bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Supply Management: The Basis for Professional Development
Authors: Reck Robert F. , Landeros Robert , Lyth David M.
Published: June 2017

Purchasing and materials management has undergone dramatic changes in the last few decades—moving from a reactive activity to a strategic one, contributing to a firm's competitive success. The skills and competencies required by professionals in the past are not the same as those required today, nor will today's be sufficient in the future. However, the skills and competencies needed today provide a starting point from which to project those that will be needed in the twenty‐first century. This study reports on the skills and competencies that were identified by purchasing and materials management executives in 23 major industrial corporations. Their perspective should be beneficial in identifying specific areas to emphasize in university purchasing and materials management curricula and in company training programs. The results of this study are not revolutionary, but evolutionary, in nature and hold several implications for purchasing and materials management educators.
The highly pathogenic H5N1 influenza A virus down‐regulated several cellular MicroRNAs which target viral genome
Authors: Wang Rong , Zhang Ying‐Ying , Lu Jian‐Sheng , Xia Bing‐Hui , Yang Zhi‐Xin , Zhu Xu‐Dong , Zhou Xiao‐Wei , Huang Pei‐Tang
Published: June 2017

Higher and prolonged viral replication is critical for the increased pathogenesis of the highly pathogenic avian influenza (HPAI) subtype of H5N1 influenza A virus (IAV) over the lowly pathogenic H1N1 IAV strain. Recent studies highlighted the considerable roles of cellular miRNAs in host defence against viral infection. In this report, using a 3′UTR reporter system, we identified several putative miRNA target sites buried in the H5N1 virus genome. We found two miRNAs, miR‐584‐5p and miR‐1249, that matched with the PB2 binding sequence. Moreover, we showed that these miRNAs dramatically down‐regulated PB2 expression, and inhibited replication of H5N1 and H1N1 IAVs in A549 cells. Intriguingly, these miRNAs expression was differently regulated in A549 cells infected with the H5N1 and H1N1 viruses. Furthermore, transfection of miR‐1249 inhibitor enhanced the PB2 expression and promoted the replication of H5N1 and H1N1 IAVs. These results suggest that H5N1 virus may have evolved a mechanism to escape host‐mediated inhibition of viral replication through down‐regulation of cellular miRNAs, which target its viral genome.
MiR‐29b‐3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN
Authors: Chen Lingqiang , Li Qin , Wang Jing , Jin Song , Zheng Hongmei , Lin Jun , He Fang , Zhang Hong , Ma Sha , Mei Jian , Yu Juan
Published: June 2017

This study was aimed to explore the role of miR‐29b‐3p and PGRN in chondrocyte apoptosis and the initiation and progress of osteoarthritis (OA). Both miR‐29b‐3p and PGRN were up‐regulated in cartilage tissue from patients with OA. Transfection of miR‐29b‐3p mimic into rat primary chondrocytes and SW1353 chondrosarcoma cells significantly suppressed PGRN expression and release, induced apoptosis, inhibited proliferation and scratch wound closure. By contrast, transfection of miR‐29b‐3p inhibitor exhibited the opposite effects. Moreover, the expression and secretion of cartilaginous degeneration‐related molecules were also altered by miR‐29b‐3p. Luciferase reporter gene assay showed rat GRN mRNA is directly targeted and repressed by miR‐29b‐3p. The fact that recombinant PGRN or shPGRN‐mediated PGRN interference abolished miR‐29b‐3p mimic‐induced cell apoptosis and growth inhibition suggested miR‐29b‐3p affect the cellular functions of chondrocyte through regulating PGRN expression. In vivo, joint cavity injection of miR‐29b‐3p antagomir prior to surgical induction of OA significantly suppressed the upregulation of miR‐29b‐3p, whereas further promoted the increased expression of PGRN. Articular chondrocytes apoptosis and cartilage loss in the knee joint of surgically induced OA rats were also ameliorated by the injection of miR‐29b‐3p antagomir, demonstrated by TUNEL and safranin O‐fast green staining. This work showed miR‐29b‐3p facilitates chondrocyte apoptosis and OA by targeting PGRN, and miR‐29b‐3p or PGRN may be the potential target for OA treatments.
iPSC technology‐based regenerative therapy for diabetes
Authors: Kondo Yasushi , Toyoda Taro , Inagaki Nobuya , Osafune Kenji
Published: June 2017

The directed differentiation of human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), into pancreatic endocrine lineages has been vigorously examined by reproducing the in vivo developmental processes of the pancreas. Recent advances in this research field have enabled the generation from hESCs/iPSCs of functionally mature β‐like cells in vitro that show glucose‐responsive insulin secretion ability. The therapeutic potentials of hESC/iPSC‐derived pancreatic cells have been evaluated using diabetic animal models, and transplantation methods including immunoprotective devices that prevent immune responses from hosts to the implanted pancreatic cells have been investigated towards the development of regenerative therapies against diabetes. These efforts led to the start of a clinical trial that involves the implantation of hESC‐derived pancreatic progenitors into type 1 diabetes patients. In addition, patient‐derived iPSCs have been generated from diabetes‐related disorders towards the creation of novel in vitro disease models and drug discovery, although few reports so far have analyzed the disease mechanisms. Considering recent advances in differentiation methods that generate pancreatic endocrine lineages, we will see the development of novel cell therapies and therapeutic drugs against diabetes based on iPSC technology‐based research in the next decade.
Psoriasis in Latin America and the Caribbean: a systematic review
Authors: Hernández‐Vásquez A. , Molinari L. , Larrea N. , Ciapponi A.
Published: June 2017

Psoriasis is a chronic inflammatory disease that generally affects the skin, nails and joints. The burden of psoriatic disease in Latin America and the Caribbean (LAC) remains largely unknown. To estimate the burden of psoriasis in LAC. We conducted a systematic review following the MOOSE and PRISMA statements. We searched published studies in MEDLINE, EMBASE, LILACS and CENTRAL from 1st January 2000 to 5th August 2015. We included studies that reported incidence, prevalence, health resource use and health expenditures, treatment patterns, comparative effectiveness of different drugs, patients reported outcomes, adherence to treatment and patient preferences in LAC. Risk of bias was assessed evaluating selection of participants, control of cofounders, measurement of exposure and outcome and conflict of interest. Pairs of reviewers independently selected, extracted and assessed the bias risk of the studies. The systematic review was registered at PROSPERO (CRD42016038325). A total of 18 studies from 12 LAC countries were included. Most were observational studies, between which there was a large heterogeneity of outcomes. Population‐based studies were not found and most data came from hospital registries. One study reported an incidence of psoriatic arthritis in 6.26 cases per 100 000 person‐years. Another study found an incidence of psoriasis 1020 per 100 000 patient‐year attending at a dermatology clinic. The prevalence reported in the Argentinean health service was 74 cases per 100 000. Further, psoriasis has been shown to have a substantial negative impact on quality of life. A number of studies also indicated that non‐communicable disease burden increases with the presence and severity of psoriasis. With regard to treatment pattern, methotrexate was the dominant systemic therapy. In conclusion, there is an important lack of information from LAC concerning the burden of psoriasis. Further studies investigating the burden of psoriasis in representative LAC populations are needed.
Psoriasis comorbidity affects multiple sclerosis neurological progression: a retrospective case – control analysis
Authors: Miron G. , Gurevich M. , Baum S. , Achiron A. , Barzilai A.
Published: June 2017

Background

Multiple sclerosis (MS) and psoriasis are inflammatory disorders, with epidemiological and biological associations. The impact of one disease on the course of the other has not been studied.

Objective

To characterize patients with psoriasis and MS, and to assess whether psoriasis comorbidity affected the progression of MS.

Methods

A retrospective case–control study. Patients with psoriasis comorbidity were identified from 3456 patients included in the Sheba Hospital Multiple Sclerosis Center database. Clinical and demographical characteristics and MS progression‐related outcomes in patients whose follow‐up exceeded 5 years were analysed and compared to those of a matched control cohort of MS‐only (MSO) patients.

Results

Forty‐five (1.3%) MS patients had psoriasis comorbidity. Psoriasis preceded MS in 35 (78%) cases. The psoriasis was defined as mild, moderate and severe in 24 (53%), twelve (27%) and nine (20%) cases respectively. MS progression‐related outcomes were evaluated in 35 patients that had follow‐up over 5 years. Patients with psoriasis onset preceding relapsing‐remitting MS (RRMS) had slower progression of disease compared to MSO patients, as manifested by a longer time to second relapse (P < 0.01) and a longer time to significant neurological disability scores (P < 0.03).

Conclusion

Psoriasis comorbidity preceding the onset of MS is associated with slower progression of disability.
Effect of etching on bonding of a self‐etch adhesive to dentine affected by amelogenesis imperfecta
Authors: Epasinghe Don Jeevanie , Yiu Cynthia Kar Yung
Published: June 2017

Aim

Dentine affected by amelogenesis imperfecta (AI) is histologically altered due to loss of hypoplastic enamel and becomes hypermineralized. In the present study, we examined the effect of additional acid etching on microtensile bond strength of a self‐etch adhesive to AI‐affected dentine.

Methods

Flat coronal dentine obtained from extracted AI‐affected and non‐carious permanent molars were allocated to two groups: (a) Clearfil SE Bond (control); and (b) Clearfil SE Bond and additional etching with 34% phosphoric acid for 15 seconds. The bonded teeth were sectioned into .8‐mm2 beams for microtensile bond strength testing, and stressed to failure under tension. The bond strength data were analyzed using two‐way analysis of variance (dentine type and etching step) and Student‐Newman‐Keuls multiple comparison test (P<.05). Representative fractured beams from each group were examined under scanning electron microscopy.

Results

Both factors, dentine substrate (P<.001) and etching step (P<.05), and their interactions (P<.001), were statistically significant. Additional etching had an adverse effect on the bond strength of Clearfil SE Bond to normal dentine (P<.005), and no significant improvement was found for AI‐affected dentine (P=.479).

Conclusion

Additional acid etching does not improve the bond strength of a self‐etch adhesive to AI‐affected dentine.
Theorizing Reciprocity: Andean Cooperation and the Reproduction of Community in Highland Bolivia
Authors: Walsh‐Dilley Marygold
Published: June 2017

Los estudios andinos han sido cuajado, en gran parte, por la noción compartida de la reciprocidad como un elemento central de la cultura indígena andina, y la reciprocidad (ayni) continúa ser tanto como una práctica activa de las comunidades andinas y una forma idealizada en los movimientos políticos contemporáneos. Sin embargo, los usos de ayni en los discursos politicos contemporáneos han sido criticadas fuertemente como esencialista, estático y anticuado. En este trabajo, se propone una nueva teorización de la reciprocidad andina como una práctica económica‐moral‐simbólico que se reproduce socialmente a través de las prácticas cotidiana. Re‐imaginando la reciprocidad de esta manera nos permite ver cómo la reciprocidad andina es una forma de interración dinámica y cambiante que sirve los propósitos éticos, simbólicos y económicos, y por lo tanto evita tratar la reciprocidad andina como un artefacto tradicional. Basándose en extenso trabajo de campo etnográfico en tres comunidades del altiplano boliviano, este trabajo propone que la interacción recíproca constituye un sitio importante donde las comunidades andinas sean reproducido.
Formation and preservation of fresh lawsonite: Geothermobarometry of the North Makran Blueschists, southeast Iran
Authors: Hunziker D. , Burg J.‐P. , Moulas E. , Reusser E. , Omrani J.
Published: June 2017

A low‐grade metamorphic “Coloured Mélange” in North Makran (SE Iran) contains lenses and a large klippe of low temperature, lawsonite‐bearing blueschists formed during the Cretaceous closure of the Tethys Ocean. The largest blueschist outcrop is a >1,000 m thick coherent unit with metagabbros overlain by interlayered metabasalts and metavolcanoclastic rocks. Blueschist metamorphism is only incipient in coarse‐grained rocks, whereas finer grained, foliated samples show thorough metamorphic recrystallization. The low‐variance blueschist peak assemblage is glaucophane, lawsonite, titanite, jadeite±phengitic mica. Investigated phase diagram sections of three blueschists with different protoliths yield peak conditions of ~300–380°C at 9–14 kbar. Magnesio‐hornblende and rutile cores indicate early amphibolite facies metamorphism at >460°C and 2–4 kbar. Later conditions at slightly higher pressures of 6–9 kbar at 350–450°C are recorded by barroisite, omphacite and rutile assemblages before entering into the blueschist facies and finally following a retrograde path through the pumpellyite–actinolite facies across the lawsonite stability field. Assuming that metamorphic pressure is lithostatic pressure, the corresponding counterclockwise P–T path is explained by burial along a warm geothermal gradient (~15°C/km) in a young subduction system, followed by exhumation along a cold gradient (~8°C/km); a specific setting that allows preservation of fresh undecomposed lawsonite in glaucophane‐bearing rocks.
Taxation in digital media markets
Authors: Kind Hans Jarle , Koethenbuerger Marko
Published: June 2017

Digital media goods and digital media platforms exhibit cost structures and network effects that might imply that price and quantity effects of consumption taxes are qualitatively different compared to what we typically find for physical goods. For instance, in most European countries and U.S. states, printed newspapers and books face favorable value added taxes (VATs) or sales taxes. This has probably increased their circulation. In contrast, reducing the VAT rate on digital newspapers has the opposite effects; it increases prices and leads to lower sales. This is not true for ebooks, but a low‐tax policy is still ineffective if the aim is to reduce prices. The primary effect of exempting ebooks from VATs is to increase profits for publishers.
Testing the Efficiency of the Art Market Using Quantile‐Based Unit Root Tests with Sharp and Smooth Breaks
Authors: Aye Goodness C. , Chang Tsang Yao , Chen Wen‐Yi , Gupta Rangan , Wohar Mark
Published: June 2017

This paper examines the efficiency market hypothesis for the art market using a novel nonlinear quantile‐based unit root test while accounting for sharp shifts and smooth breaks in the data. We use quarterly data which covers 1998:1 and 2015:1. Our analysis is based on 15 art price indices: Contemporary, Drawings, France, Global index (Euro), Global index (USD), Modern art, Nineteenth century, Old Masters, Paintings, Photographies, Postwar, Prints, Sculptures, UK and US. We find evidence of structural shifts and nonlinearity in the art indices. We cannot reject the null of unit root and/or stationarity in the art series based on the conventional linear unit root tests and quantile‐based test that did not account for structural breaks. However, when we use the same methods but accounting for sharp shifts and smooth breaks, we are able to reject the unit root null for each of the art indices. Further we find evidence of asymmetric behaviour in some of the indices: two global indices, Paintings, Prints, Sculptures, Modern art and Postwar, where unit root exist at some quantiles but not at others. Overall, our result suggest that the art market is inefficient. We provide some practical and policy implications of our findings.
Targeted antimicrobial therapy in the microbiome era
Authors: Stone V.N. , Xu P.
Published: June 2017

Even though the oral microbiome is one of the most complex sites on the body it is an excellent model for narrow‐spectrum antimicrobial therapy. Current research indicates that disruption of the microbiome leads to a dysbiotic environment allowing for the overgrowth of pathogenic species and the onset of oral diseases. The gram‐negative colonizer, Porphyromonas gingivalis has long been considered a key player in the initiation of periodontitis and Streptococcus mutans has been linked to dental caries. With antibiotic research still on the decline, new strategies are greatly needed to combat infectious diseases. By targeting key pathogens, it may be possible to treat oral infections while allowing for the recolonization of the beneficial, healthy flora. In this review, we examine unique strategies to specifically target periodontal pathogens and address what is needed for the success of these approaches in the microbiome era.
Automated identification of sugar beet diseases using smartphones
Authors: Hallau L. , Neumann M. , Klatt B. , Kleinhenz B. , Klein T. , Kuhn C. , Röhrig M. , Bauckhage C. , Kersting K. , Mahlein A.‐K. , Steiner U. , Oerke E.‐C.
Published: June 2017

Cercospora leaf spot (CLS) poses a high economic risk to sugar beet production due to its potential to greatly reduce yield and quality. For successful integrated management of CLS, rapid and accurate identification of the disease is essential. Diagnosis on the basis of typical visual symptoms is often compromised by the inability to differentiate CLS symptoms from similar symptoms caused by other foliar pathogens of varying significance, or from abiotic stress. An automated detection and classification of CLS and other leaf diseases, enabling a reliable basis for decisions in disease control, would be an alternative to visual as well as molecular and serological methods. This paper presents an algorithm based on a RGB‐image database captured with smartphone cameras for the identification of sugar beet leaf diseases. This tool combines image acquisition and segmentation on the smartphone and advanced image data processing on a server, based on texture features using colour, intensity and gradient values. The diseases are classified using a support vector machine with radial basis function kernel. The algorithm is suitable for binary‐class and multi‐class classification approaches, i.e. the separation between diseased and non‐diseased, and the differentiation among leaf diseases and non‐infected tissue. The classification accuracy for the differentiation of CLS, ramularia leaf spot, phoma leaf spot, beet rust and bacterial blight was 82%, better than that of sugar beet experts classifying diseases from images. However, the technology has not been tested by practitioners. This tool can be adapted to other crops and their diseases and may contribute to improved decision‐making in integrated disease control.
Organizational Response to Changing Demands: Predicting Behavior in Donor Networks
Authors: AbouAssi Khaldoun , Tschirhart Mary
Published: June 2017

The integration of resource dependence theory and a network perspective results in a parsimonious “strategic response model” for the organizational responses of exit, voice, loyalty, and adjustment. Four cases illustrate the model's application to nonprofit organizations by focusing on relations with a government aid agency that switched funding priorities. The model helps explain why networks of recipients of funding may change over time and predicts organizational responses to changing demands from resource providers.
Occupation Coding During the Interview
Authors: Schierholz Malte , Gensicke Miriam , Tschersich Nikolai , Kreuter Frauke
Published: June 2017

Currently, most surveys ask for occupation with open-ended questions. The verbal responses are coded afterwards, which is error prone and expensive. We present an alternative approach that allows occupation coding during the interview. Our new technique uses a supervised learning algorithm to predict candidate job categories. These suggestions are presented to the respondent, who in turn can choose the most appropriate occupation. 72.4% of the respondents selected an occupation when the new instrument was tested in a telephone survey, entailing potential cost savings. To aid further improvements, we identify some factors for how to increase quality and to reduce interview duration.
Role of vascular calcification inhibitors in preventing vascular dysfunction and mortality in hemodialysis patients
Authors: Gungor Ozkan , Kocyigit Ismail , Yilmaz Mahmut Ilker , Sezer Siren
Published: June 2017

Cardiovascular events make up the primary cause of death in hemodialysis patients, and the risk for cardiovascular mortality is significantly increased by vascular calcification, a condition observed frequently in this patient population. The mechanisms underlying the pathogenesis of vascular calcification are complex, and many factors facilitate or hinder the development of calcification. In this review, we first summarize the main factors contributing to the pathogenesis of vascular calcification in patients with end‐stage renal disease. We then explore the role of calcification inhibitors in the calcification process, as well as their effect on vascular dysfunction and mortality in hemodialysis patients.
The Rise of Han‐Centrism and What It Means for International Politics
Authors: Friend John M. , Thayer Bradley A.
Published: June 2017

This article addresses the rise of Han‐centrism, a form of hyper‐nationalism, in contemporary China. As Chinese nationalism has become more ethnocentric since the 1990s, the cultural chauvinism of Han‐centrism has become increasingly more influential in the debate over national identity. Within this narrative, Han culture is considered to be the authentic character of the nation; to deviate from the Han identity will only tarnish Chinese exceptionalism and impede China's rise. While Chinese nationalism consists of many competing discourses, we argue that Han‐centrism has a significant influence within both policy‐making circles and the public sphere in China, and, as a result, has important consequences for the future of international politics.
Configuring Catholicism in the anthropology of Christianity
Authors: Brown Bernardo , Feener R. Michael
Published: June 2017

In order to better understand diverse configurations of Catholicism in relation to the contemporary anthropology of Christianity, we need to develop more dynamic models to interpret the interaction between the material of particular ethnographic accounts and the continual recalibration of broader cultural and theological paradigms involved in their framing and analysis. Building upon the growing body of work that has been produced in both the ethnography of Catholic communities and the critical reflection on theoretical dimensions of the new project of the anthropology of Christianity, we hope to nudge conversations toward more integrated explorations between these two lines of enquiry. The research presented in the articles included in this special issue collectively suggests that turning the ethnographic lens toward Asian Catholicism can serve to substantially enrich conversations with new empirical material on modern forms of religiosity. Well beyond that, moreover, critical engagement with such dynamic, theologically sophisticated, aesthetically complex, and socially engaged traditions can inform constructive critiques of the mainstream account of Anthropology's approach to the study of Christianity.
The interaction between individual, social and environmental factors and their influence on dietary intake among adults in Toronto
Authors: Liadsky Daniel , Ceh Brian
Published: June 2017

Health outcomes related to vegetable and fruit consumption are widely recognized in the literature. This study investigates how dietary intake is influenced by individual, social, and environmental factors in the Toronto Census Metropolitan Area. The analysis and findings are based on data from the Canadian Community Health Survey which provides self‐reported vegetable and fruit intake from 6,513 adults in 2009‐2010. Food environment measures were constructed from commercial databases using kernel density estimates and network drive times. Spatial and multivariable techniques were used to determine the associations between diet, the food environment, and other health and socioeconomic factors. Particular emphasis was given to understanding the interaction between the food environment and socioeconomic position. Unexpectedly, supermarket density was found to have an inverse association with vegetable and fruit intake. Interaction terms for individuals with low income and reduced mobility produced different responses in men and women, confirming that the influence of the food environment is not uniform for all subgroups.
Apoptotic intrinsic pathway proteins predict survival in canine cutaneous mast cell tumours
Authors: Barra C. N. , Macedo B. M. , Cadrobbi K. G. , Pulz L. H. , Huete G. C. , Kleeb S. R. , Xavier J. G. , Catão‐Dias J. L. , Nishiya A. T. , Fukumasu H. , Strefezzi R. F.
Published: June 2017

Mast cell tumours (MCTs) are the most frequent canine round cell neoplasms and show variable biological behaviours with high metastatic and recurrence rates. The disease is treated surgically and wide margins are recommended. Adjuvant chemotherapy and radiotherapy used in this disease causeDNAdamage in neoplastic cells, which is aimed to induce apoptotic cell death. Resisting cell death is a hallmark of cancer, which contributes to the development and progression of tumours. The aim of this study was to investigate the expression of the proteins involved in the apoptotic intrinsic pathway and to evaluate their potential use as prognostic markers for canine cutaneousMCTs. Immunohistochemistry forBAX,BCL2,APAF1, Caspase‐9, and Caspase‐3 was performed in 50 canine cases ofMCTs. HighBAXexpression was associated with higher mortality rate and shorter survival.BCL2andAPAF1expressions offered additional prognostic information to the histopathological grading systems. The present results indicate that variations in the expression of apoptotic proteins are related to malignancy of cutaneous MCTs in dogs.
The road disturbance attenuation for quarter car active suspension system via a new static two-degree-of-freedom design
Authors: Altun Yusuf
Published: June 2017

The main aim of this paper is to attenuate the effects of the road disturbance on the quarter-car active suspension system (ASS) for the passenger comfort by using design. Therefore, a new static disturbance compensator is proposed by using linear matrix inequality method such that the disturbance compensator and feedback controller are simultaneously designed for the disturbances in the linear time-invariant systems, which are measurable or predictable. They have static structure, and the disturbance compensator is designed on the feedforward path. The design is applied against the road disturbance affecting the quarter car ASS. The effectiveness of the design is demonstrated with the simulations.
Effects of ultraviolet and vacuum ultraviolet synchrotron radiation on organic underlayers to modulate line-edge roughness of fine-pitch poly-silicon patterns
Authors: Miyazoe Hiroyuki , Engelmann Sebastian U. , Guillorn Michael A. , Pei Dongfei , Li Weiyi , Lauer Jason L. , Leon Shohet J. , Fuller Nicholas C. M.
Published: June 2017

Deformation of the pattern or the increase in line roughness during plasma etching becomes more significant with the shrink of complementary metal–oxide–semiconductor patterns. For aggressively scaled patternings, an organic underlayer (UL) is often used under the photoresist and a thin layer of a Si-containing hardmask. In this work, the effect of ultraviolet/vacuum ultraviolet (VUV) photons on UL parameters such as wavelength, photon dose, and process order was investigated using synchrotron radiation. First, the index of refraction and extinction coefficients of mask materials such as e-beam resist [hydrogen silsesquioxane (HSQ)] and organic UL (NFC-1400; NFC) were measured by utilizing the Kramers–Kronig relations and/or ellipsometry measurements depending on the wavelength involved. Second, VUV photons at specific wavelengths, corresponding to absorption maxima of HSQ and NFC at 54 nm (HSQ), 62 nm (HSQ and NFC), 88 nm (HSQ), 112 nm (NFC), 138 nm (HSQ), 155 nm (NFC), 194 nm (NFC), and 238 nm (NFC), were exposed before or/and after etching of NFC. The authors continued to etch into poly-Si, and the resulting line-edge roughness (LER) was measured. The improvement of the LER was seen at the wavelengths corresponding to the absorption maxima of NFC, and the degree of LER improvement was better at the higher photon dose up to 3 × 1017 photons/cm2. The LER reduced from 6.7 to 4.2 nm and to 3.6 nm when the VUV photons at wavelengths of 62 and 155 nm, respectively, were used for exposure. In contrast, pattern degradation was observed at the wavelengths corresponding to the absorption maxima of HSQ. These findings indicate that optimizing VUV radiation corresponding to the UL materials greatly influences the LER.
Chemoenzymatic Synthesis, Nanotization, and Anti-Aspergillus Activity of Optically Enriched Fluconazole Analogues
Authors: Malhotra Shashwat , Singh Seema , Rana Neha , Tomar Shilpi , Bhatnagar Priyanka , Gupta Mohit , Singh Suraj K. , Singh Brajendra K. , Chhillar Anil K. , Prasad Ashok K. , Len Christophe , Kumar Pradeep , Gupta Kailash C. , Varma Anjani J. , Kuhad Ramesh C. , Sharma Gainda L. , Parmar Virinder S. , Richards Nigel G. J.
Published: June 2017

Despite recent advances in diagnostic and therapeutic methods in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of
Candida antarctica
lipase (CAL) for the preparation of optically enriched fluconazole analogues. Anti-
Aspergillus
activity was observed for an optically enriched derivative, (−)-
S
-2-(2′,4′-difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴)triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 μg/ml and 7.8 μg/disc in broth microdilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1,000 μg/ml. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analogue exhibited improved antifungal activity against
Aspergillus fumigatus
(MIC, 1.63 μg/ml). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotized counterparts, exhibiting anti-
Aspergillus
activity may have reduced toxicity.
Potent
In Vitro
Synergism of Fluconazole and Osthole against Fluconazole-Resistant Candida albicans
Authors: Li De-Dong , Chai Dong , Huang Xiao-Wen , Guan Shao-Xing , Du Jiang , Zhang Hao-Yu , Sun Yan , Jiang Yuan-Ying
Published: June 2017

Osthole is a natural coumarin that exhibits wide biological and pharmacological activities such as neuroprotective, osteogenic, immunomodulation, antitumor, and anti-inflammatory effects. In this study, we investigated the antifungal effects of osthole
in vitro
. A checkerboard microdilution assay showed that osthole has significant synergistic effect with fluconazole against fluconazole-resistant
Candida albicans
. Similar results were obtained from a growth curve assay. Meanwhile, XTT reduction assay demonstrated the synergism of fluconazole and osthole against
C. albicans
biofilm formation. Microarray results showed that the expression of genes involved in the oxidation-reduction process, energy metabolism, and transportation changed significantly after the combined treatment with fluconazole and osthole, and further results showed that endogenous reactive oxygen species (ROS) was significantly increased in the combination group. In conclusion, these results demonstrate the synergism of fluconazole and osthole against fluconazole-resistant
C. albicans
and indicate that endogenous ROS augmentation might contribute to the synergism of fluconazole and osthole.
In Vitro-In Vivo
Discordance with Humanized Piperacillin-Tazobactam Exposures against Piperacillin-Tazobactam-Resistant/Pan-β-Lactam-Susceptible Klebsiella pneumoniae Strains
Authors: Stainton S. M. , Monogue M. L. , Nicolau D. P.
Published: June 2017

Recent findings have identified
Klebsiella pneumoniae
strains that are pan-β-lactam susceptible (PBL-S) but piperacillin-tazobactam resistant (TZP-R)
in vitro
. We assessed the efficacy of a humanized exposure of piperacillin-tazobactam (TZP) against 12 TZP-R/PBL-S
K. pneumoniae
isolates in an immunocompromised murine lung infection model. Discordance between the
in vitro
resistance profile and the
in vivo
efficacy of human-simulated TZP exposures against this phenotypic profile was observed. Additional studies are required to define the clinical implications of these TZP-R/PBL-S strains.
Comparison of Two Phenotypic Algorithms To Detect Carbapenemase-Producing Enterobacteriaceae
Authors: Dortet Laurent , Bernabeu Sandrine , Gonzalez Camille , Naas Thierry
Published: June 2017

A novel algorithm designed for the screening of carbapenemase-producing
Enterobacteriaceae
(CPE), based on faropenem and temocillin disks, was compared to that of the Committee of the Antibiogram of the French Society of Microbiology (CA-SFM), which is based on ticarcillin-clavulanate, imipenem, and temocillin disks. The two algorithms presented comparable negative predictive values (98.6% versus 97.5%) for CPE screening among carbapenem-nonsusceptible
Enterobacteriaceae
. However, since 46.2% (
n
= 49) of the CPE were correctly identified as OXA-48-like producers by the faropenem/temocillin-based algorithm, it significantly decreased the number of complementary tests needed (42.2% versus 62.6% with the CA-SFM algorithm).
Retrospective Cohort Analysis of Liposomal Amphotericin B Nephrotoxicity in Patients with Hematological Malignancies
Authors: Stanzani Marta , Vianelli Nicola , Cavo Michele , Maritati Alessandro , Morotti Marta , Lewis Russell E.
Published: June 2017

We retrospectively examined the incidence, onset, risk factors, and outcomes of renal injury during 103 treatment courses of liposomal amphotericin B (L-AMB) in 97 adult patients with hematological malignancies. All the patients were analyzed before, during, and after the administration of L-AMB, and renal injury was graded according to the RIFLE criteria (risk, injury, failure, loss of function, end-stage renal disease). Most patients (87.3%) received L-AMB at 3 mg/kg of body weight/day. Nearly two-thirds (61.7%) of the treatment courses did not meet any RIFLE category for renal injury, while 19.4% of patients were classified at risk, 13.6% met an injury classification, and 5.8% were categorized as developing renal failure. However, 15% of the patients developed renal injury within 48 h of the onset of multiorgan failure associated with sepsis, bleeding, or progressing malignancy. When these patients were analyzed as a competing risk for L-AMB-associated renal injury (RIFLE category I or above) in a multivariate Cox regression model, receipt of cyclosporine (subhazard ratio [SHR], 2.62; 95% confidence interval [CI], 1.10 to 6.27;
P
= 0.03), cyclosporine plus furosemide at ≥40 mg/day (SHR, 5.46; 95% CI, 1.89 to 15.74;
P
= 0.002), or cyclosporine plus foscarnet (SHR, 9.03; 95% CI, 3.68 to 22.14;
P
< 0.0001) were the only comedications significantly associated with increased rates of renal injury. The cumulative incidence of L-AMB renal injury during the first 10 days of therapy was 7% overall but only 3% in patients who were not receiving cyclosporine. Hence, the renal risk of L-AMB therapy may be lessened if patients are switched to alternative agents after 7 to 10 days or if aggressive diuresis and/or foscarnet is avoided, especially among patients receiving calcineurin inhibitors.
Toothpick-induced aortoenteric fistula presenting as sepsis
Authors: Liao Elizabeth , Simons Martin , Tse Leonard W , Roche-Nagle Graham
Published: June 2017

Aortoenteric fistulas (AEF) are a rare but life-threatening cause of gastrointestinal (GI) bleeding. We present the case of a primary AEF caused by ingestion of a toothpick by a 47-year-old male. This is the 10th known case in the literature in which a foreign body was found to be the cause of a communication between the aorta and the GI tract. Most foreign objects have been sewing needles; this is the first known case of a toothpick penetration. The patient presented to our institution with polymicrobial sepsis and bilateral pulmonary septic emboli. The patient was successfully treated but required multiple interventions and a prolonged intensive care unit admission.
Prevalence, clinical features and risk assessment of pre-diabetes in Spain: the prospective Mollerussa cohort study
Authors: Vilanova María Belén , Falguera Mireia , Marsal Josep Ramon , Rubinat Esther , Alcubierre Núria , Catelblanco Esmeralda , Granado-Casas Minerva , Miró Neus , Molló Àngels , Mata-Cases Manel , Franch-Nadal Josep , Mauricio Didac
Published: June 2017

Purpose

The Mollerussa prospective cohort was created to study pre-diabetes in a population-based sample from the primary care setting in the semirural area of Pla d’Urgell in Catalonia (Spain). The aims of the study were to assess the prevalence of pre-diabetes in our population, the likelihood to develop overt diabetes over time and to identify risk factors associated with the progression of the condition.

Participants

The cohort includes 594 subjects randomly selected between March 2011 and July 2014 from our primary care population, who were older than 25 years, consented to participate and did not have a recorded diagnosis of diabetes.

Findings to date

At baseline, we performed a clinical interview to collect demographic, clinical and lifestyle (including a nutritional survey) characteristics; carotid ultrasound imaging to assess subclinical cardiovascular disease was also performed, and a blood sample was collected, with an overall <5% rate of missing data. An additional blood draw was performed 12 months after initial recruitment to reassess laboratory results in patients initially identified as having pre-diabetes, with an 89.6% retention rate. Several studies investigating various hypotheses are currently ongoing.

Future plans

All subjects recruited during the cohort creation will be followed long-term through annual extraction of data from health records stored in the electronic Clinical station in Primary Care database. The Mollerussa cohort will thus be a sound population-based sample for multiple future research projects to generate insights into the epidemiology and natural history of pre-diabetes in Spain.
Estimating the incidence and the economic burden of third and fourth-degree obstetric tears in the English NHS: an observational study using propensity score matching
Authors: Orlovic Martina , Carter Alexander William , Marti Joachim , Mossialos Elias
Published: June 2017

Objective

Obstetric care is a high-risk area in healthcare delivery, so it is essential to have up-to-date quantitative evidence in this area to inform policy decisions regarding these services. In light of this, the objective of this study is to investigate the incidence and economic burden of third and fourth-degree lacerations in the English National Health Service (NHS) using recent national data.

Methods

We used coded inpatient data from Hospital Episode Statistics (HES) for the financial years from 2010/2011 to 2013/2014 for all females that gave birth during that period in the English NHS. Using HES, we used pre-existing safety indicator algorithms to calculate the incidence of third and fourth-degree obstetric tears and employed a propensity score matching method to estimate the excess length of stay and economic burden associated with these events.

Results

Observed rates per 1000 inpatient episodes in 2010/2011 and 2013/2014, respectively: Patient Safety Indicator—trauma during vaginal delivery with instrument (PSI 18)=84.16 and 91.24; trauma during vaginal delivery without instrument (PSI 19)=29.78 and 33.43; trauma during caesarean delivery (PSI 20)=3.61 and 4.56. Estimated overall (all PSIs) economic burden for 2010/2011=£10.7 million and for 2013/2014=£14.5 million, expressed in 2013/2014 prices.

Conclusions

Despite many initiatives targeting the quality of maternity care in the NHS, the incidence of third and fourth-degree lacerations has increased during the observed period which signals that quality improvement efforts in obstetric care may not be reducing incidence rates. Our conservative estimates of the financial burden of these events appear low relative to total NHS expenditure for these years.
What impact has the NIHR Academic Clinical Fellowship (ACF) scheme had on clinical academic careers in England over the last 10 years? A retrospective study
Authors: Clough Sally , Fenton James , Harris-Joseph Helen , Rayton Leesa , Magee Caroline , Jones David , Cotterill Lisa Ann , Neilson James
Published: June 2017

Objectives

The Academic Clinical Fellowship (ACF) was introduced to support the early career clinical and research training of potential future clinical academics in England. The driver for the model was concern about falling numbers of clinical academic trainees. This study examines the impact of the ACF model, over its first 10 years, in developing clinical academic careers by tracking the progression of ACF trainees.

Design

Retrospective analysis of National Institute for Health Research (NIHR) ACF career progression. This was performed using mixed methods including routine data collections of career destination, analysis of application rates to doctoral level fellowships and supplemented by survey information that captured the perceived benefits and challenges from previous ACFs and their current career activities.

Participants

1239 NIHR ACFs who completed or left their posts between 2006 and March 2015.

Results

ACFs are perceived by the candidate population as attractive posts, with high numbers of applications leading to high fill rates. Balancing clinical and academic commitments is one of the reported challenges when completing an ACF. We have found that undertaking an ACF was shown to increase the likelihood of securing an externally funded doctoral training award and the vast majority of ACFs move into academic roles, with many completing PhDs. Previous ACFs continue to show positive career progression, predominantly in translational and clinical research. The knowledge acquired during the ACF continues to be useful in subsequent roles and trainees would recommend the scheme to others.

Conclusions

The NIHR ACF scheme is successful as part of an integrated training pathway in developing careers in academic medicine and dentistry.
Knowledge, facilitators and barriers to cervical cancer screening among women in Uganda: a qualitative study
Authors: Ndejjo Rawlance , Mukama Trasias , Kiguli Juliet , Musoke David
Published: June 2017

Objectives

To explore community knowledge, facilitators and barriers to cervical cancer screening among women in rural Uganda so as to generate data to inform interventions.

Design

A qualitative study using focus group discussions and key informant interviews.

Setting

Discussions and interviews carried out in the community within two districts in Eastern Uganda.

Participants

Ten(10) focus group discussions with 119 screening-eligible women aged between 25 and 49 years and 11 key informant interviews with healthcare providers and administrators.

Results

Study participants’ knowledge about cervical cancer causes, signs and symptoms, testing methods and prevention was poor. Many participants attributed the cause of cervical cancer to use of contraception while key informants said that some believed it was due to witchcraft. Perceptions towards cervical cancer and screening were majorly positive with many participants stating that they were at risk of getting cervical cancer. The facilitators to accessing cervical cancer screening were: experiencing signs and symptoms of cervical cancer, family history of the disease and awareness of the disease/screening service. Lack of knowledge about cervical cancer and screening, health system challenges, fear of test outcome and consequences and financial constraints were barriers to cervical cancer screening.

Conclusion

Whereas perceptions towards cervical cancer and screening were positive, knowledge of study participants on cervical cancer was poor. To improve cervical cancer screening, effort should be focused on reducing identified barriers and enhancing facilitators.
Integrated care for resected early stage lung cancer: innovations and exploring patient needs
Authors: Ho Jan , McWilliams Annette , Emery Jon , Saunders Christobel , Reid Christopher , Robinson Suzanne , Brims Fraser
Published: June 2017

There is no consensus as to the duration and nature of follow-up following surgical resection with curative intent of lung cancer. The integration of cancer follow-up into primary care is likely to be a key future area for quality and cost-effective cancer care. Evidence from other solid cancer types demonstrates that such follow-up has no adverse outcomes, similar health-related quality of life, high patient satisfaction rates at a lower cost to the healthcare system. Core elements for successful models of shared cancer care are required: clear roles and responsibilities, timely effective communication, guidance on follow-up protocols and common treatments and rapid routes to (re)access specialist care. There is thus a need for improved communication between hospital specialists and primary care. Unmet needs for patients with early stage lung cancer are likely to include psychological symptoms and carer stress; the importance of smoking cessation may frequently be overlooked or underappreciated in the current hospital-based follow-up system. There is therefore a need for quality randomised controlled trials of patients with resected early stage lung cancer to establish optimal protocols for primary care-based follow-up and to more adequately address patients' and carers' unmet psychosocial needs, including the crucial role of smoking cessation.