bluuebunny/crossref_metadata_2025 huggingface dataset:
BILATERAL COATS REACTION IN BANNAYAN–ZONANA SYNDROME: A SINGLE CASE REPORT
Authors: Klifto Meredith R. , Balaratnasingam Chandrakumar , Weissman Harold H. , Yannuzzi Lawrence A.
Published: May 2016

Purpose:

To report the clinical features of bilateral Coats reaction in a patient with Bannayan–Zonana syndrome.

Methods:

The clinical course and retinal manifestations of a 21-year-old patient with Bannayan–Zonana syndrome and bilateral Coats reaction were studied. Retinal manifestations were documented with clinical examination, ultrawide-field color imaging, and ultrawide-field fluorescein angiography.

Results:

Best-corrected visual acuities were 20/25 OD and 20/25 OS. Anterior segment examinations were normal bilaterally. The inferotemporal quadrant of the left retina demonstrated retinal telangiectasias, exudation, and a neurosensory retinal detachment extending to the mid-periphery. Fluorescein angiography demonstrated bilateral peripheral nonperfusion and vascular staining. An epiretinal membrane also involved the left macula.

Conclusion:

Bannayan–Zonana syndrome is an autosomal-dominant, hamartomatous disease characterized by a mutation spectrum that involves genes responsible for vascular development. Retinal vascular abnormalities and exudation can be a manifestation of this syndrome.
Abnormal Pupil Finding After an Orbital Floor Fracture in a Child
Authors: Feng Jing Jing , Della Rocca David A. , Kodsi Sylvia R.
Published: May 2016

Purpose:

Trauma to the pupillary fibers can occur during repair of orbital floor fracture resulting in a fixed and dilated pupil. The authors report, discuss, and propose an etiology of an abnormal pupil in a child with an orbital floor fracture before surgical repair.

Methods:

A case report is described.

Results:

Although the orbital fracture was repaired, anisocoria persisted 18 months after the initial trauma.

Conclusions:

Pupillary function must be assessed before surgical repair of an orbital floor fracture as damage of the pupillary fibers can occur secondary to the orbital floor fracture.
Efficacy of mirtazapine for the treatment of fibromyalgia without concomitant depression: a randomized, double-blind, placebo-controlled phase IIa study in Japan
Authors: Miki Kenji , Murakami Masato , Oka Hiroshi , Onozawa Kaname , Yoshida Sadahiro , Osada Kenichi
Published: May 2016

To evaluate the efficacy and safety of mirtazapine in Japanese patients with fibromyalgia (FM), a parallel-group, randomized, double-blind, placebo-controlled phase IIa study was conducted at 57 sites between November 2012 and February 2014. Patients aged 20 to 64 years who met the American College of Rheumatology 1990 diagnostic FM criteria and had stably high pain scores during a placebo run-in period were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to receive mirtazapine orally (15 mg/d for 1 week and then 30 mg/d) or matching placebo for 12 weeks. The primary endpoint was change in mean numerical rating scale (NRS) pain score from baseline to endpoint (week 12 or early discontinuation). Of the 430 patients randomized (n = 215 each group), 422 (n = 211 each group) were analyzed for the primary endpoint. At the study endpoint, mirtazapine caused a significantly greater reduction in the mean NRS pain score compared with placebo (difference, 0.44; 95% confidence interval, −0.72 to −0.17; P = 0.0018). The reduction by mirtazapine remained significantly greater compared with placebo from week 6 onward. More patients treated with mirtazapine had their NRS pain score reduced by ≥30% from baseline (45.5% vs 30.8%). Mirtazapine also improved pain-related quality of life assessed by the Japanese version of the Fibromyalgia Impact Questionnaire and the Short-Form 36 Questionnaire. Adverse events were more common with mirtazapine than placebo (68.8% vs 56.7%), including somnolence (32.1% vs 7.4%), weight gain (17.7% vs 0.9%), and increased appetite (11.6% vs 3.3%). In conclusion, mirtazapine was an effective and safe treatment for Japanese patients with FM.
Implant-Based Breast Reconstruction Using a Polyester Mesh (Surgimesh-PET): A Retrospective Single-Center Study
Authors: Baldelli Ilaria , Cardoni Gaia , Franchelli Simonetta , Fregatti Piero , Friedman Daniele , Pesce Marianna , Ponte Erica , Santori Gregorio , Santi Pierluigi
Published: May 2016

Background:

Although the introduction of acellular dermal matrices is considered one of the most important advancements in alloplastic breast reconstruction, costs and local policy limit their use in Italy. The purpose of this study was to assess short-term outcomes following Surgimesh-PET–based breast reconstruction.

Methods:

A single-center, retrospective, case-control study was performed from January 1, 2012, to December 31, 2013, by enrolling 206 breast reconstructions performed in 196 patients after oncologic (n = 200) or prophylactic (n = 6) mastectomy. Group A included 63 patients who underwent 70 immediate Surgimesh-PET–assisted breast reconstructions, and group B included 133 patients who underwent 136 standard breast reconstructions.

Results:

No significant differences between groups occurred for early postoperative complications (p = 0.610), major complications that required surgical revision (p = 0.887), volume (p = 0.498) or width of the prosthesis (p = 0.201), skin-sparing mastectomy (p = 0.315), or axillary surgery (p = 0.265). Multivariate logistic regression showed that prior radiotherapy was the only significant variable for early postoperative complications in both whole series (p = 0.011) and group B (p = 0.046), whereas body mass index greater than 25 was an independent predictor in group A (p = 0.041). Prior radiotherapy was the only variable that reached statistical significance in the multivariate model for major complications in the whole series (p = 0.005).

Conclusions:

Short-term outcomes of Surgimesh-PET–based alloplastic breast reconstruction are promising. Further studies are needed to evaluate the long-term results of this surgical approach.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Proteins as templates for complex synthetic metalloclusters: towards biologically programmed heterogeneous catalysis
Authors: Fehl Charlie , Davis Benjamin G.
Published: May 2016

Despite nature’s prevalent use of metals as prosthetics to adapt or enhance the behaviour of proteins, our ability to programme such architectural organization remains underdeveloped. Multi-metal clusters buried in proteins underpin the most remarkable chemical transformations in nature, but we are not yet in a position to fully mimic or exploit such systems. With the advent of copious, relevant structural information, judicious mechanistic studies and the use of accessible computational methods in protein design coupled with new synthetic methods for building biomacromolecules, we can envisage a ‘new dawn’ that will allow us to build de novo metalloenzymes that move beyond mono-metal centres. In particular, we highlight the need for systems that approach the multi-centred clusters that have evolved to couple electron shuttling with catalysis. Such hybrids may be viewed as exciting mid-points between homogeneous and heterogeneous catalysts which also exploit the primary benefits of biocatalysis.
Metabolic rate covaries with fitness and the pace of the life history in the field
Authors: Pettersen Amanda K. , White Craig R. , Marshall Dustin J.
Published: May 2016

Metabolic rate reflects the ‘pace of life’ in every organism. Metabolic rate is related to an organism's capacity for essential maintenance, growth and reproduction—all of which interact to affect fitness. Although thousands of measurements of metabolic rate have been made, the microevolutionary forces that shape metabolic rate remain poorly resolved. The relationship between metabolic rate and components of fitness are often inconsistent, possibly because these fitness components incompletely map to actual fitness and often negatively covary with each other. Here we measure metabolic rate across ontogeny and monitor its effects on actual fitness (lifetime reproductive output) for a marine bryozoan in the field. We also measure key components of fitness throughout the entire life history including growth rate, longevity and age at the onset of reproduction. We found that correlational selection favours individuals with higher metabolic rates in one stage and lower metabolic rates in the other—individuals with similar metabolic rates in each developmental stage displayed the lowest fitness. Furthermore, individuals with the lowest metabolic rates lived for longer and reproduced more, but they also grew more slowly and took longer to reproduce initially. That metabolic rate is related to the pace of the life history in nature has long been suggested by macroevolutionary patterns but this study reveals the microevolutionary processes that probably generated these patterns.
Social life and sanitary risks: evolutionary and current ecological conditions determine waste management in leaf-cutting ants
Authors: Farji-Brener Alejandro G. , Elizalde Luciana , Fernández-Marín Hermógenes , Amador-Vargas Sabrina
Published: May 2016

Adequate waste management is vital for the success of social life, because waste accumulation increases sanitary risks in dense societies. We explored why different leaf-cutting ants (LCA) species locate their waste in internal nest chambers or external piles, including ecological context and accounting for phylogenetic relations. We propose that waste location depends on whether the environmental conditions enhance or reduce the risk of infection. We obtained the geographical range, habitat and refuse location of LCA from published literature, and experimentally determined whether pathogens on ant waste survived to the high soil temperatures typical of xeric habitats. The habitat of the LCA determined waste location after phylogenetic correction: species with external waste piles mainly occur in xeric environments, whereas those with internal waste chambers mainly inhabit more humid habitats. The ancestral reconstruction suggests that dumping waste externally is less derived than digging waste nest chambers. Empirical results showed that high soil surface temperatures reduce pathogen prevalence from LCA waste. We proposed that LCA living in environments unfavourable for pathogens (i.e. xeric habitats) avoid digging costs by dumping the refuse above ground. Conversely, in environments suitable for pathogens, LCA species prevent the spread of diseases by storing waste underground, presumably, a behaviour that contributed to the colonization of humid habitats. These results highlight the adaptation of organisms to the hygienic challenges of social living, and illustrate how sanitary behaviours can result from a combination of evolutionary history and current environmental conditions.
A study of a real-time online monitoring system for the durability of concrete structures
Authors: Xiao Mingming , Zhang Shilong , Tang Yanbing , Lin Zhongmao , Chen Jiahong
Published: May 2016

Purpose

This study aims to explore the effect of corrosion monitoring technology for ensuring concrete structure safety.

Design/methodology/approach

A new monitoring system scheme with unattended operation to evaluate the durability of concrete structures is presented, which includes four components, namely, a multi-function embedded sensor, a microprocessor data collecting module, a system data analysis and storage module, and a remote server module.

Findings

The system carries out monitoring of chloride ion concentration and pH in concrete, corrosion current density and of the self-corrosion potential of the reinforcing steel bar.

Originality/value

This system provides real-time, online, lossless monitoring for concrete structures.
Cost of employee loyalty@Anand Finance
Authors: Chowdary Nagendra V. , Jayakumar Vandana , Muthukumar R.
Published: May 2016

Subject area

Organizational Behavior and Strategic Management.

Study level/applicability

MBA, Management/Executive development programs.

Case overview

This case study can be used effectively for understanding the nuances of employee loyalty, especially if there is a cost of employee loyalty. While Anand Finance is happy that its workforce has largely been loyal, the volatile, uncertain, complex and ambiguous times force it to chart new course of action. The newly appointed Business Head, Ashok Singh's challenges compound when he finds that there was not’t a single innovation or best practice adopted over the past three years. Given his mandate to make Anand Finance as the Walmart of financial services, can he aspire to rally the forces behind the new mission? This case study facilitates an interesting discussion on the significance of operational and strategic alignment at organizations in the backdrop of an interesting story of Anand Finance, one of the leading non-banking financial companies (NBFCs) in India. The non-alignment was noticed by Ashok Singh (Singh) who took over as the Business Head of Anand Finance. While the company boasted of long-standing employees, Singh was quick to notice that the company had been paying a cost for employee loyalty. What was the cost of employee loyalty? Singh could also sense that the company was in a state of active inertia. Expected to make Anand Finance Walmart for financial services by 2025, Singh had a big task at hand given the lack of strategic orientation of the employees. What would be the likely course of Singh's actions? As the case study deals with strategic dilemmas related to the organizational culture, it can be suitably used for organizational behavior and strategic management courses. This case study is meant highlight that even if an organization is operationally sound and successful, it cannot afford to be strategically disoriented, as its strengths may prove to be its weaknesses with changing business conditions.

Expected learning outcomes

At the end of this case discussion, the participants are expected to know the merits and demerits of employee loyalty and the implications of the same for organizational change; whether employees’ relatively longer stints at companies would contribute to active inertia (as defined by Donald N. Sull in Harvard Business Review article, “Why Good Companies Go Bad”); and the ways to align operational orientation with strategic mindset, especially in the case of employees who rose through the ranks and had been serving the company for relatively longer period.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.
The formation of new inter-firm relationships: a UK offshore wind sector analysis
Authors: Hennelly Patrick , Wong Chee Yew
Published: May 2016

Purpose

The focus of this paper is to understand the initial formation of inter-firm relationship with the ultimate aim to form a long-term relationship in offshore-wind sector. The research question is “How and why new inter-firm relationships are built in nascent industries with highly uncertain business environments?”

Design/methodology/approach

Longitudinal case studies of three pairs of new inter-firm relationships based on interviews and other archival data are analysed.

Findings

Not all new inter-firm relationships progressed to expansion stage, largely owing to incompatibility and uncertainty. In some cases incompatibility could be rectified by trust and sharing of information. High trust is required to move the relationship from awareness to exploration stage. Investment in R&D is required to move the relationship from exploration to expansion. Innovation complementarity is the key in OSW sector.

Practical implications

Provide insights into how new inter-firm relationships in OSW sector could fail or be built up. High trust at the beginning helps to lower risk and encourages further investment.

Originality/value

Inform inter-firm relationship theories under high market risk and political uncertainty, especially for OSW sector.
Characterization of metals in air and soil near a steel making plant in the North part of Italy
Authors: Rada Elena C. , Ragazzi Marco , Tubino Marco , Gambaro Andrea , Turetta Clara , Argiriadis Elena , Vecchiato Marco , Rossi Barbara , Tava Maurizio
Published: May 2016

Purpose

– The purpose of this paper is to define suitable tracers that are particularly significant in assessing the impact on the surrounding environment caused by a steel making plant.

Design/methodology/approach

– The authors focussed on the detection and quantification of inorganic pollutants such as heavy metals in the soil and in the air in the surrounding area of the steel making plant. The presented data, concerning a plant in the North part of Italy, come from an approach that took into account the advantages of different devices and sampling criteria: apart from conventional devices, two kinds of deposimeters have been used (for characterizing either total or wet/dry depositions). Their locations have been chosen taking into account the distance from the plant.

Findings

– The paper demonstrates that the presence of diffused emissions plays an important (negative) role still today; thus a modern plant should reduce this kind of emission in order to be accepted from the population living in the surroundings. In the analyzed case study, the benefits of adopting the best available technologies can be seen from the temporal variability of the incidence of the plant.

Originality/value

– The value of the paper is in the support that it can give to decision makers that must manage a steel making plant in an area.
Effect of irregularity and anisotropy on the dynamic response due to a shear load moving on an irregular orthotropic half-space under influence of gravity
Authors: Singh Abhishek K. , Lakshman Anirban , Chattopadhyay Amares
Published: May 2016

Purpose

– The response of moving load over a surface is a subject of investigation because of its possible applications in determining the strength of a structure. Recently, with the enlargement of high-speed train networks, concern has been expressed about the effects of moving loads on the track, embankment and nearby structures. Earth surface and artificial structure are not always regular in nature. Irregularities are also responsible for structural collapse of long bridge and highway of plateau area under the action of moving loads. The purpose of this paper is to investigate the influence of irregularity on dynamic response due to a moving shear load.

Design/methodology/approach

– At first the authors developed the mathematical model for the problem which is comprised of equation of motion together with boundary conditions. Perturbation technique has been used to derive the stresses produced in an irregular orthotropic half-space (which is influenced by gravity) due to a moving shear load. MATLAB and MATHEMATICA softwares have been employed for numerical computation as well as graphical illustration.

Findings

– In this paper the authors have discussed the stresses produced in an irregular gravitating orthotropic half-space due to a moving shear load. The expression for shear stress has been established in closed form. Substantial effects of depth, irregularity factor, maximum depth of irregularity and gravitational parameter on shear stress have been reported. These effects are also exhibited by means of graphical illustration and numerical computation for an orthotropic material T300/5208 graphite/epoxy which is broadly used in aircraft designing. Moreover, comparison made through meticulous examination for different types of irregularity, presence and absence of anisotropy and gravity are highlighted.

Practical implications

– A number of classical fatigue failures occur in aircraft structures. The moving load responsible for such fatigue failure may occur during manufacturing process, servicing, etc. Apart from these the aircraft structures may also experience load because of environmental damages (such as lightning strike, overheat) and mechanical damages (like impact damage, overload/bearing failure). Therefore the present study is likely to find application in the field of construction of highways, airport runways and earthquake engineering.

Originality/value

– To the best of the authors’ knowledge no problem related to moving load on irregular orthotropic half-space under influence of gravity has been attempted by any author till date. Furthermore comparative study for different types of irregularity, presence and absence of anisotropy and influence of gravity on the dynamic response of moving load are novel and major highlights of the present study.
Plum Island Coffee Roasters: a perfect blend of coffee, business and community
Authors: Foudray Gregory C.
Published: May 2016

Synopsis

The owner of an independent coffee shop is looking for methods to improve the sales performance of his business. He has strong customer sales and service skills but limited formal business education. He believes his sales are growing but seasonal volatility in sales is affecting his profitability. The manager of the coffee shop is a college student and is attempting to use methods from her business courses to analyze the impact of Facebook Advertising on the sales of the coffee shop. On a busy Friday in May, they are meeting to make key marketing decisions.

Research methodology

This case is a field researched case. The author had full access to the owner of the business, meeting with him frequently over a two-year period. The business owner has reviewed the case to verify its accuracy.

Relevant courses and levels

This case is intended for use in undergraduate business courses in the subject areas of Business, Marketing and Social/Digital Media Marketing.
Application of the Syllk model wiring an organisation for the capability of an online community of practice
Authors: Duffield Stephen Mark
Published: May 2016

Purpose

This paper aims to demonstrate how to apply the systemic lessons learned knowledge (Syllk) model to enable the organisation for the capability of an online community of practice (CoP).

Design/methodology/approach

The research method consisted of multiple spiral “action research” cycles (plan, action, observe and reflect) within a government organisation. The initial planning stage consisted of interviews followed by two focus groups to identify the facilitators and barriers that impact the initial design of the Syllk model within the organisation. Established knowledge management practices were aligned with each of the Syllk elements to address the identified barriers and facilitate learning as the action cycles progressed. Online CoP initiatives were implemented with two action research cycles completed. Actions were observed, monitored, evaluated and reflected on using an after action review process.

Findings

The results from this research shows how the capability of a CoP can be “wired” (distributed) across organisational systems, and how the Syllk model can be used to conceptually facilitate this. The research highlights the importance in understanding organisational knowledge facilitators and barriers and the associated practices to reflect and learn from past experiences.

Research limitations/implications

The paper demonstrates an application of the Syllk model, and that action research can benefit project and knowledge management researchers and practitioners.

Practical implications

This study contributes to practice by highlighting how to use the Syllk model to “wire” an organisation for some know-how capability.

Originality/value

This study applies a conceptual model enabling management to understand how organisational know-how is distributed (wired) across various systems of an organisation for an online CoP.
The role of knowledge sharing culture in business performance
Authors: Marouf Laila
Published: May 2016

Purpose

The aim of this study is to investigate the role of knowledge sharing (KS) culture in leveraging knowledge management (KM) strategy and human resource (HR) strategy to improve business performance (BP).

Design/methodology/approach

A structured questionnaire survey was distributed to 120 randomly selected companies in Kuwait. A total of 392 valid responses were collected and tested using a structural equation model. Statistical analysis was conducted using SPSS and LISREL software to verify the research hypotheses.

Findings

The results revealed the impact of the mediating variable KS culture on the enhancement of BP. Both KM strategy and HR strategy were observed to have a positive direct effect on KS culture.

Practical implications

The results indicate that top management should make efforts to cultivate a KS culture to achieve better BP and future success.

Originality/value

The primary research contribution is the conceptual model for the role of KS culture as a mediator between KM strategy, HR strategy and BP.
Incorporation of poison center services in a state‐wide overdose education and naloxone distribution program
Authors: Doyon Suzanne , Benton Carleigh , Anderson Bruce A. , Baier Michael , Haas Erin , Hadley Lisa , Maehr Jennifer , Rebbert‐Franklin Kathleen , Olsen Yngvild , Welsh Christopher
Published: May 2016

Background

To help curb the opioid overdose epidemic, many states are implementing overdose education and naloxone distribution (OEND) programs. Few evaluations of these programs exist. Maryland's OEND program incorporated the services of the poison center. It asked bystanders to call the poison center within 2 hours of administration of naloxone. Bystanders included law enforcement (LE).

Objective

Description of the initial experience with this unique OEND program component.

Methods

Retrospective case series of all cases of bystander‐administered naloxone reported to the Maryland Poison Center over 16 months. Cases were followed to final outcome, for example, hospital discharge or death. Indications for naloxone included suspected opioid exposure and unresponsiveness, respiratory depression, or cyanosis. Naloxone response was defined as person's ability to breathe, talk, or walk within minutes of administration.

Results

Seventy‐eight cases of bystander‐administered naloxone were reported. Positive response to naloxone was observed in 75.6% of overall cases. Response rates were 86.1% and 70.9% for suspected exposures to heroin and prescription opioids, respectively. Two individuals failed to respond to naloxone and died.

Discussion

Naloxone response rates were higher and admission to the intensive care unit rates were lower in heroin overdoses than prescription opioid overdoses.

Conclusions

This retrospective case series of 78 cases of bystander‐administered naloxone reports a 75.6% overall rate of reversal.

Scientific Significance

The findings of this study may be more generalizable. Incorporation of poison center services facilitated the capture of more timely data not usually available to OEND programs. (Am J Addict 2016;25:301–306)
Re‐irradiation using proton beam therapy combined with weekly intra‐arterial chemotherapy for recurrent oral cancer
Authors: Hayashi Yuichiro , Nakamura Tatsuya , Mitsudo Kenji , Kimura Kanako , Yamaguchi Hisashi , Ono Takashi , Azami Yusuke , Takayama Kanako , Hirose Katsumi , Yabuuchi Tomonori , Suzuki Motohisa , Hatayama Yoshiomi , Kikuchi Yasuhiro , Wada Hitoshi , Fuwa Nobukazu , Hareyama Masato , Tohnai Iwai
Published: May 2016

Aim

The purpose of this study was to clarify the efficacy and toxicities of re‐irradiation using proton beam therapy combined with weekly intra‐arterial chemotherapy for recurrent oral cancer.

Methods

Between October 2009 and July 2014, 34 patients who had recurrent oral cancer were treated by proton beam therapy combined with intra‐arterial infusion chemotherapy at the Southern Tohoku Proton Therapy Center, Japan.

Results

For all patients, the median follow‐up was 25 months (range, 3–77 months). After treatment, 22 patients (65%) achieved a complete response, and 12 patients (35%) achieved a partial response at the primary tumor site. One‐year and 2‐year overall survival (OS) rates were 62% and 42%, respectively. One‐year and 2‐year LC rates were 77% and 60%, respectively. No treatment‐related deaths were observed during the treatment and follow‐up periods.

Conclusion

Re‐irradiation using proton beam therapy combined with weekly intra‐arterial chemotherapy improved OS and local control rates compared with other treatment modalities and could become a new treatment modality for patients with recurrent oral cancer.
Randomised clinical trial: a phase 1, dose‐ranging study of the anti‐matrix metalloproteinase‐9 monoclonal antibody GS‐5745 versus placebo for ulcerative colitis
Authors: Sandborn W. J. , Bhandari B. R. , Fogel R. , Onken J. , Yen E. , Zhao X. , Jiang Z. , Ge D. , Xin Y. , Ye Z. , French D. , Silverman J. A. , Kanwar B. , Subramanian G. M. , McHutchison J. G. , Lee S. D. , Shackelton L. M. , Pai R. K. , Levesque B. G. , Feagan B. G.
Published: May 2016

Background

Matrix metalloproteinase‐9 is a proteolytic enzyme whose expression is increased in ulcerative colitis.

Aim

To evaluate the safety and efficacy of GS‐5745, a fully humanised anti‐matrix metalloproteinase‐9 monoclonal antibody, in moderately‐to‐severely active ulcerative colitis.

Methods

We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS‐5745 or placebo. Multiple‐dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS‐5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS‐5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS‐5745. Exploratory analyses in the multiple‐dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS‐5745 were explored using histological and molecular approaches.

Results

Twenty‐three of the 42 patients (55%) receiving multiple doses of GS‐5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS‐5745 showed target‐mediated drug disposition, approximately dose‐proportional increases in maximum plasma concentration and more than dose‐proportional increases in the area under the plasma drug concentration‐time curve. Clinical response occurred in 18/42 patients (43%) receiving GS‐5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS‐5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS‐5745 had reductions in matrix metalloproteinase‐9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0.008) significant improvements in histopathology scores (confirmed with three separate histological disease activity indices), as well as changes in colonic gene expression that were consistent with reduced inflammation.

Conclusion

This phase 1 trial provides preliminary evidence for the safety and therapeutic potential of GS‐5745 in the treatment of ulcerative colitis.
Visfatin Triggers the Cell Motility of Non‐Small Cell Lung Cancer via Up‐Regulation of Matrix Metalloproteinases
Authors: Wang Guanghai , Tian Wenjun , Liu Yiqing , Ju Ying , Shen Yajuan , Zhao Shengmei , Zhang Bingchang , Li Yu
Published: May 2016

High levels of visfatin are correlated with worse clinical prognosis of various cancers. Still, the effects and mechanisms of visfatin on progression of non‐small cell lung cancer (NSCLC) remain unclear. This study revealed that plasma levels of visfatin in patients with NSCLC (585 ± 287 pg/ml) were significantly (p < 0.01) higher than those in healthy people (142 ± 61.1 pg/ml). The high level of plasma visfatin was found to be significantly (p < 0.05) correlated with TNM stage, lymph node metastasis and distant metastasis. Visfatin treatment can increase the migration and invasion of NSCLC cells via up‐regulation of metalloproteinase‐2 (MMP‐2) and MMP‐9. Both si‐MMP‐2 and si‐MMP‐9 attenuated visfatin‐induced migration of NSCLC cells. The inhibitor of NF‐κB, while not ERK1/2, p38‐MAPK or PI3K/Akt, can significantly abolish visfatin‐induced migration of A549 cells and up‐regulation of MMP‐2 and MMP‐9. Furthermore, visfatin can increase the phosphorylation of IκBα and p65 and the transcription activities of NF‐κB in NSCLC cells. ACHP, the inhibitor of IKK‐β, blocked visfatin‐induced activation of p65 and up‐regulation of MMP‐2 and MMP‐9. Collectively, our data revealed that visfatin can trigger the in vitro migration and invasion of NSCLC cells via up‐regulation of MMPs through activation of NF‐κB.
Loss of PUMA (BBC3) does not prevent thrombocytopenia caused by the loss of BCL‐XL (BCL2L1)
Authors: Delbridge Alex R. D. , Chappaz Stephane , Ritchie Matthew E. , Kile Benjamin T. , Strasser Andreas , Grabow Stephanie
Published: May 2016

Apoptosis is required to maintain tissue homeostasis in multicellular organisms. Platelets, the anucleate cells that are essential for blood clotting, are a prime example. Their brief life span in the circulation is regulated by the intrinsic apoptosis pathway. Pro‐survival BCL‐XL (also termed BCL2L1) is essential for platelet viability. It functions to restrain the pro‐apoptotic BCL‐2 family members BAK (also termed BAK1) and BAX, the essential mediators of intrinsic apoptosis. Genetic deletion or pharmacological inhibition of BCL‐XL results in thrombocytopenia. Conversely, deletion of BAK in platelets doubles their circulating life span. However, what triggers platelet apoptosis in vivo remains unclear. The pro‐apoptotic BH3‐only proteins are essential for initiating apoptosis in nucleated cells, and there is some evidence to suggest they also play a role in platelet biology. We investigated whether PUMA (also termed BBC3), a potent BH3‐only protein that can inhibit all pro‐survival BCL‐2 family members as well as directly activate BAX, regulates the death of platelets. Surprisingly, loss of PUMA had no impact on the loss of platelets caused by loss of BCL‐XL. It therefore remains to be established whether other BH3‐only proteins play a critical role in induction of apoptosis in platelets or whether their death is controlled solely by the interactions between BCL‐XL with BAK and BAX.
Cumulative, Timing‐Specific, and Interactive Models of Residential Mobility and Children's Cognitive and Psychosocial Skills
Authors: Coley Rebekah Levine , Kull Melissa
Published: May 2016

Residential mobility has received notable attention in the literature, yet there remains limited consensus on how and when mobility is associated with detriments to children's development. Drawing on a nationally representative sample of 19,162 children in the Early Childhood Longitudinal Study followed from kindergarten through eighth grade, this study compared cumulative, timing‐specific, and interactive models of mobility. Results found that mobility during middle childhood and early adolescence was negatively associated with children's cognitive skills, with short‐term effects that dissipated over time. In contrast, associations with psychosocial functioning emerged in relation to early and middle childhood mobility. Effects of residential mobility were robust to more conservative modeling techniques and adjustments for school mobility.
Genetic, epidemiologic and clinicopathologic studies of Japanese Asian patients with Birt–Hogg–Dubé syndrome
Authors: Furuya Mitsuko , Yao Masahiro , Tanaka Reiko , Nagashima Yoji , Kuroda Naoto , Hasumi Hisashi , Baba Masaya , Matsushima Jun , Nomura Fumio , Nakatani Yukio
Published: May 2016

Birt–Hogg–Dubé syndrome (BHD) is a rare genetic disorder characterized by fibrofolliculomas, pulmonary cysts and renal cell carcinomas (RCCs). The affected individuals inherit germline mutations in the folliculin gene (FLCN). We investigated the mutation spectrum and clinicopathologic findings of 312 patients from 120 different families (119 Japanese and 1 Taiwanese). A total of 31 different FLCN sequence variants were identified. The majority were c.1285dupC (n = 34), c.1533_1536delGATG (n = 25), and c.1347_1353dupCCACCCT (n = 19). Almost all patients presented with pulmonary cysts. The incidence of RCCs in FLCN mutation carriers over the age of 40 was 34.8% (40/115). Fifty‐five RCC lesions were surgically resected; most were either chromophobe RCC (n = 24; 43.6%) or hybrid oncocytic/chromophobe tumors (19; 34.5%). Seventy‐six of 156 FLCN mutation carriers (120 probands and 36 sibs, 48.7%) had skin papules; however, cutaneous manifestations were so subtle that only one patient voluntarily consulted dermatologists. Japanese Asian BHD families have three FLCN mutational hotspots. Recurrent episodes of pneumothoraces are the major symptoms suggestive of a BHD diagnosis in our cohort. Characteristic features of lung and kidney lesions may be more informative than fibrofolliculomas as diagnostic criteria for BHD in the Japanese Asian population.
Convolutional Sparse Coding for High Dynamic Range Imaging
Authors: Serrano Ana , Heide Felix , Gutierrez Diego , Wetzstein Gordon , Masia Belen
Published: May 2016

Current HDR acquisition techniques are based on either (i) fusing multibracketed, low dynamic range (LDR) images, (ii) modifying existing hardware and capturing different exposures simultaneously with multiple sensors, or (iii) reconstructing a single image with spatially‐varying pixel exposures. In this paper, we propose a novel algorithm to recover high‐quality HDRI images from a single, coded exposure. The proposed reconstruction method builds on recently‐introduced ideas of convolutional sparse coding (CSC); this paper demonstrates how to make CSC practical for HDR imaging. We demonstrate that the proposed algorithm achieves higher‐quality reconstructions than alternative methods, we evaluate optical coding schemes, analyze algorithmic parameters, and build a prototype coded HDR camera that demonstrates the utility of convolutional sparse HDRI coding with a custom hardware platform.
Roles of FGFR in oral carcinogenesis
Authors: Xie Xiaoyan , Wang Zhiyong , Chen Fangman , Yuan Yao , Wang Jiayi , Liu Rui , Chen Qianming
Published: May 2016

Fibroblast growth factor receptors (FGFRs) play essential roles in organ development during the embryonic period, and regulate tissue repair in adults. Accumulating evidence suggests that alterations in FGFR signalling are involved in diverse types of cancer. In this review, we focus on aberrant regulation of FGFRs in pathogenesis of oral squamous cell carcinoma (OSCC), including altered expression and subcellular location, aberrant isoform splicing and mutations. We also provide an overview of oncogenic roles of each FGFR and its downstream signalling pathways in regulating OSCC cell proliferation and metastasis. Finally, we discuss potential application of FGFRs as anti‐cancer targets in the preclinical environment and in clinical practice.
Pharmacokinetics of prolonged‐release tacrolimus and implications for use in solid organ transplant recipients
Authors: Tanzi Maria G. , Undre Nasrullah , Keirns James , Fitzsimmons William E. , Brown Malcolm , First M. Roy
Published: May 2016

Prolonged‐release tacrolimus was developed as a once‐daily formulation with ethylcellulose as the excipient, resulting in slower release and reduction in peak concentration (Cmax) for a given dose compared with immediate‐release tacrolimus, which is administered twice daily. This manuscript reviews pharmacokinetic information on prolonged‐release tacrolimus in healthy subjects, in transplant recipients converted from immediate‐release tacrolimus, and in de novo kidney and liver transplant recipients. As with the immediate‐release formulation, prolonged‐release tacrolimus shows a strong correlation between trough concentration (Cmin) and area under the 24‐hour time–concentration curve (AUC24), indicating that trough whole blood concentrations provide an accurate measure of drug exposure. We present the pharmacokinetic similarities and differences between the two formulations, so that prescribing physicians will have a better understanding of therapeutic drug monitoring in patients receiving prolonged‐release tacrolimus.
What information about donation after circulatory death is available on the Internet for potential donor families?
Authors: Black Kristin , Miller Katherine , Beck Gavin , Moser Michael
Published: May 2016

Introduction

The purpose of this study is to determine what information about donation after circulatory death (DCD) is available on the Internet and to document the common statements for and against DCD.

Methods

The search terms non‐heart‐beating donor, donation after cardiac death, DCD, deceased donor, organ donation, and organ harvesting were entered into the four most‐accessed English‐language Internet search engines. The top 10 webpages from each search (240 webpages) yielded 116 unique sites. Three reviewers reviewed each webpage and recorded statements for and against DCD as well as site type, tone, and mention of DCD.

Results

While 59 (50.9%) of the overall 116 sites included DCD information, only 10% of sites found with the term “organ donation” mentioned DCD at all. The sites that did include DCD were mostly (78%) of the type “medical journal” or “hospital or university webpage” and 89% of these had a positive or neutral tone. Nine positive and nine negative tropes were defined using the Grounded Theory Method.

Conclusion

This study reveals the lack of information regarding DCD in organ donation webpages. Thoughtful responses to these statements should be considered in family discussions and in the design of future webpages.
Pancreatic cytology: standardised terminology and nomenclature
Authors: Perez‐Machado M. A.
Published: May 2016

Pancreatic cytology can make a real difference to the management of patients. However it is a challenge in those cases where a definitive diagnosis of malignancy cannot be made with confidence. This creates the need for a unified terminology and nomenclature system that provides intra‐ and interdepartmental guidance for diagnosis. The Papanicolaou Society of Cytopathology (PSC) has published new guidelines for pancreaticobiliary cytology, addressing indications, techniques, terminology and nomenclature, ancillary studies, and postprocedure management.
Linking Electronic Medical Records Use to Physicians’ Performance: A Contextual Analysis
Authors: Dobrzykowski David D. , Tarafdar Monideepa
Published: May 2016

Electronic Medical Records (EMR) studies have broadly tested EMR use and outcomes, producing mixed and inconclusive results. This study carefully considers the healthcare delivery context and examines relevant mediating variables. We consider key characteristics of: (i) interdependence in healthcare delivery processes, (ii) physician autonomy, and (iii) the trend of hospital employment of physicians, and draw on theoretical perspectives in coordination, shared values, and agency to explain how the use of EMR can improve physicians’ performance. In order to examine the effects of physician employment on work practices in the hospital, we collected 583 data points from 302 hospitals in 47 states in the USA to test two models: one for employed and another for nonemployed physicians. Results show that information sharing and shared values among healthcare delivery professionals fully mediate the relationship between EMR use and physicians’ performance. Next, physician employment determines which mediating variable constitutes the pathway from EMR use to physicians’ performance. Finally, we highlight the impact of shared values between the hospital and physicians in enhancing information sharing and physicians’ performance, extending studies of these behaviors among network partners in industrial settings. Overall, our study shows that EMR use should be complemented by processual (information sharing), social (shared values), and structural (physician employment) mechanisms to yield positive effects on physicians’ performance.
Sociology of the Veil in Saudi Arabia: Dress Code, Individual Choices, and Questions on Women's Empowerment
Authors: Quamar Md. Muddassir
Published: May 2016

Veiling is commonly practiced in many Muslim societies, but its prevalence, and enforcement in Saudi Arabia is extraordinary. With changing status, Saudi women have started to defy the practice; and it is suggested that its enforcement has also become less frequent. In contemporary Saudi Arabia, many women, following the dress code of theabaya(black cloak) andhijab(head cover), have started to discard thenaqab(face veil). Does this indicate a widening of the margins so far as veiling is concerned? Or is it an indication that Saudi society is becoming amenable to individual choices? To conclude that veiling has become a matter of individual choice would stretch the point beyond fact, but suggesting diversity in veiling practice would not be wrong. Saudi women continue to face structural constraints and systemic discrimination, but their improving socioeconomic conditions have provided them the ability to choose the way they want to be dressed in public so far as the use of naqab is concerned. Though a minor development, contextualized in the larger discourse on women's empowerment, this is no small achievement and is indicative of ruptures in the established social norm of veiling.
Plant defense responses induced by Bemisia tabaci Middle East—Asia Minor 1 salivary components
Authors: Yan Ying , Zhang HaiJing , Yang YiTing , Zhang Yan , Guo JianYang , Liu WanXue , Wan FangHao
Published: May 2016

The in vivo effects of Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) Middle East—Asia Minor 1 (MEAM1) saliva on the induced defense of tomato plants were examined. After infiltration of MEAM1 saliva into tomato leaves, qPCR analysis indicated strong local induction of salicylic acid (SA)‐responsive genes — salicylic acid induction deficient 2 (SID2) and β‐1,3‐glucanase (BGL2)— whereas pathogenesis‐related protein‐1 (PR1) showed strong induction both locally and systemically. The jasmonic acid (JA)‐responsive genes — omega‐3 fatty acid desaturase 3 (FAD3), lipoxygenase (LOX), and proteinase inhibitor II (PI‐II) — indicated moderate induction both locally and systemically. The activities of peroxidases and catalase were also induced both locally and systemically, whereas polyphenol oxidase and lipoxygenase were either transiently induced or unchanged. When either MEAM1 or AsiaII_3 whitefly adults were given access to leaves 2 h after saliva infiltration, the number of F1 progeny on the leaves on which the infiltration took place was significantly reduced for both. In contrast, when either MEAM1 or AsiaII_3 adults were given access to leaves 1 day after infiltration, the number of AsiaII_3 progeny was significantly reduced, whereas the number of MEAM1 progeny remained the same as the control. After 2 days, there was no significant difference for the infiltrated leaves for either species. In contrast, 2 h, 1 day, and 2 days after saliva infiltration, the number of F1 MEAM1 progeny on leaves where infiltration did not take place was the same as the controls, whereas the number of AsiaII_3 progeny was significantly reduced. Furthermore, the percentage of MEAM1 adults on leaves with high PR1 and BGL2 RNAs was significantly higher than the percentage of AsiaII_3 adults. Altogether, infiltration of MEAM1 saliva caused intense local defense, as well as moderate, but more persistent systemic defense. Both the SA and JA signaling pathways were regulated by MEAM1 salivary components, and were associated with asymmetric plant defense that favored MEAM1 over AsiaII_3.