bluuebunny/crossref_metadata_2025 huggingface dataset:
Unintentional Pharmaceutical‐Related Medication Errors Caused by Laypersons Reported to the Toxicological Information Centre in the Czech Republic
Authors: Urban Michal , Leššo Roman , Pelclová Daniela
Published: March 2016

The purpose of the article was to study unintentional pharmaceutical‐related poisonings committed by laypersons that were reported to the Toxicological Information Centre in the Czech Republic. Identifying frequency, sources, reasons and consequences of the medication errors in laypersons could help to reduce the overall rate of medication errors. Records of medication error enquiries from 2013 to 2014 were extracted from the electronic database, and the following variables were reviewed: drug class, dosage form, dose, age of the subject, cause of the error, time interval from ingestion to the call, symptoms, prognosis at the time of the call and first aid recommended. Of the calls, 1354 met the inclusion criteria. Among them, central nervous system‐affecting drugs (23.6%), respiratory drugs (18.5%) and alimentary drugs (16.2%) were the most common drug classes involved in the medication errors. The highest proportion of the patients was in the youngest age subgroup 0–5 year‐old (46%). The reasons for the medication errors involved the leaflet misinterpretation and mistaken dose (53.6%), mixing up medications (19.2%), attempting to reduce pain with repeated doses (6.4%), erroneous routes of administration (2.2%), psychiatric/elderly patients (2.7%), others (9.0%) or unknown (6.9%). A high proportion of children among the patients may be due to the fact that children's dosages for many drugs vary by their weight, and more medications come in a variety of concentrations. Most overdoses could be prevented by safer labelling, proper cap closure systems for liquid products and medication reconciliation by both physicians and pharmacists.
Integrating socio‐cultural contexts and location‐based systems for ubiquitous language learning in museums: A state of the art review of 2009–2014
Authors: Wang Hong‐You , Liu Gi‐Zen , Hwang Gwo‐Jen
Published: March 2016

Context‐dependent learning systems are now becoming more common in museums, as most students are equipped with mobile devices. As there has been little research into context‐aware mobile applications in museums, the present study aims to investigate ubiquitous language learning in socio‐cultural contexts, as well as recent trends in using location‐based systems. Therefore, the following three issues are reviewed in related articles published between 2009 and 2014: system usefulness, activity usefulness and activity playfulness in museum learning. The researchers used keywords to search for relevant articles from the ISI (Institute for Scientific Information) Web of Science and other databases. The abstracts and content of the searched articles were then analyzed. The results show that the location‐aware features (GPS or Google App‐based) embedded in mobile phones, adaptive language learning and socio‐cultural interaction in museums are intertwined in the literature. The literature also shows that in recent years students have transformed from being passive receivers to active learners. Specifically, students tended to rely on system guidance in 2009–2011, and activities were more focused on individual learning with less real‐life social interaction, and this thus reduced the level of playfulness. An important finding in the literature from 2012 to 14 is that many museums adopted ubiquitous location‐based systems using mobile devices, which help to strengthen social ties when students work collaboratively to perform language learning activities. This has also allowed museums to evolve from mobile‐learning to ubiquitous‐learning environments, in various socio‐cultural contexts. The results of this review study have implications for language teachers and museum educators, to help them implement appropriate ubiquitous learning systems in various socio‐cultural contexts.
Introducing electronic textbooks as daily‐use technology in schools: A top‐down adoption process
Authors: Chiu Thomas K. F.
Published: March 2016

This study took frequency of use and the adoption process into account to define the participants and external variables of the research model. School electronic textbooks are a daily‐use technology and they are adopted in a compulsory, top‐down way. Their introduction can evoke feelings of anxiety among teachers because of a possible increase in workload. This compulsory adoption process contrasts with that for most other technologies, which are voluntary and less disruptive. In a school context, instructional designs of electronic textbooks that help explain user acceptance are sufficient in a bottom‐up, but not a top‐down, approach. To address this, individual, organizational, and social factors were included in our research model. A survey questionnaire to collect data from 306 in‐service teachers from eight secondary schools was used. The results showed that anxiety and positive attitude were the main barrier and catalyst, respectively, to the acceptance of such technology. One suggestion for researchers and two suggestions for school leaders on the adoption process were made.
Interaction pattern analysis in cMOOCs based on the connectivist interaction and engagement framework
Authors: Wang Zhijun , Anderson Terry , Chen Li , Barbera Elena
Published: March 2016

Connectivist learning is interaction‐centered learning. A framework describing interaction and cognitive engagement in connectivist learning was constructed using logical reasoning techniques. The framework and analysis was designed to help researchers and learning designers understand and adapt the characteristics and principles of interaction in connectivist learning contexts. In this study empirical evidence to support and further develop this framework is presented. This study analyzed 6 weeks of data harvested from the daily newsletter, Twitter, and a Facebook group in a well‐known cMOOC led by George Siemens and Stephen Downes. These text transcripts were analyzed using a deductive approach of qualitative content analysis. This study revealed the main activity patterns of participants as they engage in four levels of interaction (operation interaction, wayfinding interaction, sensemaking interaction, and innovation interaction) during the MOOC. Generally the framework serves as a conceptual model to understand and to analyze the interaction in this cMOOC, although some implied interaction is hard to recognize and categorize. The relationship of the four levels of interaction and the role of each element in the framework were explored with the intent of offering the framework as a conceptual and analytic tool to guide both researchers and practitioners in designing and studying connectivist learning.
Design possibilities for the e‐Schoolbag: Addressing the 1:1 challenge within China
Authors: Gu Xiaoqing , Xu Xiaojuan , Wang Huawen , Crook Charles
Published: March 2016

There is widespread enthusiasm for 1:1 computing in education. Recognizing that secure innovation of educational practice should be built upon contextual sensitivity, this article reported two case studies anticipating the potential development of 1:1 classes in the particular cultural context of China. The first case described how the new technology of e‐Textbooks could align with a tradition where the textbook is central to teaching practice. A science teacher used the e‐Textbook to design his pedagogy to accommodate the contextual learning needs of the classroom. Students reported a positive reaction. They understood that new learning possibilities were crafted through this engagement with diversified media formats that content fitted their class, and this gave them increased confidence in relation to both student–computer and interpersonal interaction. The second case study described how a social app could align with the local tradition of practice whereby a student's performance in front of class is an important part of instructional practice. In this case, students who were learning native Chinese were offered the opportunity for performing within a novel “digital stage”: revealing high levels of engagement and a strengthening confidence with language performance.
The effect of the flipped classroom approach to OpenCourseWare instruction on students’ self‐regulation
Authors: Sun Jerry Chih‐Yuan , Wu Yu‐Ting , Lee Wei‐I
Published: March 2016

The purpose of this study was to investigate the effect of the flipped classroom approach to OpenCourseWare instruction on students’ self‐regulation. OpenCourseWare was integrated into the flipped classroom model (experimental group) and distance learning (control group). Overall, 181 freshmen taking a physics course were allowed to choose their own class based on their preferred teaching method (experimental or control group). The findings indicated that there was no significant between‐group difference in terms of self‐regulation. However, when comparing the means for the six categories of self‐regulation, the results showed that the experimental group learners had significantly higher scores for the category of help‐seeking. The use of the flipped classroom model created a learning environment which prompted its learners to proactively seek external help. These learners were more aware of their need for external help in their studies and were able to identify the person/people who could solve their academic problems, while they were able to find the appropriate means to do so and actually obtain help. The results of this study can serve as a reference for future studies on the flipped classroom model and OpenCourseWare, as well as for teachers and researchers in related fields.
Single versus tandem high‐dose melphalan followed by autologous blood stem cell transplantation in multiple myeloma: long‐term results from the phase III GMMG‐HD2 trial
Authors: Mai Elias K. , Benner Axel , Bertsch Uta , Brossart Peter , Hänel Annette , Kunzmann Volker , Naumann Ralph , Neben Kai , Egerer Gerlinde , Ho Anthony D. , Hillengass Jens , Raab Marc S. , Neubauer Andreas , Peyn Astrid , Ko Yon‐Dschun , Peter Norma , Scheid Christof , Goldschmidt Hartmut
Published: March 2016

The prospective, randomized phase III trial GMMG‐HD2 aimed at demonstrating non‐inferiority of single (Arm A) versus tandem (Arm B) high‐dose melphalan followed by autologous transplantation (HDM/ASCT) with regard to 2‐year event‐free survival (EFS) in newly‐diagnosed multiple myeloma (MM) and included 358 evaluable patients [Intention‐to‐treat population, (ITT), single/tandem HDM/ASCT: n = 177/181].

After a median follow‐up of more than 11 years, non‐inferiority of single versus tandem HDM/ASCT was demonstrated using the planned non‐inferiority threshold of 15% of the 2‐year EFS rate. Neither EFS (P = 0·53) nor overall survival (OS) (P = 0·33) differences were observed in the ITT population. In the tandem arm, 26% (n = 47/181) of patients refused a second HDM/ASCT due to non‐medical reasons. A per‐protocol (PP) analysis, including patients who received the intervention (single/tandem HDM/ASCT: n = 156/93) and patients who did not receive a second HDM/ASCT due to medical reasons (12%, n = 22/181), did not yield differences in EFS (P = 0·61) or OS (P = 0·16). In the ITT and PP set of the tandem arm, the rates of complete responses increased from first to second HDM/ASCT (both P = 0·04). Ten‐year OS for the entire ITT was 34% (95% confidence interval: 29–40%). OS after first relapse was significantly shortened in the tandem arm (P = 0·04). In this study single HDM/ASCT was non‐inferior to tandem HDM/ASCT in MM.
Current status and future directions of T‐lymphoblastic lymphoma in children and adolescents
Authors: Burkhardt Birgit , Mueller Stephanie , Khanam Tasneem , Perkins Sherrie L.
Published: March 2016

The main challenges in the treatment of T‐cell lymphoblastic lymphoma (T‐LBL) in children and adolescents are twofold: to increase survival rates in concert with reduction of acute and long‐term toxicities including the rate of secondary malignancies. The need for molecular and prognostic markers in T‐LBL is crucial to allow for systematic treatment optimization and may serve as targets for new treatment approaches.
Mature T‐ and NK‐cell non‐Hodgkin lymphoma in children and young adolescents
Authors: Pillai Vinodh , Tallarico Michael , Bishop Michael R. , Lim Megan S.
Published: March 2016

Mature T/Natural killer (NK)‐cell neoplasms of children and the young adolescent population exhibit higher prevalence in Central and South American and Asian populations and many are associated with Epstein‐Barr virus (EBV). They are represented in large part by extranodal T/NK cell lymphomas‐ nasal‐type or extra nasal‐type, chronic lymphoproliferative disorders of T/NK cells or chronic active EBV disease, systemic EBV‐positive lymphoproliferative disorders of childhood, hydroa vacciniforme‐like lymphoma, hepatosplenic T‐cell lymphoma and primary cutaneous gamma/delta T‐cell lymphoma among others. Many T/NK cell neoplasms in this age group are derived from cells of the innate immune system, in contrast to adults where they are predominantly from the adaptive immune system. The genetic basis of T/NK cell lymphomas in children and young adolescents remains largely unknown. Anthracycline‐based regimens and haematopoietic stem cell transplants (allogeneic and autologous) are current treatment modalities, however it is anticipated that novel targeted therapeutic agents will be available in the near future.
Investigating peer attitudes towards the use of key word signing by children with Down syndrome in mainstream schools
Authors: Bowles Caoimhe , Frizelle Pauline
Published: March 2016

Accessible Summary

This research looked at young children's attitudes towards the use of a signing system by children with Down syndrome, in mainstream school.

These attitudes can help to reveal factors which support the successful use of signing as well as those that make it difficult to use signs effectively in a mainstream setting.

The results show that although children expressed a number of difficulties in relation to signing, overall they have a positive attitude towards signing on which we should capitalise, to enhance the communicative experiences of both the children with Down syndrome and their peers in mainstream school.

Background: Lámh is a key word signing approach used in Ireland, which can support the communication needs of children with Down syndrome. However, the success of this approach in mainstream schools relies heavily on the attitudes of those within the school environment. To date, two studies have explored the attitudes of teaching staff towards the use of keyword signing in schools; however, no previous research has investigated peer attitudes towards this method of communication. This study aimed to explore the attitudes of peers towards the use of Lámh by children with Down syndrome in mainstream schools.

Materials and Methods: The study was qualitative, using interpretative phenomenological analysis procedures to analyse eight interviews with children, ranging in age from 6 to 8 years.

Results and Conclusion: Overall, mainstream school peers demonstrated an understanding and an appreciation of the use of key word signing. However, the success of this approach within the school was limited by a number of challenges evinced by the school peers, including making the signs accurately and remembering their meanings. Given the important interactive role of the peers of a child with Down syndrome in a mainstream school setting, these challenges need to be addressed to optimise the use of key word signing and increase the likelihood of successful communication between children with Down syndrome and their peers.
New insights into the yin and yang of the endocannabinoid system in health and disease
Authors: Wainwright Cherry L
Published: March 2016

Linked Articles

This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.
Effects of glucagon‐like peptide‐1 on the differentiation and metabolism of human adipocytes
Authors: El Bekay Rajaa , Coín‐Aragüez Leticia , Fernández‐García Diego , Oliva‐Olivera Wilfredo , Bernal‐López Rosa , Clemente‐Postigo Mercedes , Delgado‐Lista Javier , Diaz‐Ruiz Alberto , Guzman‐Ruiz Rocío , Vázquez‐Martínez Rafael , Lhamyani Said , Roca‐Rodríguez María Mar , Veledo Sonia Fernandez , Vendrell Joan , Malagón María M. , Tinahones Francisco José
Published: March 2016

Background and Purpose

Glucagon‐like peptide‐1 (GLP‐1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss in obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP‐1 receptor, which is present in adipocytes and the stromal vascular fraction of human adipose tissue (AT), is up‐regulated in AT of insulin‐resistant morbidly obese subjects compared with healthy lean subjects. The aim of this study was to explore the effects of in vitro and in vivo administration of GLP‐1 and its analogues on AT and adipocyte functions from T2D morbidly obese subjects.

Experimental Approach

We analysed the effects of GLP‐1 on human AT and isolated adipocytes in vitro and the effects of GLP‐1 mimetics on AT of morbidly obese T2D subjects in vivo.

Key Results

GLP‐1 down‐regulated the expression of lipogenic genes when administered during in vitro differentiation of human adipocytes from morbidly obese patients. GLP‐1 also decreased the expression of adipogenic/lipogenic genes in AT explants and mature adipocytes, while increasing that of lipolytic markers and adiponectin. In 3T3‐L1 adipocytes, GLP‐1 decreased free cytosolic Ca2+ concentration ([Ca2+]i). GLP‐1‐induced responses were only partially blocked by GLP‐1 receptor antagonist exendin (9–39). Moreover, administration of exenatide or liraglutide reduced adipogenic and inflammatory marker mRNA in AT of T2D obese subjects.

Conclusions and Implications

Our data suggest that the beneficial effects of GLP‐1 are associated with changes in the adipogenic potential and ability of AT to expand, via activation of the canonical GLP‐1 receptor and an additional, as yet unknown, receptor.
Genetic abnormalities associated with acute lymphoblastic leukemia
Authors: Yokota Takafumi , Kanakura Yuzuru
Published: March 2016

Acute lymphoblastic leukemia (ALL) occurs with high frequency in childhood and is associated with high mortality in adults. Recent technical advances in next‐generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to ALL pathogenesis. Based on these genetic abnormalities, ALL is now being reclassified into newly identified subtypes. Philadelphia chromosome‐like B‐lineage ALL is one of the new high‐risk subtypes characterized by genetic alterations that activate various signaling pathways, including those involving cytokine receptors, tyrosine kinases, and epigenetic modifiers. Philadelphia chromosome‐like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses. Whole‐genome sequencing studies of ALL patients and ethnically matched controls also identified inherited genetic variations in lymphoid neoplasm‐related genes, which are likely to increase ALL susceptibility. These findings are directly relevant to clinical hematology, and further studies on this aspect could contribute to accurate diagnosis, effective monitoring of residual disease, and patient‐oriented therapies.
Insights into Medium‐chain Acyl‐CoA Dehydrogenase Structure by Molecular Dynamics Simulations
Authors: Bonito Cátia A. , Leandro Paula , Ventura Fátima V. , Guedes Rita C.
Published: March 2016

The medium‐chain acyl‐CoA dehydrogenase (MCAD) is a mitochondrial enzyme that catalyzes the first step of mitochondrial fatty acid β‐oxidation (mFAO) pathway. Its deficiency is the most common genetic disorder of mFAO. Many of the MCAD disease‐causing variants, including the most common p.K304E variant, show loss of function due to protein misfolding. Herein, we used molecular dynamics simulations to provide insights into the structural stability and dynamic behavior of MCAD wild‐type (MCADwt) and validate a structure that would allow reliable new studies on its variants. Our results revealed that in both proteins the flavin adenine dinucleotide (FAD) has an important structural role on the tetramer stability and also in maintaining the volume of the enzyme catalytic pockets. We confirmed that the presence of substrate changes the dynamics of the catalytic pockets and increases FAD affinity. A comparison between the porcine MCADwt (pMCADwt) and human MCADwt (hMCADwt) structures revealed that both proteins are essentially similar and that the reversion of the double mutant E376G/T255E of hMCAD enzyme does not affect the structure of the protein neither its behavior in simulation. Our validated hMCADwt structure is crucial for complementing and accelerating the experimental studies aiming for the discovery and development of potential stabilizers of MCAD variants as candidates for the treatment of MCAD deficiency (MCADD).
Young Children Understand the Role of Agreement in Establishing Arbitrary Norms—But Unanimity Is Key
Authors: Schmidt Marco F. H. , Rakoczy Hannes , Mietzsch Teresa , Tomasello Michael
Published: March 2016

Human cultural groups value conformity to arbitrary norms (e.g., rituals, games) that are the result of collective “agreement.” Ninety‐six 3‐year‐olds had the opportunity to agree upon arbitrary norms with puppets. Results revealed that children normatively enforced these novel norms only on a deviator who had actually entered into the agreement (not on dissenting or ignorant individuals). Interestingly, any dissent during the norm‐setting process (even if a majority of 90% preferred one course of action) prevented children from seeing a norm as established for anyone at all. These findings suggest that even young children understand something of the role of agreement in establishing mutually binding social norms, but that their notion of norm formation may be confined to conditions of unanimity.
Sputum interleukin‐13 as a biomarker for the evaluation of asthma control
Authors: Tsilogianni Z. , Hillas G. , Bakakos P. , Aggelakis L. , Konstantellou E. , Papaioannou A. I. , Papaporfyriou A. , Papiris S. , Koulouris N. , Loukides S. , Kostikas K.
Published: March 2016

Background

Asthma control refers to the extent to which the manifestations of asthma have been reduced or eradicated by treatment. Interleukin‐13 (IL‐13) has a central role in Th2 response and serves as a possible therapeutic target in uncontrolled asthma. Fraction of exhaled nitric oxide (FeNO) and sputum eosinophils have modest performance in the evaluation of asthma control.

Objective

To assess the diagnostic performance of sputum IL‐13 for the evaluation of asthma control and furthermore to investigate the performance of sputum eosinophils and FeNO.

Methods

One hundred and seventy patients with asthma were studied. All subjects underwent assessment of asthma control by asthma control test (ACT), lung function tests, FeNO measurement and sputum induction for cell count identification and IL‐13 measurement in supernatants.

Results

IL‐13 (pg/mL) levels in sputum supernatant differed significantly among patients with well‐controlled asthma and those with not well‐controlled asthma [median IQR 78 (66–102) vs. 213 (180–265), P < 0.001]. Receiver operating characteristic (ROC) analysis showed that, for the whole study population, the diagnostic performance of IL‐13 was superior to both sputum eosinophils and FeNO levels [area under the curve (AUC) 0.92, 95% CI 0.87 to 0.95 vs. AUC 0.65, 95% CI 0.58 to 0.72 vs. AUC 0.65, 95% CI 0.55 to 0.72, respectively].

Conclusion

The diagnostic performance of sputum IL‐13 was superior to both sputum eosinophils and FeNO levels for the identification of well‐controlled asthma. Sputum IL‐13 levels could serve as a useful biomarker for asthma control assessment.
The differential effects of 1,25-dihydroxyvitamin D3 on Salmonella-induced interleukin-8 and human beta-defensin-2 in intestinal epithelial cells
Authors: Huang F-C
Published: March 2016

Salmonellosis or Salmonella, one of the most common food-borne diseases, remains a major public health problem worldwide. Intestinal epithelial cells (IECs) play an essential role in the mucosal innate immunity of the host to defend against the invasion of Salmonella by interleukin (IL)−8 and human β-defensin-2 (hBD-2). Accumulated research has unravelled important roles of vitamin D in the regulation of innate immunity. Therefore, we investigated the effects of 1,25-dihydroxyvitamin D3 (1,25D3) on Salmonella-induced innate immunity in IECs. We demonstrate that pretreatment of 1,25D3 results in suppression of Salmonella-induced IL-8 but enhancement of hBD-2, either protein secretion and mRNA expression, in IECs. Furthermore, 1,25D3 enhanced Salmonella-induced membranous recruitment of nucleotide oligomerization domain (NOD2) and its mRNA expression and activation of protein kinase B (Akt), a downstream effector of phosphoinositide 3-kinase (PI3K). Inhibition of the PI3K/Akt signal counteracted the suppressive effect of 1,25D3 on Salmonella-induced IL-8 expression, while knock-down of NOD2 by siRNA diminished the enhanced hBD-2 expression. These data suggest differential regulation of 1,25D3 on Salmonella-induced IL-8 and hBD-2 expression in IECs via PI3K/Akt signal and NOD2 protein expression, respectively. Active vitamin D-enhanced anti-microbial peptide in Salmonella-infected IECs protected the host against infection, while modulation of proinflammatory responses by active vitamin D prevented the host from the detrimental effects of overwhelming inflammation. Thus, active vitamin D-induced innate immunity in IECs enhances the host's protective mechanism, which may provide an alternative therapy for invasive Salmonella infection.
Granulocyte colony-stimulating factor impairs CD8+ T cell functionality by interfering with central activation elements
Authors: Bunse C E , Tischer S , Lahrberg J , Oelke M , Figueiredo C , Blasczyk R , Eiz-Vesper B
Published: March 2016

Besides mobilizing stem cells into the periphery, granulocyte colony-stimulating factor (G-CSF) has been shown to influence various types of innate and adaptive immune cells. For example, it impairs the effector function of cytotoxic T lymphocytes (CTLs). It is assumed that this effect is mediated indirectly by monocytes, regulatory T cells and immunomodulatory cytokines influenced by G-CSF. In this study, isolated G-CSF-treated CD8+ T cells were stimulated antigen-dependently with peptide–major histocompatibility complex (pMHC)-coupled artificial antigen-presenting cells (aAPCs) or stimulated antigen-independently with anti-CD3/CD28 stimulator beads. By measuring the changes in interferon (IFN)-γ and granzyme B expression at the mRNA and protein level, we showed for the first time that G-CSF has a direct effect on CD8+ CTLs, which was confirmed based on the reduced production of IFN-γ and granzyme B by the cytotoxic T cell line TALL-104 after G-CSF treatment. By investigating further elements affected by G-CSF in CTLs from stem cell donors and untreated controls, we found a decreased phosphorylation of extracellular-regulated kinase (ERK)1/2, lymphocyte-specific protein tyrosine kinase (Lck) and CD3ζ after G-CSF treatment. Additionally, miRNA-155 and activation marker expression levels were reduced. In summary, our results show that G-CSF directly influences the effector function of cytotoxic CD8+ T cells and affects various elements of T cell activation.
Effect of supine body position on central corneal thickness
Authors: Maslin Jessica S , Teng Christopher C , Chadha Nisha , Liu Ji
Published: March 2016

Background

To evaluate the effect of supine body position on central corneal thickness (CCT) in open‐angle glaucoma patients and in healthy subjects.

Design

A cross‐sectional study at a university eye clinic.

Participants

Twenty‐three subjects were recruited in each group, for a total of 46 patients.

Methods

CCT was measured using an ultrasound pachymeter in each subject. Three consecutive measurements in each eye were first taken in the sitting position, and repeated after 10 min and 30 min in a supine position. Results were analyzed using mixed model repeated measures, which adjusted for age, gender and laterality of eyes.

Main Outcome Measures

CCT

Results

In healthy subjects, CCT decreased with supine positioning at 10 min (mean = −5.2 µm, P = 0.0043) and at 30 min (mean = −6.5 µm, P < 0.0001). In the glaucoma group, CCT decreased with supine positioning at 10 min (mean = −6.7 µm, P = 0.0043) and at 30 min (mean = −10.2 µm, P < 0.0001). There was no statistically significant difference between the CCT at 10 min supine and at 30 min supine in the healthy subjects (P = 0.37) and glaucoma patients (P = 0.14). CCT was shown to decrease linearly over time (P < 0.0001), and the slopes were not statistically different between groups (P = 0.40).

Conclusions

CCT is a dynamic measurement that can be influenced by body position. It decreases linearly in the first 30 min of supine positioning at a similar rate in both open angle glaucoma patients and in healthy subjects.
Non‐ionizing real‐time ultrasonography in implant and oral surgery: A feasibility study
Authors: Chan Hsun‐Liang , Wang Hom‐Lay , Fowlkes Jeffery Brian , Giannobile William V. , Kripfgans Oliver D.
Published: March 2016

Purpose

Ultrasound imaging has potential to complement radiographic imaging modalities in implant and oral surgery given that it is non‐ionizing and provides instantaneous images of anatomical structures. For application in oral and dental imaging, its qualities are dependent on its ability to accurately capture these complex structures. Therefore, the aim of this feasibility study was to investigate ultrasound to image soft tissue, hard tissue surface topography and specific vital structures.

Material and methods

A clinical ultrasound scanner, paired with two 14‐MHz transducers of different sizes (one for extraoral and the other for intraoral scans), was used to scan the following structures on a fresh cadaver: (i) the facial bone surface and soft tissue of maxillary anterior teeth, (ii) the greater palatine foramen; (iii) the mental foramen and (iv) the lingual nerve. Multiple measurements relevant to these structures were made on the ultrasound images and compared to those on cone‐beam computed tomography (CBCT) scans and/or direct measurements.

Results

Ultrasound imaging could delineate hard tissue surfaces, including enamel, root dentin and bone as well as soft tissue with high resolution (110 μm wavelength). The greater palatine foramen, mental foramen and lingual nerve were clearly shown in ultrasound images. Merging ultrasound and CBCT images demonstrated overall spatial accuracy of ultrasound images, which was corroborated by data gathered from direct measurements.

Conclusion

For the first time, this study provides proof‐of‐concept evidence that ultrasound can be a real‐time and non‐invasive alternative for the evaluation of oral and dental anatomical structures relevant for implant and oral surgery.
Determinants of biofilm formation and cleanability of titanium surfaces
Authors: Zaugg Lucia K. , Astasov‐Frauenhoffer Monika , Braissant Olivier , Hauser‐Gerspach Irmgard , Waltimo Tuomas , Zitzmann Nicola U.
Published: March 2016

Objective

The aim of the present study was to analyze biofilm formation on four different titanium‐based surfaces (machined titanium zirconium (TiZr) alloy, M; machined, acid‐etched TiZr alloy, modMA; machined, sandblasted, acid‐etched TiZr alloy, modSLA; and micro‐grooved titanium aluminum vanadium alloy, TAV MG) in an experimental human model.

Material and methods

Custom‐made discs were mounted in individual intraoral splint housings and worn by 16 volunteers for 24 h. The safranin staining assay, isothermal microcalorimetry (IMC), and SEM were applied before and after surface cleaning.

Results

The hydrophilic surfaces modMA and modSLA with greater surface micro‐roughness exhibited significantly more biofilm than the hydrophobic surfaces TAV MG and M. The standardized cleaning procedure substantially reduced the biofilm mass on all surfaces. After cleaning, the IMC analyses demonstrated a longer lag time of the growth curve on TAV MG compared to modSLA. Inter‐ and intraindividual variations in biofilm formation on the titanium discs were evident throughout the study.

Conclusions

Surface hydrophilicity and roughness enhanced biofilm formation in vivo, whereas surface topography was the most influential factor that determined surface cleanability. While the grooved surface retained larger amounts of initial biofilm, the machined surface was easier to clean, but proliferation indicated by increased metabolic activity (growth rate) in IMC occurred despite mechanical biofilm removal.
The antibiotic of choice determined by antibiogram in maxillary sinus elevation surgery: a clinical study
Authors: Carreño Carreño Javier , Gómez‐Moreno Gerardo , Aguilar‐Salvatierra Antonio , Martínez Corriá Ramón , Menéndez López‐Mateos María Luisa , Menéndez‐Núñez Mario
Published: March 2016

Objectives

This study set out to make antibiograms of positive bacteria cultures in samples collected when performing maxillary sinus elevations to determine a specific and effective antibiotic in each case.

Material and methods

A total of 174 patients (90 women and 84 men) with a mean age of 55.92 years underwent 227 sinus elevations. As the membrane was lifted, a sample was collected from the maxillary sinus floor with a cotton swab and placed on a blood agar and chocolate agar culture to incubate for 48 h at 37°; the samples then underwent microbiological analysis. Antibiograms were made for each positive culture to identify the most sensitive antibiotic, which were regrouped according to their mechanism of action as: beta‐lactam (penicillins), beta‐lactam (cephalosporins), macrolides, quinolones, fosfomycin, aminoglycosides, or trimethoprim‐sulfamethoxazole.

Results

Of 227 cultures, 18.1% were bacteria‐positive. Of the germs, 45% were of the Streptococcus genus, most of which belonged to the Streptococcus viridans group (61.1%). The germs studied showed greater resistance to macrolides and greater sensitivity to penicillins, cephalosporins, and ciprofloxacin. The antibiotics that showed the greatest efficacy were as follows: ampicillin, amoxicillin–clavulanate, and ciprofloxacin.

Conclusions

On the basis of antibiograms of positive cultures, the antibiotics presenting the greatest efficacy against possible complications were as follows: ampicillin, amoxicillin–clavulanate, and ciprofloxacin. Clinically, the antibiograms proved useful as they allowed the prescription of specific antibiotics to resolve possible postoperative sinus infections.
A stratified analysis of the perioperative outcome of 17623 patients undergoing major head and neck cancer surgery in England over 10 years: Towards an Informatics‐based Outcomes Surveillance Framework
Authors: Nouraei S.A.R. , Mace A.D. , Middleton S.E. , Hudovsky A. , Vaz F. , Moss C. , Ghufoor K. , Mendes R. , O'Flynn P. , Jallali N. , Clarke P.M. , Darzi A. , Aylin P.
Published: March 2016

Objectives

To perform a national analysis of the perioperative outcome of major head and neck cancer surgery to develop a stratification strategy and outcomes assessment framework using hospital administrative data.

Design

A Hospital Episode Statistics N = near‐all analysis.

Settings

The English National Health Service.

Main outcome measures

Local audit data were used to assess and triangulate the quality of the administrative dataset. Within the national dataset, cancer sites, morbidities, social deprivation, treatment, complications, and in‐hospital mortality were recorded.

Results

Within local audit datasets, the accuracy of assigning newly‐derived Cancer Site Strata and Resection Strata were 92.3% and 94.2%, respectively. Accuracy of morbidities assignment was 97%. Within the national dataset, we identified 17 623 major head and neck cancer resections between 2002 and 2012. There were 12 413 males and mean age at surgery was 63 ± 12 years. The commonest cancer site strata were oral cavity (42%) and larynx–hypopharynx (32%). The commonest resection site was the larynx (n = 4217), and 13 211 and 11 841 patients had neck dissection and flap‐based reconstruction, respectively. There were prognostically significant baseline differences between patients with oromandibular and pharyngolaryngeal malignancy. Patients with pharyngolaryngeal malignancies had a greater burden of morbidities, lower socio‐economic status, fewer primary resections, and a sixfold increased risk of undergoing their major resection during an emergency hospital admission. Mean length of stay was 25 days and each complication linearly increased it by 9.6 days. There were 609 (3.5%) in‐hospital deaths and a basket of seven medical and three surgical complications significantly increased the risk of in‐hospital death. At least one potentially lethal complication occurred in 26% of patients. The risk of in‐hospital death in a patient with no potentially lethal complication was 1.1% and this increased to 6% with one potentially lethal complication, and to 15.1% if two potentially lethal complications occurred in one patient. Complex oral‐pharyngeal resections and pharyngolaryngectomies had the highest risks of complications and mortality.

Conclusion

Mortality following head and neck cancer surgery shows variation across different resection strata. We propose an Informatics‐based Framework for Outcomes Surveillance (IFOS) in Head and Neck Surgery for perpetual quality assurance, using the local hospital coding data or its collated destination, the national administrative dataset.
The role of time and species identities in spatial patterns of species richness and conservation
Authors: Hewitt Judi E. , Thrush Simon F. , Ellingsen Kari E.
Published: March 2016

Many conservation actions are justified on the basis of managing biodiversity. Biodiversity, in terms of species richness, is largely the product of rare species. This is problematic because the intensity of sampling needed to characterize communities and patterns of rarity or to justify the use of surrogates has biased sampling in favor of space over time. However, environmental fluctuations interacting with community dynamics lead to temporal variations in where and when species occur, potentially affecting conservation planning by generating uncertainty about results of species distribution modeling (including range determinations), selection of surrogates for biodiversity, and the proportion of biodiversity composed of rare species. To have confidence in the evidence base for conservation actions, one must consider whether temporal replication is necessary to produce broad inferences. Using approximately 20 years of macrofaunal data from tidal flats in 2 harbors, we explored variation in the identity of rare, common, restricted range, and widespread species over time and space. Over time, rare taxa were more likely to increase in abundance or occurrence than to remain rare or disappear and to exhibit temporal patterns in their occurrence. Space–time congruency in ranges (i.e., spatially widespread taxa were also temporally widespread) was observed only where samples were collected across an environmental gradient. Fifteen percent of the taxa in both harbors changed over time from having spatially restricted ranges to having widespread ranges. Our findings suggest that rare species can provide stability against environmental change, because the majority of species were not random transients, but that selection of biodiversity surrogates requires temporal validation. Rarity needs to be considered both spatially and temporally, as species that occur randomly over time are likely to play a different role in ecosystem functioning than those exhibiting temporal structure (e.g., seasonality). Moreover, temporal structure offers the opportunity to place management and conservation activities within windows of maximum opportunity.
Adoption and success rates of perineal procedures for fistula‐in‐ano: a systematic review
Authors: Kontovounisios C. , Tekkis P. , Tan E. , Rasheed S. , Darzi A. , Wexner S. D.
Published: March 2016

Aim

Several sphincter‐preserving techniques have been described with extremely encouraging initial reports. However, more recent studies have failed to confirm the positive early results. We evaluate the adoption and success rates of advancement flap procedures (AFP), fibrin glue sealant (FGS), anal collagen plug (ACP) and ligation of intersphincteric fistula tract (LIFT) procedures based on their evolution in time for the management of anal fistula.

Method

A PubMed search from 1992 to 2015. An assessment of adoption, duration of study and success rate was undertaken.

Results

We found 133 studies (5604 patients): AFP (40 studies, 2333 patients), FGS (31 studies, 871 patients), LIFT (19 studies, 759 patients), ACP (43 studies, 1641 patients). Success rates ranged from 0% to 100%. Study duration was significantly associated with success rates in AFP (P = 0.01) and FGS (P = 0.02) but not in LIFT or ACP. The duration of use of individual procedures since first publication was associated with success rate only in AFP (P = 0.027). There were no statistically significant differences in success rates relative to the number of the patients included in each study.

Conclusion

Success and adoption rates tend to decrease with time. Differences in patient selection, duration of follow‐up, length of availability of the individual procedure and heterogeneity of treatment protocols contribute to the diverse results in the literature. Differences in success rates over time were evident, suggesting that both international trials and global best practice consensus are desirable. Further prospective randomized controlled trials with homogeneity and clear objective parameters would be needed to substantiate these findings.
Translating colorectal cancer genetics into clinically useful biomarkers
Authors: Morley‐Bunker A. , Walker L. C. , Currie M. J. , Pearson J. , Eglinton T.
Published: March 2016

Colorectal cancer (CRC) is a major health problem worldwide accounting for over a million deaths annually. While many patients with Stage II and III CRC can be cured with combinations of surgery, radiotherapy and chemotherapy, this is morbid costly treatment and a significant proportion will suffer recurrence and eventually die of CRC. Increased understanding of the molecular pathogenesis of CRC has the potential to identify high risk patients and target therapy more appropriately. Despite increased understanding of the molecular events underlying CRC development, established molecular techniques have only produced a limited number of biomarkers suitable for use in routine clinical practice to predict risk, prognosis and response to treatment. Recent rapid technological developments, however, have made genomic sequencing of CRC more economical and efficient, creating potential for the discovery of genetic biomarkers that have greater diagnostic, prognostic and therapeutic capabilities for the management of CRC. This paper reviews the current understanding of the molecular pathogenesis of CRC, and summarizes molecular biomarkers that surgeons will encounter in current clinical use as well as those under development in clinical and preclinical trials. New molecular technologies are reviewed together with their potential impact on the understanding of the molecular pathogenesis of CRC and their potential clinical utility in classification, diagnosis, prognosis and targeting of therapy.
Primary mediastinal synovial sarcoma with subsequent development of primary adenoid cystic carcinoma of lung presenting as superior vena cava syndrome
Authors: Madabhavi Irappa , Patel Apurva , Anand Asha , Panchal Harsha , Parikh Sonia
Published: March 2016

Primary mediastinal sarcomas are aggressive tumors with a very rare incidence. This report describes the case of a 35 year old male patient who presented with acute symptoms of dyspnoea, facial puffiness, engorged neck veins and hoarseness of voice. With the clinical picture consistent with the superior vena caval (SVC) syndrome, the patient was investigated with computed tomography of the chest. This revealed a large soft tissue density mass lesion compressing the SVC along with other critical superior mediastinal structures. Histopathological evaluation of the mass revealed features consistent with a soft tissue sarcoma and positive staining was observed for vimentin and S‐100. Cytogenetic analysis by fluorescent in‐situ hybridization (FISH) demonstrated the t(X: 18) translocation. Thus diagnosis was established as primary mediastinal synovial sarcoma. Patient was treated with three‐cycles of neo‐adjuvant (ifosfamide 2400mg/m2 on days 1‐5 and doxorubicin 37.5 mg/m2 on days 1 & 2) chemotherapy, to which there was a partial response as per the RECIST criteria. Surgical excision of the mediastinal mass was performed, and further post‐operative treatment with adjuvant chemo‐radiotherapy was provided. Patient was under regular surveillance at our clinic and remains free of symptoms one‐year after treatment completion. But after 14 months of treatment completion patient again had symptoms of progressive dyspnea, hoareness of voice and mild facial puffiness over a period of 2 months. On further investigating he was found to have right‐sided centrally located mass with cystic and necrotic changes with extension and compression of trachea, SVC, right upper lobe bronchus and its branches. Histopathological examination of the biopsy from the lesion revealed adenoid cystic carcinoma of the lung. Rest of the metastatic work up was within normal. Immunohistochemistry of the specimen revealed c‐Kit positivity. In view of the morbid second surgery he was put on Imatinib 400mg once a day and celecoxib 200mg twice a day. After 4 months patient had partial response and presently continuing with the same regimen. Extensive literature search didn't reveal much information on combined primary mediastinal sarcoma and adenoid cystic carcinoma of lung.
Solid organ transplant patients: are there opportunities for antimicrobial stewardship?
Authors: So Miranda , Yang Daisy Yu , Bell Chaim , Humar Atul , Morris Andrew , Husain Shahid
Published: March 2016

Objective

Rising incidence of Clostridium difficile and multidrug‐resistant organisms' infections and a dwindling development of new antimicrobials are an impetus for antimicrobial stewardship in organ transplant recipients. We sought to understand antimicrobial prescribing practices and identify opportunities for interdisciplinary collaboration among the transplant, antimicrobial stewardship, and infectious diseases teams.

Methods

In 2013, two assessors conducted four real‐time audits on all antimicrobial therapy in transplant patients, assessing each regimen against stewardship principles established by the Centers for Disease Prevention and Control, supplemented by applicable transplant‐specific infection guidelines. Chi‐square test was used to compare stewardship‐concordant and stewardship‐discordant audit results relative to transplant infectious diseases consultation.

Results

Analysis was performed on 176 audits. Fifty‐eight percent (103/176) received at least one antimicrobial, of which 69.9% (72/103) were stewardship‐concordant. Infections were confirmed or suspected in 52.3% (92/176). Of those, 98.9% (91/92) received antimicrobials, and 41.8% (38/91) were prescribed by transplant clinicians. Infectious diseases consultation was associated with more stewardship‐concordant prescriptions (78.5% vs. 59.6%, p = 0.03). The most common stewardship‐discordant categories were lack of de‐escalation, empiric antimicrobial spectrum being too broad, and therapy duration being too long.

Conclusions

Opportunities exist for antimicrobial stewardship in transplant recipients, especially those who do not require infectious diseases consultation.