, functional, and clinical covariates using multiple linear regression models. These findings reveal the extent, severity, and impact of depression in patients with chronic pain and make evident a need for action. Effective treatment of depression may improve patient health and functioning and reduce the burden of chronic pain on health care services.
Comparison of Intraoperative Indicators and Postoperative Efficacy in Treatment of Benign Ovarian Tumor: Laparoscopy Versus Open Surgery
Authors: Liang Feng , Xu Xia , Liang Bing
Published: March 2016

This study aimed to compare intraoperative indicators and postoperative efficacy between laparoscopy and open surgery managing benign ovarian tumors. A total of 180 patients with benign ovarian tumor were enrolled; 105 underwent laparoscopy (LA group) and 75 underwent open surgery (OS group). Postoperative parameters were recorded. Preoperative and postoperative serum follicle-stimulating hormone, luteinizing hormone, and estradiol (E2) levels were determined using a BHP9507 chemiluminescence analyzer. The preoperative and postoperative serum C-reactive protein (CRP) level was examined using a QuikRead go CRP analyzer. Serum white blood cell and neutrophil (Ne) percentage were determined using an XT-2000i hematology analyzer. Compared with the OS group, intraoperative blood loss was less and the postoperative anal exhaust time, active time spent out of bed, length of hospitalization, time of indwelling catheter, and time of body temperature returning to normal were shorter in the LA group (all P < 0.001); the number of cases of intraoperative and postoperative complications and analgesia was less in the LA group (all P < 0.05). Six months after operation, serum follicle-stimulating hormone, luteinizing hormone, and E2 levels in the LA group were higher than those in the OS group (all P < 0.05). On day 1 and day 3 after operation, serum white blood cell and CRP levels and Ne percentage in the LA group were lower than those in the OS group (all P < 0.05). Laparoscopy is efficient and safe for managing benign ovarian tumors with comparable results to open surgery, and it is able to alleviate postoperative inflammation and minimize damage to the ovaries.
Antiretroviral Therapy Adherence Enhancing Interventions for Adolescents and Young Adults 13–24 Years of Age: A Review of the Evidence Base
Authors: Shaw Sarah , Amico K. Rivet
Published: March 2016

Introduction:

Youth living with HIV are highly under-represented in the evidence base for adherence interventions, despite their diverse and unique needs and barriers.

Objective:

This systematic review aimed to identify antiretroviral therapy (ART) adherence interventions specifically targeting adolescents and young adults (defined as ages 13–24) with the goal of characterizing the evidence base.

Methods:

Articles were identified using the PubMed database and cover work published through September 14, 2015. Inclusion criteria: (1) average age 13 to 24, (2) HIV positive, (3) on or beginning ART, (4) intervention targeted ART adherence in full or in part, (5) reported adherence, viral load, and/or CD4 count outcomes. Strength of evidence was defined as level 1 [randomized controlled trial (RCT) with significance testing on outcomes], 2 (within group studies with statistical testing on outcomes), 3 (RCTs with descriptive results), or 4 (within group studies with descriptive results).

Results:

Of 151 articles, 10 met inclusion criteria. Published between 2003 and 2014, these studies evaluated diverse intervention approaches. Most were conducted in the US and were small pilots that have yet to be replicated despite promising results. Only 3 studies met criteria for highest level strength of evidence; 2 supported a phone-based counseling approach with adherence monitors and 1 for weekly individual and family counseling.

Conclusions:

Despite nearly 20 years passing since the wide-scale availability of ART, and clear recognition that adolescents and youth adults fair worse on the cascade of HIV care, the evidence base remains sparse and underdeveloped. Promising approaches need replication and more rigorous studies are desperately needed.
Safety of Gadobutrol
Authors: Endrikat Jan , Vogtlaender Kai , Dohanish Susan , Balzer Thomas , Breuer Josy
Published: March 2016

Objective

The aim of this study was to provide a systematic safety analysis of gadobutrol after more than 29 million applications in clinical routine.

Materials and Methods

Forty-two clinical development phase II to IV studies on gadobutrol or comparator and the postmarketing safety surveillance database for gadobutrol (1998–2015) were analyzed. Adverse events (AEs) and drug-related AEs were evaluated in the clinical development database and spontaneous adverse drug reactions (ADRs) in the postmarketing database. Subgroup analyses were run on patients with special medical history and on patients of different age groups.

Results

In the clinical development studies, 6809 and 2184 patients received gadobutrol or comparators, respectively. The incidence of drug-related AEs was 3.5% for both groups. With the exception of nausea (0.7% related cases in both groups), all other drug-related AEs were 0.3% or less in both groups. Hypersensitivity reactions were sporadic (<0.1%). Patients with history of allergies to contrast agents experienced slightly more drug-related AEs. No differences were seen between age groups.

The overall reporting rate of ADRs from postmarketing surveillance was 0.05%. The most frequent ADRs were anaphylactoid/hypersensitivity reactions, nausea, vomiting, and dyspnea.

For 3 single-agent reports of nephrogenic systemic fibrosis, using a conservative approach, association with gadobutrol could not be excluded.

Conclusions

Gadobutrol is well tolerated and has a favorable safety profile for patients of all age groups.
A model for competition for ribosomes in the cell
Authors: Raveh Alon , Margaliot Michael , Sontag Eduardo D. , Tuller Tamir
Published: March 2016

A single mammalian cell includes an order of 10
4
–10
5
mRNA molecules and as many as 10
5
–10
6
ribosomes. Large-scale simultaneous mRNA translation induces correlations between the mRNA molecules, as they all compete for the finite pool of available ribosomes. This has important implications for the cell's functioning and evolution. Developing a better understanding of the intricate correlations between these simultaneous processes, rather than focusing on the translation of a single isolated transcript, should help in gaining a better understanding of mRNA translation regulation and the way elongation rates affect organismal fitness. A model of simultaneous translation is specifically important when dealing with highly expressed genes, as these consume more resources. In addition, such a model can lead to more accurate predictions that are needed in the interconnection of translational modules in synthetic biology. We develop and analyse a general dynamical model for large-scale simultaneous mRNA translation and competition for ribosomes. This is based on combining several ribosome flow models (RFMs) interconnected via a pool of free ribosomes. We use this model to explore the interactions between the various mRNA molecules and ribosomes at steady state. We show that the compound system always converges to a steady state and that it always entrains or phase locks to periodically time-varying transition rates in any of the mRNA molecules. We then study the effect of changing the transition rates in one mRNA molecule on the steady-state translation rates of the other mRNAs that results from the competition for ribosomes. We show that increasing any of the codon translation rates in a specific mRNA molecule yields a local effect, an increase in the translation rate of this mRNA, and also a global effect, the translation rates in the other mRNA molecules all increase or all decrease. These results suggest that the effect of codon decoding rates of endogenous and heterologous mRNAs on protein production is more complicated than previously thought. In addition, we show that increasing the length of an mRNA molecule decreases the production rate of all the mRNAs.
Andrewes's christmas fairy tale: atypical thinking about cancer aetiology in 1935
Authors: Sankaran Neeraja , van Helvoort Ton
Published: March 2016

This paper uses a short ‘Christmas fairy-story for oncologists’ sent by Christopher Andrewes with a 1935 letter to Peyton Rous as the centrepiece of a reflection on the state of knowledge and speculation about the viral aetiology of cancer in the 1930s. Although explicitly not intended for public circulation at the time, the fairy-story merits publication for its significance in the history of ideas about viruses, which are taken for granted today. Andrewes and Rous were prominent members of the international medical research community and yet faced strong resistance to their theory that
viruses
could cause such tumours as chicken sarcomas and rabbit papillomas. By looking at exchanges between these men among themselves and other proponents of their theories and with their oncologist detractors, we highlight an episode in the behind-the-scenes workings of medical science and show how informal correspondence helped keep alive a vital but then heterodox idea about the role of viruses in causing cancer.
Older fathers’ children have lower evolutionary fitness across four centuries and in four populations
Authors: Arslan Ruben C. , Willführ Kai P. , Frans Emma , Verweij Karin J. H. , Myrskylä Mikko , Voland Eckart , Almqvist Catarina , Zietsch Brendan P. , Penke Lars
Published: March 2016

Higher paternal age at offspring conception increasesde novogenetic mutations (Kong et al., 2012). Based on evolutionary genetic theory we predicted that the offspring of older fathers would be less likely to survive and reproduce, i.e. have lower fitness. In a sibling control study, we find clear support for negative paternal age effects on offspring survival, mating and reproductive success across four large populations with an aggregate N > 1.3 million in main analyses. Compared to a sibling born when the father was 10 years younger, individuals had 4-13% fewer surviving children in the four populations. Three populations were pre-industrial (1670-1850) Western populations and showed a pattern of paternal age effects across the offspring’s lifespan. In 20th-century Sweden, we found no negative paternal age effects on child survival or marriage odds. Effects survived tests for competing explanations, including maternal age and parental loss. To the extent that we succeeded in isolating a mutation-driven effect of paternal age, our results can be understood to show thatde novomutations reduce offspring fitness across populations and time. We can use this understanding to predict the effect of increasingly delayed reproduction on offspring genetic load, mortality and fertility.
2C-Cas9: a versatile tool for clonal analysis of gene function
Authors: Di Donato Vincenzo , De Santis Flavia , Auer Thomas O. , Testa Noé , Sánchez-Iranzo Héctor , Mercader Nadia , Concordet Jean-Paul , Del Bene Filippo
Published: March 2016

CRISPR/Cas9-mediated targeted mutagenesis allows efficient generation of loss-of-function alleles in zebrafish. To date, this technology has been primarily used to generate genetic knockout animals. Nevertheless, the study of the function of certain loci might require tight spatiotemporal control of gene inactivation. Here, we show that tissue-specific gene disruption can be achieved by driving Cas9 expression with the Gal4/UAS system. Furthermore, by combining the Gal4/UAS and Cre/loxP systems, we establish a versatile tool to genetically label mutant cell clones, enabling their phenotypic analysis. Our technique has the potential to be applied to diverse model organisms, enabling tissue-specific loss-of-function and phenotypic characterization of live and fixed tissues.
Comprehensive benchmarking reveals H2BK20 acetylation as a distinctive signature of cell-state-specific enhancers and promoters
Authors: Kumar Vibhor , Rayan Nirmala Arul , Muratani Masafumi , Lim Stefan , Elanggovan Bavani , Xin Lixia , Lu Tess , Makhija Harshyaa , Poschmann Jeremie , Lufkin Thomas , Ng Huck Hui , Prabhakar Shyam
Published: March 2016

Although over 35 different histone acetylation marks have been described, the overwhelming majority of regulatory genomics studies focus exclusively on H3K27ac and H3K9ac. In order to identify novel epigenomic traits of regulatory elements, we constructed a benchmark set of validated enhancers by performing 140 enhancer assays in human T cells. We tested 40 chromatin signatures on this unbiased enhancer set and identified H2BK20ac, a little-studied histone modification, as the most predictive mark of active enhancers. Notably, we detected a novel class of functionally distinct enhancers enriched in H2BK20ac but lacking H3K27ac, which was present in all examined cell lines and also in embryonic forebrain tissue. H2BK20ac was also unique in highlighting cell-type-specific promoters. In contrast, other acetylation marks were present in all active promoters, regardless of cell-type specificity. In stimulated microglial cells, H2BK20ac was more correlated with cell-state-specific expression changes than H3K27ac, with TGF-beta signaling decoupling the two acetylation marks at a subset of regulatory elements. In summary, our study reveals a previously unknown connection between histone acetylation and cell-type-specific gene regulation and indicates that H2BK20ac profiling can be used to uncover new dimensions of gene regulation.
Risk management and firm value: recent theory and evidence
Authors: Krause Timothy A , Tse Yiuman
Published: March 2016

Purpose

– This paper aims to provide an update to the risk management literature, as it compiles a survey of 65 recent theoretical and empirical studies on the topic.

Design/methodology/approach

– This is a survey paper that summarizes recent theoretical and empirical research regarding the relationship between risk management and firm value.

Findings

– Recent empirical evidence provides support for theoretical propositions in the literature that risk management increases firm value and returns, while reducing return and cash flow volatility. The results are largely consistent with early findings, and there have been significant empirical advances that address concerns regarding the endogeneity of risk management practices relative to corporate financial decisions. The literature has become broader and deeper, as there are now studies with larger sample sizes across more industries and geographic areas.

Practical implications

– Firms that use sound risk management practices obtain higher valuations, achieve better financial performance and experience diminished costs of financial distress. Recent research has emerged regarding enterprise risk management and its potential for value creation and risk reduction.

Originality/value

– The paper provides a new compilation and synthesis of recent theoretical and empirical research in risk management that addresses many of the limitations of prior research.
Management of surgical instruments with radio frequency identification tags
Authors: Kusuda Kaori , Yamashita Kazuhiko , Ohnishi Akiko , Tanaka Kiyohito , Komino Masaru , Honda Hiroshi , Tanaka Shinichi , Okubo Takashi , Tripette Julien , Ohta Yuji
Published: March 2016

Purpose

– To prevent malpractices, medical staff has adopted inventory time-outs and/or checklists. Accurate inventory and maintenance of surgical instruments decreases the risk of operating room miscounting and malfunction. In our previous study, an individual management of surgical instruments was accomplished using Radio Frequency Identification (RFID) tags. The purpose of this paper is to evaluate a new management method of RFID-tagged instruments.

Design/methodology/approach

– The management system of RFID-tagged surgical instruments was used for 27 months in clinical areas. In total, 13 study participants assembled surgical trays in the central sterile supply department.

Findings

– While using the management system, trays were assembled 94 times. During this period, no assembly errors occurred. An instrument malfunction had occurred after the 19th, 56th, and 73th uses, no malfunction caused by the RFID tags, and usage history had been recorded. Additionally, the time it took to assemble surgical trays was recorded, and the long-term usability of the management system was evaluated.

Originality/value

– The system could record the number of uses and the defective history of each surgical instrument. In addition, the history of the frequency of instruments being transferred from one tray to another was recorded. The results suggest that our system can be used to manage instruments safely. Additionally, the management system was acquired of the learning effect and the usability on daily maintenance. This finding suggests that the management system examined here ensures surgical instrument and tray assembly quality.
Combined quality function deployment and logical framework analysis to improve quality of emergency care in Malta
Authors: Buttigieg Sandra Catherine , Dey Prasanta Kumar , Cassar Mary Rose
Published: March 2016

Purpose

– The purpose of this paper is to develop an integrated patient-focused analytical framework to improve quality of care in accident and emergency (A
&
E) unit of a Maltese hospital.

Design/methodology/approach

– The study adopts a case study approach. First, a thorough literature review has been undertaken to study the various methods of healthcare quality management. Second, a healthcare quality management framework is developed using combined quality function deployment (QFD) and logical framework approach (LFA). Third, the proposed framework is applied to a Maltese hospital to demonstrate its effectiveness. The proposed framework has six steps, commencing with identifying patients’ requirements and concluding with implementing improvement projects. All the steps have been undertaken with the involvement of the concerned stakeholders in the A
&
E unit of the hospital.

Findings

– The major and related problems being faced by the hospital under study were overcrowding at A
&
E and shortage of beds, respectively. The combined framework ensures better A
&
E services and patient flow. QFD identifies and analyses the issues and challenges of A
&
E and LFA helps develop project plans for healthcare quality improvement. The important outcomes of implementing the proposed quality improvement programme are fewer hospital admissions, faster patient flow, expert triage and shorter waiting times at the A
&
E unit. Increased emergency consultant cover and faster first significant medical encounter were required to start addressing the problems effectively. Overall, the combined QFD and LFA method is effective to address quality of care in A
&
E unit.

Practical/implications

– The proposed framework can be easily integrated within any healthcare unit, as well as within entire healthcare systems, due to its flexible and user-friendly approach. It could be part of Six Sigma and other quality initiatives.

Originality/value

– Although QFD has been extensively deployed in healthcare setup to improve quality of care, very little has been researched on combining QFD and LFA in order to identify issues, prioritise them, derive improvement measures and implement improvement projects. Additionally, there is no research on QFD application in A
&
E. This paper bridges these gaps. Moreover, very little has been written on the Maltese health care system. Therefore, this study contributes demonstration of quality of emergency care in Malta.
Critical success factors for implementation process of design-build projects in Vietnam
Authors: Dang Chau Ngoc , Le-Hoai Long
Published: March 2016

Purpose

– Design-build (DB) has become widely prosperous in recent years. This new approach could be applicable to construction projects in either developed or developing countries. However, the implementation process of DB in Vietnam encounters difficulties due to the unfamiliarity and inexperience with the approach. This study aims to identify the correlation and causality between critical success factors (CSFs) and DB project performance measured by key performance indicators (KPIs).

Design/methodology/approach

– A questionnaire was used to collect the project data from public and private sector DB projects in Vietnam. The correlation between CSFs and KPIs was identified through correlation analysis. Then, the causality was explored through regression analysis.

Findings

– The results of correlation indicate that parties’ capabilities play an important role in determining the success or failure of DB projects. In addition, the results of causality highlight six CSFs which significantly affect DB project performance, including resolving conflicts quickly; effective overall managerial actions in planning, organizing, leading and controlling; project participants’ satisfaction with the financial return from the project; competent multidisciplinary project team; project team members’ good/active attitudes to the job; and adequate funding throughout the project. It was also shown that there is no significant difference about the project performance between public and private sector DB projects.

Practical implications

– Identifying the correlation and causality between CSFs and different aspects of DB project performance could help project participants to know the controllable CSFs on which they must focus more. Hence, they could manage these CSFs properly to increase the chance of meeting time, cost and quality objectives of DB projects in which they are involved and achieving the owners’ satisfaction.

Originality/value

– The findings of this study could provide project participants in Vietnam, as well as similar developing countries, with a better understanding of the impact of CSFs on different aspects of DB project performance. Hence, they could make effective CSFs-based improvements on their management-oriented approaches to enhance different aspects of DB project performance.
A numerical definition-based systematic design approach for coupling consumers
'
image perception with product form
Authors: Chen Hung-Yuan , Chang Yu-Ming , Chang Hua-Cheng
Published: March 2016

Purpose

– This paper aims to propose a numerical definition-based systematic design approach (NDSDA) to generate an explicit numerical definition of the product form profile and to establish the correlation between the product form features and the corresponding consumers’ image perceptions.

Design/methodology/approach

– To illustrate the feasibility of the proposed method, this study considers the design of a two-dimensional automobile profile for illustration purposes and commences by developing a detailed numerical definition of an automobile profile using Bézier curves. A series of automobile image evaluations are conducted to examine the relationship between the characteristics of an automobile profile and its associated consumer image perception. Finally, the evaluation results are analyzed statistically, and the statistical results are used to construct mathematical models formalizing the correlations between the automobile profile design variables and the consumers’ perceptions of the product image.

Findings

– The results of the evaluation trials are used to construct mathematical models capable of predicting the likely consumer response to any automobile profile designed in accordance with the numerical definition. Furthermore, the evaluation data enable the critical design variables and form features to be determined such that the efficacy of the design process in creating automobiles which better meet the consumers’ image aspirations can be improved.

Originality/value

– The major contribution of the NDSDA methodology presented in this study is the ability it gives to designers to specify the product form in a detailed yet highly efficient manner. Furthermore, the numerical definition of the product form not only provides a suitable basis for identifying the critical design variables and form features of the product but also provides an understanding of how these variables should be manipulated to obtain or reinforce the desired product image.