bluuebunny/crossref_metadata_2025 huggingface dataset:
028 How Do Clinicians Like and Understand Trustworthy Guidelines? Randomised Controlled Trial Using Clickers in Educational Sessions
Authors: Vandvik P , Brandt L , Kristiansen A , Alonso P , Agoritsas T , Akl E , Guyatt G
Published: August 2013

Background

Clinical practice guidelines (CPG) often have shortcomings in presentation formats that limit dissemination at the point of care. As part of the DECIDE project we have developed multilayered CPG presentation formats. Comprehensive user-testing of the formats has provided us with alternative presentation formats now ready for randomised trials but also an important insight: Insufficient conceptual understanding of guideline methodology (e.g. strength of recommendations and quality of evidence) may hamper application of CPG recommendations in practice.

Objectives

To determine physicians’ understanding, attitudes and preferences concerning trustworthy guidelines in traditional and new presentation formats (DECIDE A and B).

Methods

In this randomised controlled trial we will recruit 100 physicians attending a standardised lecture with 3 components: 1) presentation of clinical scenario, 2) explanations of key concepts of trustworthy CPG (e.g. GRADE, AGREE II) and 3) presentation of a current trustworthy CPG relevant to the scenario, displayed in traditional PDF format and DECIDE A and B formats. Throughout the lecture participants will answer questions with ‘Clickers’ and be randomly assigned to alternative presentation formats by concealed allocation and blinding, through the use of eyepatches.

Results

We will present results from the trial at the conference.

Discussion

If our approach of integrating randomised trials into educational sessions is feasible and provides valid results we will conduct multiple such trials in DECIDE.

Implications for Guideline Developers and Users

Optimised GL presentation formats and sufficient conceptual understanding, as researched in this trial, should facilitate the uptake of trustworthy CPG and application of research evidence in practice.
035 What Do Guideline Appraisal Tools Assess? A Systematic Review
Authors: Siering U , Eikermann M , Hausner E , Hoffmann-Eber W , Neugebauer E
Published: August 2013

Background

Clinical practice guidelines should provide a rational basis for healthcare decisions; however, their quality is often poor.

Objectives

To systematically identify and describe guideline appraisal tools and draw conclusions for guideline appraisal.

Methods

We conducted a systematic search in MEDLINE, EMBASE and the Cochrane Library for English and German-language guideline appraisal tools published after 1995. Reference lists of included publications were also screened. Dimensions of guideline quality were then generated from these publications and from articles by Cluzeau 1999, Graham 2000 and Vlayen 2005. Finally, the questions contained in the appraisal tools were allocated to the quality dimensions and summarised.

Results

Overall, 40 appraisal tools were included and 13 quality dimensions identified. The main focus was the identification, assessment and presentation of evidence in guidelines. Questions on dealing with norms and values in guideline development, patient involvement, conflicts of interest, or implementation of guidelines into clinical practice were rare. The tools often assessed the appropriate documentation of the guideline development process (e.g. reporting of the search strategy), without addressing the appraisal of content of the development process (e.g. appropriateness of the search strategy) and the appraisal of clinical content.

Discussion

Because many appraisal tools do not contain questions on norms and values or on potential conflicts of interest of guideline authors, important aspects potentially influencing the reliability of guidelines are not covered. In addition, an appraisal of content of the guideline development process and an appraisal of clinical content are often lacking.
046 Guideline Development Tool (GDT) – Web-Based Solution for Guideline Developers and Authors of Systematic Reviews
Authors: Brozek J , Akl E , Falck-Ytter Y , Kunstman P , Meerpohl J , Mustafa R , Nowak A , Oxman A , Santesso N , Wiercioch W , Schünemann H
Published: August 2013

Background

Guideline developers and other health care decision makers benefit from following a structured process of specifying the health care questions they intend to answer and the outcomes of interest, assessing the confidence in the available evidence, gathering information about the values and preferences of the target population, and presentation of their results and decisions to the target users. Many guideline developers use the GRADE Profiler (GRADEpro) software used to conduct this work.

Context

GRADE’s approach is currently being further defined in the DECIDE (Developing and Evaluating Communication Strategies to Support Informed Decisions and Practice Based on Evidence) project.

Description of Best Practice

The Guideline Development Tool (GDT) is the extension of the GRADE Profiler (GRADEpro) software. The GDT provides an integrated platform-independent web-based solution for health care decision makers offering support for the whole process of making decisions and developing recommendations including question formulation, generation and prioritisation of outcomes, support for teamwork, management of potential conflicts of interest, presentation of results (including the functionality of GRADEpro) and decision support. We tested the software with individual users and in workshops as well as in guideline development processes.

Lessons for Guideline Developers, Adaptors, Implementers, and/or Users

Following a structured and systematic process, transparency and clarity of presentation facilitates the use of results of systematic reviews and facilitates development, updating and adaptation of evidence-based recommendations and decisions. Storing all information in a uniform, structured, transparent and annotated way also greatly facilitates updating and adaptation of systematic reviews and guidelines.
054 Transforming Evidence From Multiple Guidelines Into User Friendly Clinical Practice Tools For Remote Cancer Treatment-Related Symptom Management: The Costars Project
Authors: Stacey D , Carley M , Harrison M
Published: August 2013

Objectives

To transform evidence from guidelines for clinical practice tools for remote management of patients experiencing symptoms related to cancer treatment. Clinical practice protocols are defined as user-friendly knowledge translation tools to support patient care. These tools narrow the know-do gap by presenting the best available evidence from guidelines while using a format that is sensitive to how nurses think and what nurses do.

Methods

Mixed methods descriptive study guided by CAN-IMPLEMENT©. The process involved: a) conducting a systematic search for guidelines; b) developing symptom-specific protocols using evidence from quality appraised clinical practice guidelines; c) reaching consensus on the clinical practice protocol template, and d) validating the clinical practice protocols.

Results

Clinical practice protocols were developed and validated for 13 symptoms using 42 clinical practice guidelines with a median of 3 guidelines per protocol (range 1 for bleeding to 7 vomiting). For the first two protocols, source guideline AGREE rigour subscale ratings ranged from 8% to 86% (median 60.1; diarrhoea; 40.5 fever). The protocols were developed using guidelines, symptom severity questions included the Edmonton Symptom Assessment System, and iterative feedback from practicing nurses. Usability testing revealed: high readability, just the right amount of information, and appropriate terms. Access to protocols needs to be tailored to individual practices (e.g. electronic application, access to paper-based versions). Nurses requested training and support to implement them.

Discussion

These tools, created from guidelines, transform evidence into user-friendly protocols for use by nurses when guiding patients at home to better manage their cancer treatment-related symptoms.
055 Use of Non-Randomised Studies In The Guideline Process: The GRADE Approach
Authors: Santesso N , Mustafa R , Schunemann H
Published: August 2013

Background

The GRADE approach to guideline development requires a review of the best available evidence which includes randomised controlled trials (RCTs) and non-randomised studies (NRS).

Objectives

Describe the use of NRS as a replacement, a sequence, or a complement for RCTs, in a World Health Organization guideline using the GRADE approach.

Methods

We searched the literature using no study type limits for the effect of screening and treatment of precancerous lesions on patient or population important outcomes and for baseline risks. We assessed quality of the evidence using GRADE.

Results

Depending on the outcomes, we found few to no RCTs. When there was low/very low overall quality evidence from RCTs, we used NRS studies with no independent control groups to compare proportions between groups and calculate a relative effect of treatment and this evidence replaced the RCT evidence with similar/higher quality evidence. We found no evidence in RCTs for long-term outcomes, such as spontaneous abortion. Therefore, we used data from NRS (cohort studies) for premature delivery (a surrogate) to provide sequential evidence. For evidence about baseline risk of precancerous lesions and other outcomes, we used NRS a complement to the RCT data.

Discussion

Data from NRS provided evidence in three ways. One key criterion to consider when grading this evidence is indirectness due to indirect comparisons, surrogate outcomes or varying population risks.

Implications for Guideline Developers/Users

Guideline developers can use GRADE and these methods when there is no evidence or low/very low quality evidence from RCTs.
INDUCED NANOCRYSTALLIZATION OF DEXTROSE MONOHYDRATE
Authors: JOHNSON IRUDAYARAJ , RAJ B. KANICKAI , SIVAGAMI V. , SELVI NAGA PONDY
Published: August 2013

Modern ultrasound induction is very much useful in crystallization process. It uses piezoelectric transducers or quartz crystals to convert mechanical waves to electrical signals and vice versa. Growth of a crystal is environment dependent. The characteristics of grown crystals depend on impurities, temperature, preparation of the solution and mechanical agitation. The properties and size of a crystal can be tailored by controlling any one or all the above factors. The most interesting fact is that the ultrasound influences the properties and size of a crystal. It is found that the characteristics are improved and tailored for a specific need of the industry when a crystal is grown by radiating ultrasonic wave. In some cases, it produces nanocrystals. We used a device which generates the Ultrasonic wave of 15 MHz, which is applied to the crystal right from the time before nucleation till the crystal formation. The Dextrose monohydrate crystals are grown by conventional slow cool batch method. In the same slow cool batch method, Ultrasonic waves of 15 MHz are allowed to pass, influence the nucleation, crystal formation and growing process. The crystal formation process under the exposure of Ultrasound is allowed to continue for a sufficiently long time to yield the desired nanocrystals. The FTIR, UV, microhardness and SEM analysis are taken for the crystals with and without ultrasound.
VISUALIZING THE UPTAKE AND INTRACELLULAR VESICLE TRANSPORT OF CARBON NANOTUBES TOWARD THE PERINUCLEAR REGION INSIDE CELLS
Authors: LI JUN , KANG BIN , CHANG SHUQUAN , DAI YAODONG
Published: August 2013

We directly visualized the uptake and intracellular vesicle transport of shortened single walled carbon nanotubes in living cells through a dual-labeling system. With a stable labeling of fluorescein isothiocyanate and a pH-sensitive stacking of doxorubicin on carbon nanotubes, the location of internalized nanotubes inside the cell and the microenvironment especially the pH change of the nanotube-embedded vesicles could be monitored at the same time. Results showed that after internalization through endocytic pathway, carbon nanotubes tended to transport from the early endosomes to later acidic lysosomes and these vesicles moved along the microtubule track toward a perinuclear region where is a microtubule-organizing center. These results might provide a novel understanding for the intracellular interaction of carbon nanotubes and living cells.
INVERSION OF THE ELECTRICAL AND OPTICAL PROPERTIES OF PARTIALLY OXIDIZED HEXAGONAL BORON NITRIDE
Authors: NAYAK AVINASH P. , DOLOCAN ANDREI , LEE JONGHO , CHANG HSIAO-YU , PANDHI TWINKLE , HOLT MILO , TAO LI , AKINWANDE DEJI
Published: August 2013

By acoustically irradiating pristine, white, electrically insulating h- BN in aqueous environment we were able to invert its material properties. The resulting dark, electrically conductive h- BN (referred to as partially oxidized h- BN or PO- hBN ) shows a significant decrease in optical transmission (>60%) and bandgap (from 5.46 eV to 3.97 eV). Besides employing a wide variety of analytical techniques (optical and electrical measurements, Raman spectroscopy, SEM imaging, EDS, X-Ray diffraction, XPS and TOF-SIMS) to study the material properties of pristine and irradiated h- BN , our investigation suggests the basic mechanism leading to the dramatic changes following the acoustic treatment. We find that the degree of inversion arises from the degree of h- BN surface or edge oxidation which heavily depends on the acoustic energy density provided to the pristine h- BN platelets during the solution-based process. This provides a facile avenue for the realization of materials with tuned physical and chemical properties that depart from the intrinsic behavior of pristine h- BN .
FRACTAL CHARACTERISTICS OF PHASE SPECTRUM OF EARTHQUAKE MOTION
Authors: SATO TADANOBU
Published: August 2013

The purpose of this research is to make clear the phase spectrum characteristic of earthquake motion. After the introduction of past researches we introduce the concept of fractional Brownian process (FBP). A simple method is proposed to determine the Hurst index and the variance of a given process characterized by the FBP. We find that the phase characteristic of earthquake motion can be expressed by this process which is a non-stationery function of the circular frequency with a constant correlation coefficient. Using several observed earthquake motion we demonstrate this fact and show the efficiency of newly founded result to simulate realistic earthquake motion phase and also compare simulated earthquake motions with those of observed ones. We also simulate design response spectrum compatible earthquake motions by simulating the earthquake motion phase using the identified Hurst index and variance of the given earthquake motion. We investigate the effect of hypocenter distance on the variance and Hurst index of earthquake motion phase, as well as on the mean gradient of earthquake motion phase with respect to the circular frequency.
EEG analysis reveals widespread directed functional interactions related to a painful cutaneous laser stimulus
Authors: Markman T. , Liu C. C. , Chien J. H. , Crone N. E. , Zhang J. , Lenz F. A.
Published: August 2013

During attention to a painful cutaneous laser stimulus, event-related causality (ERC) has been detected in recordings from subdural electrodes implanted directly over cortical modules for the treatment of epilepsy. However, these studies afforded limited sampling of modules and did not examine interactions with a nonpainful stimulus as a control. We now sample scalp EEG to test the hypothesis that attention to the laser stimulus is associated with poststimulus ERC interactions that are different from those with attention to a nonpainful stimulus. Subjects attended to (counted) either a painful laser stimulus (laser attention task) or a nonpainful electrical cutaneous stimulus that produced distraction from the laser (laser distraction task). Both of these stimuli were presented in random order in a single train. The intensities of both stimuli were adjusted to produce similar baseline salience and sensations in the same cutaneous territory. The results demonstrated that EEG channels with poststimulus ERC interactions were consistently different during the laser stimulus versus the electric stimulus. Poststimulus ERC interactions for the laser attention task were different from the laser distraction task. Furthermore, scalp EEG frontal channels play a driver role while parietal temporal channels play a receiver role during both tasks, although this does not prove that these channels are connected. Sites at which large numbers of ERC interactions were found for both laser attention and distraction tasks (critical sites) were located at Cz, Pz, and C3. Stimulation leading to disruption of sites of these pain-related interactions may produce analgesia for acute pain.
Involvement of Potassium Channels in Vasorelaxant Effect Induced byValeriana prionophyllaStandl. in Rat Mesenteric Artery
Authors: Reis Milena Ramos , Oliveira Filho Abrahão Alves de , Rodrigues Lilia Simone Urzedo , Araújo Jaíse Paiva , Maciel Priscilla Maria Pereira , de Albuquerque Jamile Morais , Cehinel Filho Valdir , Cáceres Armando , Fregoneze Josmara Bartolomei , de Medeiros Isac Almeida , Silva Darizy Flávia
Published: August 2013

Assaysin vitroandin vivowere performed on extract from roots and leaves from theValeriana prionophyllaStandl. (VPR and VPF, resp.). In phenylephrine (1 μM) precontracted rings, VPR (0.01–300 μg/mL) induced a concentration-dependent relaxation (maximum response (MR) = 75.4 ± 4.0%, EC50= 5.97 (3.8–9.3)μg/mL,n=6]); this effect was significantly modified after removal of the endothelium (EC50= 39.6 (27.2–57.6)μg/mL,P<0.05). However, VPF-induced vasorelaxation was less effective compared to VPR. When rings were preincubated with L-NAME (100 μM) or indomethacin (10 μM), the endothelium-dependent relaxation induced by VPR was significantly attenuated (MR = 20.9 ± 2.3%, 34.2 ± 2.9%, resp.,P<0.001). In rings denuded endothelium, precontracted with KCl (80 mM), or in preparations pretreated with KCl (20 mM) or tetraethylammonium (1 or 3 mM), the vasorelaxant activity of VPR was significantly attenuated (MR = 40.0 ± 8.2,n=5; 50.5 ± 6.0%; 49.3 ± 6.4%; 46.8 ± 6.2%; resp.,P<0.01). In contrast, neither glibenclamide (10 μM), barium chloride (30 μM), nor 4-aminopyridine (1 mM) affected VPR-induced relaxation. Taken together, these results demonstrate that hypotension induced by VPR seems to involve, at least in part, a vascular component. Furthermore, endothelium-independent relaxation induced by VPR involves K+channels activation, most likely due to BKCachannels, in the rat superior mesenteric artery.
Validation of Two MODIS Aerosols Algorithms with SKYNET and Prospects for Future Climate Satellites Such as the GCOM-C/SGLI
Authors: Dim Jules R. , Takamura Tamio , Higurashi Akiko , Kathri Pradeep , Kikuchi Nobuyuki , Nakajima Takahashi Y.
Published: August 2013

Potential improvements of aerosols algorithms for future climate-oriented satellites such as the coming Global Change Observation Mission Climate/Second generation Global Imager (GCOM-C/SGLI) are discussed based on a validation study of three years’ (2008–2010) daily aerosols properties, that is, the aerosol optical thickness (AOT) and the Ångström exponent (AE) retrieved from two MODIS algorithms. The ground-truth data used for this validation study are aerosols measurements from 3 SKYNET ground sites. The results obtained show a good agreement between the ground-truth data AOT and that of one of the satellites’ algorithms, then a systematic overestimation (around 0.2) by the other satellites’ algorithm. The examination of the AE shows a clear underestimation (by around 0.2–0.3) by both satellites’ algorithms. The uncertainties explaining these ground-satellites’ algorithms discrepancies are examined: the cloud contamination affects differently the aerosols properties (AOT and AE) of both satellites’ algorithms due to the retrieval scale differences between these algorithms. The deviation of the real part of the refractive index values assumed by the satellites’ algorithms from that of the ground tends to decrease the accuracy of the AOT of both satellites’ algorithms. The asymmetry factor (AF) of the ground tends to increase the AE ground-satellites discrepancies as well.
A Novel Class of Anticancer Compounds Targets the Actin Cytoskeleton in Tumor Cells
Authors: Stehn Justine R. , Haass Nikolas K. , Bonello Teresa , Desouza Melissa , Kottyan Gregg , Treutlein Herbert , Zeng Jun , Nascimento Paula R.B.B. , Sequeira Vanessa B. , Butler Tanya L. , Allanson Munif , Fath Thomas , Hill Timothy A. , McCluskey Adam , Schevzov Galina , Palmer Stephen J. , Hardeman Edna C. , Winlaw David , Reeve Vivienne E. , Dixon Ian , Weninger Wolfgang , Cripe Timothy P. , Gunning Peter W.
Published: August 2013

The actin cytoskeleton is a potentially vulnerable property of cancer cells, yet chemotherapeutic targeting attempts have been hampered by unacceptable toxicity. In this study, we have shown that it is possible to disrupt specific actin filament populations by targeting isoforms of tropomyosin, a core component of actin filaments, that are selectively upregulated in cancers. A novel class of anti-tropomyosin compounds has been developed that preferentially disrupts the actin cytoskeleton of tumor cells, impairing both tumor cell motility and viability. Our lead compound, TR100, is effective in vitro and in vivo in reducing tumor cell growth in neuroblastoma and melanoma models. Importantly, TR100 shows no adverse impact on cardiac structure and function, which is the major side effect of current anti-actin drugs. This proof-of-principle study shows that it is possible to target specific actin filament populations fundamental to tumor cell viability based on their tropomyosin isoform composition. This improvement in specificity provides a pathway to the development of a novel class of anti-actin compounds for the potential treatment of a wide variety of cancers. Cancer Res; 73(16); 5169–82. ©2013 AACR.
Pertuzumab: Optimizing HER2 Blockade
Authors: Metzger-Filho Otto , Winer Eric P. , Krop Ian
Published: August 2013

Pertuzumab has been approved by the U.S. Food and Drug Administration for use in combination with trastuzumab and docetaxel for the first-line treatment of patients with advanced HER2-positive (HER2+) breast cancer. Pertuzumab is a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2 and inhibits heterodimerization of HER2 with other HER family members, including EGF receptor (EGFR), HER3, and HER4. The HER2–HER3 heterodimer is a robust activator of phosphoinositide 3-kinase (PI3K) pathway signaling and functions as the most transforming and mitogenic of the receptor complexes formed by the HER family of proteins; thus, blockade of HER2–HER3 likely represents the most relevant action of pertuzumab. In the seminal phase III study, patients with HER2+ metastatic breast cancer were randomized to receive trastuzumab and docetaxel, with or without pertuzumab: Addition of pertuzumab significantly prolonged progression-free survival with an increase of 6.1 months (12.4 vs. 18.5 months, respectively). In a subsequent analysis with 30 months of median follow-up, pertuzumab conferred a 34% reduction in the risk of mortality. Here, we review the mechanism of action of pertuzumab, the rationale for combining it with trastuzumab/pertuzumab, clinical data, and future directions for this work. Clin Cancer Res; 19(20); 5552–6. ©2013 AACR.
Developing Lipid Nanoparticle-Based siRNA Therapeutics for Hepatocellular Carcinoma Using an Integrated Approach
Authors: Li Leiming , Wang Rongqi , Wilcox Denise , Sarthy Aparna , Lin Xiaoyu , Huang Xiaoli , Tian Lu , Dande Prasad , Hubbard Robert D. , Hansen Todd M. , Wada Carol , Zhao Xiaobin , Kohlbrenner William M. , Fesik Stephen W. , Shen Yu
Published: August 2013

Successful siRNA therapeutics requires the optimal integration of multiple components, including an efficient delivery system, a disease indication that is appropriate for siRNA-based therapy, and a potent and nontoxic siRNA against a robust therapeutic target. Although all currently available delivery systems have limitations, it is important to recognize that a careful selection of the disease indication, therapeutic target, and siRNA molecule could partially compensate for deficiencies associated with the delivery system and makes it possible to advance a therapeutic siRNA regimen. In this study, we present the development of siRNA therapeutics for hepatocellular carcinoma using an integrated approach, including the development of an efficient lipid nanoparticle delivery system, the identification of a robust therapeutic target that does not trigger liver toxicity upon target knockdown, and the selection of potent and nonimmunogenic siRNA molecules against the target. The resulting siRNA-containing lipid nanoparticles produced significant antitumor efficacy in orthotopic hepatocellular carcinoma models, and, thus, represent a promising starting point for the development of siRNA therapeutics for hepatocellular carcinoma. Mol Cancer Ther; 12(11); 2308–18. ©2013 AACR.
High-Fat, High-Calorie Diet Promotes Early Pancreatic Neoplasia in the Conditional KrasG12D Mouse Model
Authors: Dawson David W. , Hertzer Kathleen , Moro Aune , Donald Graham , Chang Hui-Hua , Go Vay Liang , Pandol Steven J. , Lugea Aurelia , Gukovskaya Anna S. , Li Gang , Hines Oscar J. , Rozengurt Enrique , Eibl Guido
Published: August 2013

There is epidemiologic evidence that obesity increases the risk of cancers. Several underlying mechanisms, including inflammation and insulin resistance, are proposed. However, the driving mechanisms in pancreatic cancer are poorly understood. The goal of the present study was to develop a model of diet-induced obesity and pancreatic cancer development in a state-of-the-art mouse model, which resembles important clinical features of human obesity, for example, weight gain and metabolic disturbances. Offspring of Pdx-1-Cre and LSL-KrasG12D mice were allocated to either a high-fat, high-calorie diet (HFCD; ∼4,535 kcal/kg; 40% of calories from fats) or control diet (∼3,725 kcal/kg; 12% of calories from fats) for 3 months. Compared with control animals, mice fed with the HFCD significantly gained more weight and developed hyperinsulinemia, hyperglycemia, hyperleptinemia, and elevated levels of insulin-like growth factor I (IGF-I). The pancreas of HFCD-fed animals showed robust signs of inflammation with increased numbers of infiltrating inflammatory cells (macrophages and T cells), elevated levels of several cytokines and chemokines, increased stromal fibrosis, and more advanced PanIN lesions. Our results show that a diet high in fats and calories leads to obesity and metabolic disturbances similar to humans and accelerates early pancreatic neoplasia in the conditional KrasG12D mouse model. This model and findings will provide the basis for more robust studies attempting to unravel the mechanisms underlying the cancer-promoting properties of obesity, as well as to evaluate dietary- and chemopreventive strategies targeting obesity-associated pancreatic cancer development. Cancer Prev Res; 6(10); 1064–73. ©2013 AACR.
Acacetin InhibitsIn VitroandIn VivoAngiogenesis and Downregulates Stat Signaling and VEGF Expression
Authors: Bhat Tariq A. , Nambiar Dhanya , Tailor Dhanir , Pal Arttatrana , Agarwal Rajesh , Singh Rana P.
Published: August 2013

Angiogenesis is an effective target in cancer control. The antiangiogenic efficacy and associated mechanisms of acacetin, a plant flavone, are poorly known. In the present study, acacetin inhibited growth and survival (up to 92%; P < 0.001), and capillary-like tube formation on Matrigel (up to 98%; P < 0.001) by human umbilical vein endothelial cells (HUVEC) in regular condition, as well as VEGF-induced and tumor cells conditioned medium–stimulated growth conditions. It caused retraction and disintegration of preformed capillary networks (up to 91%; P < 0.001). HUVEC migration and invasion were suppressed by 68% to 100% (P < 0.001). Acacetin inhibited Stat-1 (Tyr701) and Stat-3 (Tyr705) phosphorylation, and downregulated proangiogenic factors including VEGF, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-2 (MMP-2), and basic fibroblast growth factor (bFGF) in HUVEC. It also suppressed nuclear localization of pStat-3 (Tyr705). Acacetin strongly inhibited capillary sprouting and networking from rat aortic rings and fertilized chicken egg chorioallantoic membrane (CAM; ∼71%; P < 0.001). Furthermore, it suppressed angiogenesis in Matrigel plugs implanted in Swiss albino mice. Acacetin also inhibited tyrosine phosphorylation of Stat-1 and -3, and expression of VEGF in cancer cells. Overall, acacetin inhibits Stat signaling and suppresses angiogenesis in vitro, ex vivo, and in vivo, and therefore, it could be a potential agent to inhibit tumor angiogenesis and growth. Cancer Prev Res; 6(10); 1128–39. ©2013 AACR.
Surgical Treatment and Prevention of Recurrence of Urethral Calculi Associated with Hairballs after Urethroplasty
Authors: Xie Linhai , Li Senkai , Li Qiang
Published: August 2013

Objectives: To evaluate technical aspects and outcome of preventing urethrocutaneous fistula and calculi recurrence in surgical treatment of urethral calculi associated with hairballs after urethroplasty. Patients and Methods: Sixteen patients who had urethral calculi associated with hairballs after urethroplasty underwent urethrolithotomy and trimming and epilation of the neourethra. While operating, we made a staggered incision of the skin and urethra, carefully su-tured the urethral incision, and covered it by well-vascularized tissue. A tube-in-tube stent method was performed on the latter 12 patients for better drainage of the exudates that accumulated in the urethra. Results: All calculi were successfully removed. Surgical site infection occurred in the last one of the former 4 patients and resulted in an urethrocutaneous fistula. There were no other complications. All patients were followed up for 2-7 years; no urethral stenosis or recurrence of calculi was observed, and remarkable reduction of urethral hair was obtained. Conclusions: Urethrolithotomy and trimming and epilation of the neourethra seem to be appropriate treatments for urethral calculi associated with hairballs after urethroplasty. Full attention should be paid to fistula prevention.
Orbital Inflammation Developing from Epidemic Keratoconjunctivitis in an Adult
Authors: Kim Sung In , Lee Kyeong Wook
Published: August 2013

Introduction: We report a rare case of epidemic keratoconjunctivitis (EKC) that developed into an orbital inflammation in an adult. Case Presentation: A 67-year-old Korean man, who had been diagnosed with EKC and treated for conjunctival injection and chemosis in the right eye for 4 days, was referred to Oculoplastics as orbital cellulitis was suspected. At the point of referral, clinical features such as decreased visual acuity, severe eyelid swelling, chemosis, follicles, corneal edema, limitations in lateral eye movement, and diplopia were observed in the right eye. Orbital cellulitis was suspected according to orbital computed tomography scan images, but there was no response to systemic antibiotics. Systemic steroid was administered instead, and then his symptoms and signs started to improve. The final diagnosis of this patient was orbital inflammation related to EKC based on the facts that there was no response to antibiotics, that he presented with contralateral symptoms and signs, that pseudomembrane formation occurred in both eyes, and that the symptoms resolved completely after 2 weeks. Conclusion: Clinicians need to consider the possibility of orbital inflammation developing from EKC, even in an adult patient, and treat the patient properly if the EKC symptoms and signs, such as conjunctival injection and follicles, are accompanied with symptoms and signs similar to orbital cellulitis.
Outcomes After Primary Transcatheter Therapy in Infants and Young Children With Severe Bilateral Peripheral Pulmonary Artery Stenosis
Authors: Cunningham Jonathan W. , McElhinney Doff B. , Gauvreau Kimberlee , Bergersen Lisa , Lacro Ronald V. , Marshall Audrey C. , Smoot Leslie , Lock James E.
Published: August 2013

Background—

Angioplasty and stent implantation have become accepted therapies for isolated peripheral pulmonary stenosis, and have been shown to increase vessel diameter and reduce right ventricular (RV) pressure acutely in patients with pulmonary artery (PA) stenosis. The purpose of this study was to assess long-term outcomes after primary transcatheter therapy for peripheral pulmonary stenosis.

Methods and Results—

We studied 69 patients who underwent primary transcatheter intervention for severe isolated peripheral pulmonary stenosis at ≤5 years of age. Genetic/syndromic diagnoses included Williams syndrome (n=23), non-Williams familial arteriopathy (n=12), and Alagille syndrome (n=3). At the initial PA intervention, median RV:aortic pressure ratio decreased from 1.00 to 0.88 (median decrease, 0.18;
P
<0.001). Patients with a higher preintervention RV:aortic pressure ratio had a greater reduction (
P
<0.001). During follow-up (median, 8.5 years), 10 patients died, 5 from complications of PA catheterization (all before 1998). Thirteen patients underwent surgical PA intervention, most within 1 year and along with repair of supravalvar aortic stenosis. Freedom from any PA reintervention was 38±6% at 1 year and 22±6% at 5 years. The median RV:aortic pressure ratio decreased from 1.0 at baseline to 0.53 at the most recent catheterization (
P
<0.001), and 82% of patients with available clinical follow-up were asymptomatic.

Conclusions—

Transcatheter therapy for infants with severe peripheral pulmonary stenosis has become safer, regardless of genetic condition. Coupled with reintervention and surgical relief in selected cases, RV:aortic pressure ratios decrease substantially and most patients are asymptomatic at late follow-up.
Pre-modern Chinese Sources in the National History of Brunei: The Case of Poli
Authors: Kurz Johannes L.
Published: August 2013

Abstract

The article deals with the appropriation of pre-modern Chinese sources by R. Nicholl and others for the national history of Brunei. It provides an analysis of the relevant sources and argues that Poli, a country described in the Chinese texts, was not a precursor of Brunei.
Cultivating Plantations and Subjects in East Timor: A Genealogy
Authors: Shepherd Christopher J. , McWilliam Andrew
Published: August 2013

Abstract

This article traces the emergence and institutionalization of plantation systems and cash crops in East Timor over two centuries. It examines the continuities, ruptures and shifting politics across successive plantation styles and political regimes, from Portuguese colonialism through Indonesian occupation to post-colonial independence. In following plantation agriculture from its origins to the present, the article explores how plantation subjects have been formed successively through racial discourse, repressive discipline, technical authority and neoliberal market policies. We argue that plantation politics have been instrumental in reproducing the class distinctions that remain evident in East Timor today.
ARCHAEOLOGY AND LATE ANTIQUE SOCIAL STRUCTURES
Authors: Sodini Jean-Pierre
Published: August 2013

The archaeological remains of late antique sites can be interpreted in terms of what they can tell us about ancient social structures. This is more straightforward when examining the social structures of the upper classes, who possessed the attributes that allow them to be recognised as such. These attributes occur on a Mediterranean-wide basis and include lavishly decorated residences (in both urban and rural environments), monumental funerary structures within churches, splendid garments, precious table wares and implements, and the insignia of rank in the form of jewellery such as gold brooches, fibulae, or belt buckles. The middle class is also traceable in the cities (mostly in the form of craftsmen) and in the countryside, where small landowners and peasants could share similar lifestyles, marked in some regions (such as the Near East and Asia Minor) by conspicuous levels of wealth. However, the lives of these middle classes could change abruptly, casting them into poverty and consequently making them difficult to trace archaeologically. Nonetheless, judicious interpretation of the material remains in tandem with the evidence of documentary and epigraphic sources allows us to make some suggestions as to the social structures of Late Antiquity.
SOME ASPECTS OF THE TRANSFORMATION OF THE ROMAN DOMUS BETWEEN LATE ANTIQUITY AND THE EARLY MIDDLE AGES
Authors: Polci Barbara
Published: August 2013

This essay concerns some aspects of the transformation of the Late Roman domus into the Early Medieval house and focuses on the spaces designed for reception and entertainment. First, I will consider the use and the development of the reception areas of wealthy houses, and their relationship with the growth in private patronage in Late Antiquity. Second, I will examine the transformation of this late antique model of elite housing into the new type of upper-class dwellings that emerged in Early Medieval Italy. In particular, I will focus on the transferral of reception halls and banqueting chambers to the upper story, and on the social and architectonic implications of this feature.
LATE ANTIQUE URBAN TOPOGRAPHY: FROM ARCHITECTURE TO HUMAN SPACE
Authors: Lavan Luke
Published: August 2013

Writing about the late antique city is dominated by topographical mapping, architectural studies and site syntheses. These approaches operate within a conception of space as the location of points within an imaginary grid. However, other notions of space exist. This paper proposes a move away from the location and description of physical remains towards a study of human spatiality. It also seeks to re-establish the study of topography at a general, rather than site-focused level. The limitations of existing approaches and the needs of late antique evidence are explored. An alternative topographical approach is suggested, based on studying ‘activity spaces’ (human activities in their total material setting) instead of simple buildings. This gives special prominence to texts, but seeks to combine all kinds of evidence. The methodological issues involved in doing this are considered. Possible implications for archaeological field practice are also explored.
THE URBAN IDEAL AND URBAN PLANNING IN BYZANTINE NEW CITIES OF THE SIXTH CENTURY AD
Authors: Zanini Enrico
Published: August 2013

Archaeological evidence and historical texts can be combined to distinguish some of the physical characteristics of Byzantine cities of the 6th c. A.D. They can also be used to define a common conceptual model which Byzantine people of the 6th c. recalled when they pronounced the word polis, either when they were defining an existing settlement or when they were planning a new city. This paper considers in particular four cities that were built anew or completely rebuilt in this time. The survival of the idea of the city in the 6th c. East also appears to be significant in understanding the preservation and renewal of this concept in the West Mediterranean, after the dark centuries of the Early Middle Ages.
DECLINE AND FALL? STUDYING LONG-TERM CHANGE IN THE EAST
Authors: Whittow Mark
Published: August 2013

With ‘decline and fall’ no longer a satisfactory model for long-term change in the Late Antique Near East (400-800 A.D.), attention has shifted to alternatives, here dubbed the ‘Fiscal’ model and the ‘Intensification and Abatement’ model. In the light of new evidence which makes the fiscal model less persuasive, that of intensification and abatement is attracting growing attention. However, its practical application will require the sort of longterm multi-period, and multi-disciplinary regional projects that have become very hard to organise under current UK funding arrangements.
REHABILITATING THE GREAT ESTATE: ARISTOCRATIC PROPERTY AND ECONOMIC GROWTH IN THE LATE ANTIQUE EAST
Authors: Sarris Peter
Published: August 2013

This article argues that recent emphasis on late antique economic expansion in the eastern Mediterranean and the prosperity of the peasantry of the East Roman empire has led historians to underestimate the economic importance of great estates owned by members of the imperial service aristocracy. This tendency has been exacerbated by the misleading testimony of early Byzantine saints’ lives, and an assumption that great estates were inherently autarchic and economically regressive. Rather, the evidence of the papyri and imperial legislation on the colonate would suggest that such great estates were highly commodified and monetised enterprises that contributed to economic growth.
THE ARCHAEOLOGY OF PILGRIMAGE IN LATE ANTIQUE ALBANIA: THE BASILICA OF THE FORTY MARTYRS
Authors: Mitchell John
Published: August 2013

Holy sites were one of the defining features of the landscape of Late Antiquity, frequented by the faithful, who would often travel considerable distances to make their devotions. Despite the widespread recognition by scholars of the importance of pilgrimage in Late Antiquity, study of this phenomenon tends to focus on Jerusalem and Rome together with a small selection of other major pilgrimage centres. This paper draws attention to a previously unrecognised pilgrimage site at Saranda in present day Albania, and suggests that secondary cult foci, which could have exceptional architectural elaboration, played an important role in the regional landscape.
VALLEY AND VILLAGE IN LATE ROMAN CYPRUS
Authors: Rautman Marcus
Published: August 2013

Recent investigations of Roman society and economy have sought to recover the histories of the varied provinces and their rural populations, whose circumstances and lifestyles remain poorly understood. The need is especially acute for Cyprus, which occupied an important place in the production and exchange networks of the East Mediterranean. A generation of archaeological survey work has assembled much basic information about this island landscape, and demonstrates that many parts of the Cypriot countryside were well integrated into the economy of the late empire. Analysis of the Vasilikos valley and the village at Kalavasos-Kopetra provides a detailed view of rural life and its transformation during Late Antiquity.
LATE ROMAN VILLA PLANS: THE DANUBE-BALKAN REGION
Authors: Mulvin Lynda
Published: August 2013

This paper examines the development of the architectural plan of the Late Roman villa in the Danube-Balkan region. It firstly considers questions relating to the definition of the Roman villa, then presents a methodology for establishing a typology, before classifying villas across a large geographical area. Finally, an attempt is made to explain the chronological and geographical distribution of different plans in relation to local conditions and wider historical phenomena.
MONASTERIES AS RURAL SETTLEMENTS: PATRON-DEPENDENCE OR SELF-SUFFICIENCY?
Authors: Brenk Beat
Published: August 2013

This paper is an examination of the textual and archaeological evidence for the economic nature of late antique monasteries. It considers to what extent monasteries were dependent on patronage, and to what extent they engaged in agriculture and other productive activities, and so were linked economically to the landscapes which surrounded them. Sites in Egypt and especially the Levant are examined, with literary and papyrological evidence from both East and West
A DE-ROMANISED LANDSCAPE IN NORTHERN GAUL: THE SCARPE VALLEY FROM THE 4TH TO THE 9TH CENTURY A.D.
Authors: Louis Etienne
Published: August 2013

This paper illustrates the evolution of settlement types in a small territory between Antiquity and the Medieval period. During the Early and Mid Roman periods, the area was densely and uniformly covered by numerous modest rural estates, in a way that differs from the ‘classical’ villa pattern. Many of these remained active until the 4th c. During the 5th c., small villages of ‘Germanic’ type replaced scattered settlements. This clustering of rural population was accompanied by a change to a landscape consisting of clearings and uncultivated areas. In the new villages, Early Medieval properties, in which a quadrangular ditched enclosure contained scattered structures such as timber buildings, sunken huts, and storage pits, were not replaced by the type of dwelling associated with the ‘Medieval’ village until the 11th or 12th c.
CONTINUITY AND CHANGE IN THE MACEDONIAN COUNTRYSIDE FROM GALLIENUS TO JUSTINIAN
Authors: Dunn Archibald
Published: August 2013

A history of the countryside in Late Antiquity that speaks of real terrains or regions, and thus confronts the shortcomings of written sources, remains elusive. Strategies based upon archaeology allow progress, but interpretation of the results remains problematic. However, if we collate the results of all kinds of fieldwork, the archaeology of Late Roman Macedonia now offers several case-studies which allow us to examine the forms and distributions of rural settlements of varying status. An assessment of the relationships between these settlements and their resource bases, together with the military, fiscal, and urban institutions with which they interacted, allows a re-evaluation of general histories of the countryside and ultimately of ‘the city’.
BUILDING THE PAST: MONUMENTS AND MEMORY IN THE FORUM ROMANUM
Authors: Machado Carlos
Published: August 2013

Memory played a crucial role in the shaping of Late Roman political consciousness and identity. This is clear in the case of the city of Rome, where political, religious, and social transformations affected the way that the city’s inhabitants defined their relationship between themselves and with the imperial court. The area of the forum Romanum was intimately related to Rome’s history, and was therefore particularly appropriate for the construction of different ‘Roman memories’. The aim of this article is to discuss how the monuments built or restored in this area helped to define these memories and turn the past into a political argument.
FORA AND AGORAI IN MEDITERRANEAN CITIES DURING THE 4TH AND 5TH C. A.D.
Authors: Lavan Luke
Published: August 2013

This article reviews the nature of fora and agorai during the late 3rd–5th c. A.D., and investigates the material appearance and everyday functions of these spaces. It revises the thesis of T. Potter’s Towns in Late Antiquity, through drawing upon a wider range of archaeological evidence and literary sources, which provide vivid details about everyday activities. It is argued that in many cities, especially in the East, fora/agorai were still monumental public squares with familiar public functions, and that the definitive eclipse of civic plazas, departing from earlier models of Mediterranean urbanism, comes later than has often been thought, in the 6th and 7th c.
DARK AGE ROME: TOWARDS AN INTERACTIVE TOPOGRAPHY
Authors: Cooper Kate , Hillner Julia , Leyser Conrad
Published: August 2013

This paper represents a report on work in progress at the University of Manchester’s Centre for Late Antiquity. The goal of our research is to open a new chapter in research on late ancient and Early Medieval Rome, through the systematic collation and diffusion of relatively neglected sources, in particular the Roman gesta martyrum. They are not usually considered as a source for the social history of the city, because of their transparently tendentious character. Yet the gesta are our best witness to the ebullient of the Roman laity, on whose patronage the ecclesiastical hierarchy continued to depend. We hope to make the gesta more widely accessible, and to facilitate their cross-referencing with other kinds of source; our method is to combine the tools of traditional scholarship with contemporary digital technologies, the operation of which we briefly describe here.