Mw/Mn = 1.08), poly(2-hydroxyethyl 2-((2-chloropropanoyloxy)methyl)acrylate) (PHECPMA), was first prepared by RAFT homopolymerization of 2-hydroxyethyl 2-((2-chloropropanoyloxy)methyl)acrylate (HECPMA), a Cl-containing trifunctional acrylate. ATRP of methyl methacrylate was subsequently initiated by PHECPMA homopolymer to afford the target well-defined poly(2-hydroxyethyl acrylate)-graft-poly(methyl methacrylate) (PHEA-g-PMMA) graft copolymers (Mw/Mn ≤ 1.36) with 34 PMMA side chains and 34 pendant hydroxyls in PHEA backbone using CuCl/dHbpy as catalytic system. The critical micelle concentration (cmc) of the obtained graft copolymer was determined by fluorescence spectroscopy using N-phenyl-1-naphthylamine as probe while micellar morphologies in aqueous media were visualized by transmission electron microscopy. Interestingly, PHEA-g-PMMA graft copolymer could self-assemble into large compound micelles rather than common spherical micelles, which can encapsulate hydrophilic rhodamine 6 G and hydrophobic pyrene separately or simultaneously.A series of well-defined amphiphilic graft copolymer bearing a hydrophilic poly(2-hydroxyethyl acrylate) (PHEA) backbone and hydrophobic poly(methyl methacrylate) (PMMA) side chains was synthesized by successive reversible addition-fragmentation chain transfer (RAFT) polymerization and atom transfer radical polymerization (ATRP) through the grafting-from strategy. A well-defined PHEA-based backbone with Cl-containing ATRP initiating group in every repeated unit ( Researches on the self-assembly of block copolymers revealed that solvent type, ionic strengthen, conditions of micelle preparation, and molecular weight and composition of copolymers all posed significant influences on the aggregated morphology and critical micellar concentration (cmc)9. However, until now most studies focused on linear block copolymers; meanwhile the architecture of copolymers has great impact on their self-assembly properties11. Nonlinear copolymers would display fundamentally different properties compared to the linear copolymers15.The self-assembly of amphiphilic copolymers16. Due to their confined and compact structures, graft copolymer possesses wormlike conformations, compact molecular dimensions, and notable chain end effects; and can form a variety of micellar morphologies in aqueous media23. Investigation on self-assembly of graft copolymer would deepen the understanding between the structure of copolymer and the morphology in aqueous media, which provides more information about controlling micellar morphologies and designing new nanomaterials25.Graft copolymer, consisting of backbone and side chains, are endowed with some unusual properties in solution owing to their nonlinear structure27, grafting-onto29, and grafting-from31 have been widely employed to prepare graft copolymers. The grafting-from strategy, in which polymeric backbone is prepared firstly and the side chains can be attached to the backbone by polymerization of another monomer, becomes the most popular and efficient approach for constructing well-defined graft copolymers with the help of reversible-deactivation radical polymerization (RDRP) including atom transfer radical polymerization (ATRP)34, reversible addition-fragmentation chain transfer (RAFT) polymerization36, and single-electron-transfer living radical polymerization (SET-LRP)38 because RDRP makes the control of molecular weight and molecular weight distribution of side chain become relatively easy.However, studies on graft copolymers have been restricted because the synthesis of well-defined graft copolymers with controlled molecular weights and narrow molecular weight distributions is a much tougher task compared to the synthesis of linear block copolymers. Until now, three common strategies of grafting-through40. In order to achieve the synthesis of this kind of amphiphilic graft copolymers, carboxyls are often introduced into the polymeric chain to maintain its hydrophilicity, of which poly(acrylic acid) (PAA) or poly(methacrylic acid) (PMAA) have been extensively employed to construct the hydrophilic backbones44. Peng et al. synthesized an amphiphilic graft copolymer bearing hydrophilic PAA backbone and hydrophobic poly(butyl methacrylate) side chains by a successive two-step ATRP and hydrolysis of a poly(methoxymethyl acrylate) backbone giving a hydrophilic PAA backbone finally41. Zhang et al. reported the synthesis of PAA-g-PMA amphiphilic graft copolymers whose hydrophilic backbones were obtained by selective hydrolysis of PtBA-g-PMA hydrophobic graft copolymers synthesized via sequential RAFT polymerization and ATRP42. However, the conspicuous drawback of the aforementioned work is that the polymeric chain needs to be chemically modified to afford the hydrophilic backbone.Recently, much attention has been paid to amphiphilic graft copolymers with hydrophilic backbones and hydrophobic side chains, which could display unique self-assembly morphology45, or be transformed into RDRP initiating groups followed by living/controlled radical polymerization of another monomer47, or be converted to alkynyls which is able to participate in a click reaction48. In 2014, our group developed a new trifunctional acrylate monomer, 2-hydroxyethyl 2-((2-chloropropanoyloxy)methyl)acrylate (HECPMA) comprising a polymerizable double bond, a halogen-containing RDRP initiating group (–OCOCH(CH3)Cl), and a hydroxyl simultaneously19. The RDRP initiating groups on the backbone are able to initiate ATRP or SET-LRP to introduce the side chains without affecting the pendant hydroxyls19, which means that amphiphilic graft copolymers with PHEA/PHEMA as the hydrophilic backbone can be obtained directly without the modification of the backbone.Poly(2-hydroxyethyl acrylate) (PHEA) and poly(2-hydroxyethyl methacrylate) (PHEMA) are also promising to be the hydrophilic backbone of graft copolymers compared to PAA. Nevertheless, PHEA/PHEMA have rarely been employed as hydrophilic backbone because the pendant hydroxyls are often utilized for connecting side chains; for example, the pendant hydroxyls of PHEA/PHEMA can initiate ring opening polymerization (ROP) to afford biodegradable polyester side chainsgraft-poly(methyl methacrylate) (PHEA-g-PMMA) was synthesized by sequential RAFT polymerization and ATRP through the grafting-from strategy as shown in Fig. g-PMMA. The cmc of PHEA-g-PMMA amphiphilic graft copolymer in aqueous media was measured by fluorescence spectroscopy and the micellar morphology was preliminarily explored using transmission electron microscopy (TEM).Herein, for the purpose of expanding the study on amphiphilic graft copolymers bearing PHEA as the hydrophilic backbone, a novel amphiphilic graft copolymer of poly(2-hydroxyethylacrylate)-19 comprising a polymerizable double bond, a -OCOCH(CH3)Cl ATRP initiating group, and a hydroxyl was thus employed as starting material in the current work to construct PHEA-g-PMMA well-defined amphiphilic graft copolymer by successive RDRP via the grafting-from strategy.MMA, a commonly used methacrylate monomer, has been widely polymerized by RDRP including ATRP, SET-LRP, and RAFT polymerization. Therefore, the most popular grafting-from approach can be employed in the present work to construct the well-defined amphiphilic graft copolymer consisting of hydrophilic PHEA backbone and hydrophobic PMMA side chains through RDRP of MMA initiated by the corresponding pendant initiating groups in the backbone. Since we prefer the well-defined amphiphilic graft copolymer bearing pendant hydroxyls in the backbone, PMMA side chains can not be connected onto the backbone by the usual ester linkage. HECPMA monomer19. The crude product was a kind of pink powder , which demonstrates the well-defined structure of homopolymer 2 prepared by RAFT polymerization of HECPMA monomer. The relative molecular weight of PHECPMA 2 homopolymer is 5,600 g/mol obtained from conventional GPC in DMF. The absolute molecular weight of PHECPMA 2 homopolymer  is determined to be 8,200 g/mol by using GPC/MALS, which is very close to the value  obtained from 1H NMR of the homopolymer Cl ATRP initiating groups.GPC curve of PHECPMA r Figure . Thus, tg-PMMA well-defined graft copolymer was constructed by ATRP of MMA via the grafting-from strategy, and the polymerization was initiated by the pendant -OCOCH(CH3)Cl initiating groups in PHECPMA 2 homopolymer.ATRP is one of the most useful and powerful RDRP process because of its mild reaction conditions, tolerance of most functional groups, and variety of monomers with precise control over molecular weight and molecular weight distribution. In the current case, the desired PHEA-g-PMMA 3 graft copolymers with various molecular weights were obtained by varying the feeding ratio of MMA monomer to the Cl-containing ATRP initiating group  and the polymerization time (20–50 min) as summarized in Table Mn,GPC ≥ 27,000 g/mol) are much higher than that of PHECPMA 2 homopolymer , this indicating the successful ATRP of MMA monomer. GPC curves of four PHEA-g-PMMA 3 graft copolymers are shown in Fig. Mw/Mn ≤ 1.36), which is also the characteristic of ATRP32. In the present work, a high feeding ratio of MMA monomer to ATRP initiating group (more than 100:1) along with a low conversion of monomer (<15%) were conducted in order to suppress the possible intermolecular coupling reaction50. Moreover, it can be seen from Table 3 increase with the extending of polymerization time while using the same feeding ratio of MMA to -OCOCH(CH3)Cl initiating group , and with the ascending of the feeding ratio of MMA to -OCOCH(CH3)Cl initiating group  while keeping the polymerization time constant, which are both the characteristic of ATRP32.ATRP of MMA was performed in the mixture of DMF/2-butanone v:v = 1:1) at 60 °C using CuCl/dHbpy as catalytic system. Four PHEA-:1 at 60 1H NMR were utilized to characterize PHEA-g-PMMA 3 graft copolymer. In comparison with FT-IR spectrum of PHECPMA 2 macroinitiator CO2). The minor peak at 3.95 ppm belongs to four protons of PHEA backbone . In particular, it should be pointed out that we can not find the trace of the proton resonance signal locating at 4.63 ppm attributed to one proton of -OCOCH(CH3)Cl initiating group  and 33.9 PMMA side chains.FT-IR and tor Fig. , the sigg-PMMA 3 graft copolymer, consisting of hydrophilic PHEA backbone and hydrophobic PMMA side chains, makes the graft copolymer capable of self-assembling in aqueous media so that the graft copolymer possesses a critical micelle concentration (cmc) to demonstrate the amphiphilicity. cmc of PHEA-g-PMMA 3 graft copolymer in aqueous media was determined by fluorescence spectroscopy using PNA as probe. PNA can display higher fluorescence activity in nonpolar surroundings and its fluorescence can be very easily quenched by polar solvents such as water; moreover, it is a more suitable fluorescent probe than pyrene in terms of reproducibility51. With the formation of micelles, PNA could be encapsulated into the hydrophobic core of micelles and its fluorescence intensity would increase with the raising of the concentration of polymer. Fluorescence emission spectra of PNA (360–540 nm) in aqueous solution of PHEA-g-PMMA 3c graft copolymer with different concentrations and the relationship of fluorescence intensity ratio  of PNA as a function of the concentration of copolymer 3c are both shown in Fig. 0 increases sharply when the concentration of copolymer 3c exceeds a certain value, indicative of the incorporation of PNA probe into the hydrophobic core of micelles51. Thus, cmc of PHEA-g-PMMA 3c graft copolymer is determined to be the intersection of two straight lines with a value of 2.69 × 10−6 g/mL. As summarized in Table cmc values of PHEA-g-PMMA 3 graft copolymers are in the range between 4.12 × 10−6 g/mL and 2.03 × 10−6 g/mL, which are much lower than those of low molecular weight surfactants and are comparable with those of polymeric amphiphiles52. Furthermore, one can observe from Table cmc of PHEA-g-PMMA 3 graft copolymer falls from 4.12 × 10−6 g/mL to 2.03 × 10−6 g/mL while increasing the molecular weight of PHEA-g-PMMA 3 graft copolymer, i.e. prolonging the length of hydrophobic PMMA side chains with the constant length of hydrophilic PHEA backbone.The amphiphilic nature of PHEA-g-PMMA 3 amphiphilic graft copolymer with a concentration of 0.01 mg/mL in aqueous media (above cmc) were visualized by TEM as shown in Fig. 3 graft copolymers with different lengths of PMMA side chains could assemble into spherical micelles. The hydrodynamic diameters (Dh) of these micelles obtained from dynamic light scattering (DLS) are found to be in the range from 122 nm to 294 nm  were chosen as the model guest molecules. Firstly, pyrene was used to test the encapsulation ability of micelles formed by copolymer 3c  for the hydrophobic compound in aqueous media. By using a UV/vis absorption standard curve at 337 nm, the loading content of pyrene is determined to be 26.4 μg pyrene per mg micelle23. As pyrene is insoluble in water, almost no UV absorption of pyrene appears in UV/vis absorption spectrum of aqueous solution of pyrene (after filtration to remove the insoluble pyrene) as shown in Fig. 3c . The absence of absorption signal at 536 nm  and a characteristic absorption peak of R6G appears at 536 nm. However, turning attention to R6G-containing aqueous micellar solution of PEG113-b-PS100 diblock copolymer 55, no same peak is detected in UV/vis absorption spectrum  reveals that there is no reaction between amine group of R6G and Cl of graft copolymer under current conditions, i.e. no R6G is covalently linked to the copolymer. Figure 56. Moreover, when R6G is dispersed in the aqueous micellar solution, the local concentration of R6G within micelles would be dramatically higher than that of pure aqueous solution of R6G with the same apparent concentration. Therefore, it is possible to confirm whether R6G is really located inside the micelles formed by copolymer 3c depending on the self-quenching property. The fluorescence intensity of R6G-containing aqueous micellar solution of copolymer 3c (olive line) is just 48% that of pure aqueous solution of R6G with the same apparent concentration of R6G (magenta line), as shown in Fig. 3c, rather than freely dissolved in water.It is well-known that fluorescence intensity of R6G in aqueous micellar solution is much lower than that in pure aqueous solution owing to the self-quenching property3c containing both pyrene and R6G simultaneously was prepared. Figure 3c (magenta line), while they are absent in UV/vis absorption spectrum of aqueous micellar solution of copolymer 3c (olive line), which illustrates the spontaneous encapsulation of both R6G and pyrene model loading agents within the core of micelles formed by copolymer 3c. Thus, all aforementioned details distinctly confirm our hypothesis that large compound micelles formed by copolymer 3c can separately or simultaneously uptake hydrophobic and hydrophilic compounds.Finally, aqueous micellar solution of copolymer g-PMMA well-defined amphiphilic graft copolymers with relatively narrow molecular weight distributions (Mw/Mn ≤ 1.36) through sequential RAFT polymerization and ATRP via the most popular grafting-from strategy, using a Cl-containing HECPMA trifunctional monomer as starting material. Post-polymerization functionality transformation is absent during the whole synthesis procedure because HECPMA monomer contains an ATRP initiating group so as to provide a well-defined backbone comprising a certain amount of initiating sites, furthermore affording the target graft copolymers with tunable length of side chains. The self-assembly behavior of PHEA-g-PMMA graft copolymer in aqueous media was visualized by TEM, which shows the formation of unusual large compound micelles able to separately or simultaneously uptake hydrophobic pyrene and hydrophilic R6G within the core. The multi-component structure of large compound micelles formed by PHEA-g-PMMA graft copolymer has the potential use as a multi-compartment delivery vehicle for the separated or simultaneous uptake of hydrophobic, hydrophilic compounds.In the current work, we display the detailed synthesis of PHEA-Supporting Information


Peer review system is like democracy: it is absolutely imperfect, but the best available. It allows criticism to articles, suggestions for improvement under different perspectives and allows the editor to make a fairer decision about the future of an article.The reviewer is the soul of a medical journal like International Brazilian Journal of Urology. He/she dictates the quality of publishing, the velocity by which each article reaches the reader, being a voluntary job that takes time. A good reviewer is rapidly identified by different magazines and is overloaded by many requests.A good reviewer is not necessarily famous in his/hers specialty, but a committed person that spends precious time without payment in order to evaluate a paper and to decide if its valuable enough to be published or if it needs improvements and guidance to authors.International Brazilian Journal of Urology has received 641 new submissions in 2016, added to other 275 that were revised and resubmitted. 456 reviewers participated in that task and it is important to nominate, as we have been doing in the past years, the most efficient and more collaborative.We created a formula by which this choice is not subjective and only based on the opinion of the Associated Editors:Reviewer score= (completed revisions/invitations)x R-scoreMedian time consumed for revisionThe result is multiplied by 100.R-score: given note that each AE gives to each revision (1= bad revision to 3-excelent review)Based on that formula we have elected the 5 most efficient reviewers of 2016 and we specially thanks them for their dedication:John Denstedt, University of Western Ontario London, ON, CanadaFabio Vicentini, Departamento de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, SP, BrasilRenato Pedro, UNICAMP, Campinas, SP, Brasil and Hospital Israelita Albert Einstein, São Paulo, SP, BrasilMarco Arap, Hospital Sírio Libanês, São Paulo, SP, BrasilLisias Castilho, Instituto de Ensino e Pesquisa do Hospital Sírio Libanês, São Paulo, SP, BrasilAl of them evaluated at least 10 papers in 2016 and took 2 to 6 days to perform the revision. This effort and the agility of the Associated Editors allowed a median time of 54.2 days from submission to final decision for publishing, with an acceptance rate of 27.1%.With the update of the journal website (www.intbrazjurol.com.br) and the policy of fast publication on line (Ahead of Print) of the accepted papers, today it is possible to have a paper published at International Brazilian Journal of Urology and consequently at Medline in a median time of 90 days after submission.Another novelty of the website (very important to Brazilian authors and urologists) is the possibility to access on line all editions in full of the old Jornal Brasileiro de Urologia, since number 1, 1974.The International Brazilian Journal of Urology is totally costed and supported by Brazilian Society of Urology and all publishing production is made by regularly employed officials at the Society headquarters. The joint effort of Ricardo de Morais, Technical Editor, Bruno Nogueira, Production Editor and Patricia Gomes, Secretary, has made our Journal more interactive and more competitive over the years.Professor Titular Disciplina de Urologia da Faculdade de Medicina do ABC, Santo André, SP, BrasilSidney Glina, MD, PhD


Clinical and Experimental Emergency Medicine among the list of so-called “predator” journals. Clinical and Experimental Emergency Medicine (CEEM) is non-for-profit, peer reviewed and the official English language journal of the Korean Society of Emergency Medicine inaugurated about two year ago. The journal does not charge publication fees and is funded by the Korean Society. The journal has just been included into PubMed. The Korean Society of Emergency Medicine represents hundreds of Korean emergency physicians and is a highly reputable organization. Korean emergency physicians have made significant contributions to the body of emergency medicine and acute care knowledge, some of which have been published in CEEM as well as many other well-established journals. The editorial board of CEEM includes multiple internationally renowned emergency physicians who have joined forces to support the efforts of the Korean Society. CEEM was established as a platform for a large number of Asian emergency physicians to highlight many of the issues unique to this region. In today’s era of emergency medicine globalization and rapid international growth it is important for all of us to come together and support the efforts of national emergency medicine organizations to grow their clinical and academic missions, such as the establishment of new journals like CEEM. Thus, extreme care should be taken before prematurely labeling young yet perfectly legitimate journals as “predators,” especially in our relatively young field of emergency medicine.I read the article by Hansoti et al. with great interest in which they list “predatory” open access emergency medicine journals. Dear Dr. Singer,WestJEM five years and three attempts with major improvement prior to acceptance to MEDLINE.We greatly appreciate your interest and comment on our study.Clinical and Experimental Emergency Medicine (CEEM) was not found in any of the selected directories, indexes, databases, and publishers that we searched at the time the study was conducted. We are happy to discover that CEEM is now listed in the National Library of Medicine (NLM) Catalog. The detail record  shows CEEM content is now archived and accessible in PubMed Central (PMC) . As a result, its abstracts are automatically migrated to PubMed as well. This is an important milestone for CEEM to be recognized by NLM and we congratulate the Editorial Board for a major accomplishment.While the methodology we chose to use in our study was imperfect, we did address several limitations. Our intention was to present the likely predatory vs. legitimate OA journal titles and their website links as aids to authors to further scrutinize the journal before submission. As indicated, CEEM website . It is well designed, clear, and meets all the criteria for a legitimate, official journal website. Its information includes the 12 questions that our study posted for readers and researchers to be considered when reviewing a journal or publisher’s website. Interestingly, CEEM is a unique OA journal that does not charge authors any processing fee. “There is no author’s submission fee or other publication-related fee since all costs of the publication process are underwritten by the Korean Society of Emergency Medicine .”We also did a thorough review of the current Your letter and another inquiry led us to check and update the information included in the original Again, thank you for bringing this oversight to our attention. In the spirit of open access, we encourage other legitimate scientists and publishers to expand the space for emergency medicine scholarship, so research and best practice can be freely available to the developed and developing world.Sincerely,Linda S. Murphy, MLIS, Research Librarian for the Health Sciences, University of California, Irvine LibrariesBhakti Hansoti, MBChB, MPH, Johns Hopkins University, Department of Emergency Medicine, Baltimore, MarylandMark I. Langdorf, MD, MHPE, University of California, Irvine, Department of Emergency Medicine, Irvine, California


The frontal eye fields (FEFs) are one likely source of iSC preparatory activity, since FEF preparatory activity is also inversely related to SRT. To better understand the FEF’s role in saccade preparation, and the way in which such preparation relates to SRT, in two male rhesus monkeys, we compared iSC preparatory activity across unilateral reversible cryogenic inactivation of the FEF. FEF inactivation increased contralesional SRTs, and lowered ipsilesional iSC preparatory activity. FEF inactivation also reduced rostral iSC activity during the gap period. Importantly, the distributions of SRTs generated with or without FEF inactivation overlapped, enabling us to conduct a novel population-level analyses examining iSC preparatory activity just before generation of SRT-matched saccades. When matched for SRTs, we observed no change during FEF inactivation in the relationship between iSC preparatory activity and SRT-matched saccades across a range of SRTs, even for the occasional express saccade. Thus, while our results emphasize that the FEF has an overall excitatory influence on preparatory activity in the iSC, the communication between the iSC and downstream oculomotor brainstem is unaltered for SRT-matched saccades.A neural correlate for saccadic reaction times (SRTs) in the gap saccade task is the level of low-frequency activity in the intermediate layers of the superior colliculus (iSC) just before visual target onset: greater levels of such  How does the brain decide when to move? Here, we investigate the role of two oculomotor structures, the superior colliculus (SC) and frontal eye fields (FEFs), in dictating visually-guided saccadic reaction times (SRTs). In both structures, higher levels of pretarget preparatory activity precede shorter SRTs. Here, we show that FEF inactivation increases SRTs and decreases SC preparatory activity. Surprisingly, providing one examines SRT-matched saccades, a population-level analysis of SC preparatory activity showed a negligible impact of FEF inactivation. Thus, while the FEF is one important source of preparatory input to the SC, it does not alter the dynamics of how iSC preparatory activity relates to a given SRT.The time to respond to a behavioral event can be highly variable. Even for simple tasks requiring saccades toward suddenly appearing visual targets, saccadic reaction times (SRTs) range from those approaching the minimal sensory-to-motor delays in the case of express saccades to others that are two to three times longer . One neuThe goal of the current study is to investigate how inactivation of the frontal eye fields (FEFs) alters the relationship between iSC preparatory activity and SRT while monkeys generate visually-guided saccades in a gap-saccade task. The FEFs are a source of top-down information to the iSC , and FEFOur choice of a gap saccade task is advantageous: although the changes in saccadic behavior are less than those observed for delayed saccades , the disMacaca mulatta, DZ, and OZ weighing 9.8 and 8.6 kg, respectively) were prepared for head immobilization, cryogenic inactivation of FEF and electrophysiological recordings from the iSC. All training, surgical, and experimental procedures were in accordance with the national Council on Animal Care policy on the use of laboratory animals  were administered pre- and postoperatively, and anti-inflammatories (metacam) and analgesics (buprenorphine) were administered postoperatively. In addition, dexamethasone was administered postoperatively to minimize the potential of brain swelling following the insertion of the cryoloops.The goal of the first surgery was to prepare the animal for head-immobilized measurements of eye movements, and extracellular recording within the iSC. A head holder and a recording chamber were embedded in an acrylic implant, with the recording chamber positioned over a 19-mm craniotomy that permitted a surface normal approach to the iSC. During the experiments, a grid was placed within the recording chamber to standardize our exploration of the iSC. Following recovery of more than one week, the animals were trained on a variety of oculomotor tasks.2 craniotomy at the stereotaxic coordinates of the arcuate sulcus spur to allow for insertion of both IA and SA cryoloops. In this study, we have only used unilateral IA cooling in both monkeys as this increases trial yield during cooling and produces ∼70% of the SRT deficits caused by combined unilateral cooling of the IA and SA , superior arm (SA)]. We customized the cryoloops based on an anatomic magnetic resonance image (MRI) obtained from each monkey, implanting in each case a ∼3 × 7 and ∼3 × 5 mm (depth × length) cryoloop in the IA and SA, respectively. We performed a small 2.25-cmA and SA .Monkeys were seated in a custom-made primate chair with their head immobilized and faced a rectilinear grid of >500 red LEDs covering ±35° of the horizontal and vertical visual field. The visual angle subtended by the LEDs was 0.36°. The eye movements were recorded using a single, chair-mounted eye tracker . All experiments were conducted in a dark, sound-attenuated room. The behavioral tasks were controlled by customized real-time LabView programs on a PXI controller  at a rate of 1 kHz. Extracellular single-unit activity was recorded with epoxylite insulated tungsten microelectrodes  lowered through 23-gauge guide tubes and advanced to the dorsal surface of the SC using a microdrive (NAN Instruments). Neural activity was amplified, filtered, and stored for off-line sorting via a Plexon MAP system (Plexon).FEFwarm condition. Data collected during FEF inactivation was termed as coming from the FEFcool condition. Importantly, qualitatively similar results to those presented in the Results section were obtained when we compared FEFcool with data collected from either the pre- or post-cooling condition alone . Thus, pooling data across pre- and post-cooling session did not alter the main conclusions drawn from the data.An experimental dataset consisted of pre-cooling, peri-cooling, and post-cooling sessions, with each session containing 60–120 correct trials . After the pre-cooling session, the cooling pumps were turned on allowing the flow of chilled methanol through the lumen of the cryoloops. The peri-cooling session was initiated when cryoloop temperature reached and stayed stable at 3°C. Once sufficient data were collected for the peri-cooling session, cooling pumps were turned off, which allowed the cryoloop temperature to rapidly return toward body temperature. When cryoloop temperature exceeded 35°C, the post-cooling session was initiated. It took 30–40 min to collect a full experimental dataset for a recorded neuron including the transition periods from pre-cooling to peri-cooling and from peri-cooling to post-cooling (which took ∼3 min). To control for time dependent factors like satiation and to help increase statistical power, we pooled data from pre-cooling and post-cooling session and termed this the Monkeys performed intermixed visually-guided gap and no-gap saccades to peripheral targets placed either in the center of the neuron's response field (RF) or in the diametrically opposite location. As this study concerns saccade preparatory activity in caudal iSC and fixation activity in rostral iSC, we only present data from the gap saccade task. Monkeys fixated the central fixation LED for 750–1000 ms until it disappeared. On gap trials, after a blank period of 200 ms , during which the monkeys maintained central fixation, a peripheral target appeared for 150 ms to which the monkeys had to saccade as quickly as possible. No-gap trials were the same but without a 200-ms gap interval, i.e., fixation LED disappearance coincided with peripheral target’s appearance. Saccades made within 500 ms after peripheral target appearance within a circular spatial window  received fluid reward. The large tolerance window was based on the expected spatial deficits that follow FEF inactivation . HoweverA recent study suggested that low frequency activity in the caudal iSC during a delayed saccade task may carry additional information about saccade kinematics in addition to preparatory signals . An impoAll behavioral analyses were conducted using customized MATLAB programs . Eye position traces were filtered using a 3rd order low pass butterworth filter and differentiated to produce eye velocity. Eye velocity was used to determine the onset and offset times of saccades with a velocity criterion of 30°/s and the maximum instantaneous velocity between saccade onset and offset was deemed as peak velocity. The eye position at saccade offset was used to calculate the mean saccade amplitude  and end-point scatter which represented the mean angular distance between the displacements of mean and individual saccade end points from the central fixation position . We analp < 0.05; Wilcoxon sign rank test; pooled across both target directions).We estimated the instantaneous firing rate of a recorded neuron with a continuous spike density function for each trial, generated by convolving the spike train with a postsynaptic activation function with a rise time of 1 ms and a decay time of 20 ms . Use of We also recorded neural activity from the rostral iSC. There are differences in opinion regarding the role of the rostral iSC in visual fixation . Previour), y-intercept and slope of this relationship across FEF inactivation. A linear regression between PREP and SRT yielded qualitatively similar results. For the rostral iSC fixation neurons, a trial by trial linear regression between either final PREP or PREP with SRT did not yield significant correlations.We performed trial-by-trial linear regression (Pearson’s correlation) between final PREP and contralateral SRT in buildup neurons and compared the correlation coefficient  of either behavior or single neuron activity were performed using a Wilcoxon rank sum test at a p value level of 0.05. For buildup neurons, we compared activity during the baseline, PREP, and final PREP intervals, and also calculated the onset time of PREP accumulation. We also compared the slope of PREP, which was calculated by differentiating the spiking activity in the PREP interval. For the rostral iSC, slope and onset times of the PREP activity was compared over the same time epochs. To assess changes in SRT and neural activity across the sample of recorded iSC neurons following FEF inactivation, we performed paired group level comparisons using a Wilcoxon sign rank test at a p level of 0.05. We also implemented a novel population-based analysis comparing population PREP activity for SRT matched saccades across FEF inactivation. The logic and description of this analysis is described in Results.In this study, we compare both behavior  and neuronal activity across FEF inactivation. Single session comparisons (FEFWe report single unit activity from the left iSC of two monkeys (DZ and OZ) while the left FEF was reversibly inactivated by cryogenic means, when animals were engaged in the gap saccade task. Cryogenic inactivation was restricted to the cryoloop in the IA of the arcuate sulcus. Previous work of ours  investign = 89 sessions), 48 caudal iSC saccade-related neurons (27 from monkey DZ and 21 from monkey OZ) could be isolated for long enough to collect sufficient pre-, peri-, and post-cooling data. Of these 48 neurons, 35 exhibited significant preparatory activity (PREP), and were classified as buildup neurons . RFs centers for the buildup neurons ranged between 4°/6° and 20°/20° in horizontal/vertical coordinates relative to fixation point with the mean response center of 9 ± 3.7°  and 2.5 ± 5.8° . Fixation-related activity was also recorded from 17 rostral iSC neurons .We performed 54 inactivation sessions in monkey DZ and 35 inactivation sessions in monkey OZ. In each session for a neuron to be further analyzed, between 15 and 30 valid trials per target location in each of the pre-, peri- and post-cooling sessions were deemed necessary. Across all the inactivation sessions . In contrast to previous reports, such inactivation did not consistently increase ipsiversive SRTs . The failure to observe ipsiversive SRT increases may be due to differences in target configuration and behavioral task . Vertical saccade amplitude showed a significant, albeit small, decrease . The mean endpoint scatter of saccades did not change in 59 out of 89 sessions  and across all sessions also showed only a small but significant increase from 1.04 ± 0.30° to 1.27 ± 0.34° . Next, we compared peak saccade velocity across sessions and found a reduction in peak saccade velocity in 63 out of 89 sessions during FEF inactivation . Across sessions, mean saccade peak velocity decreased significantly . We also compared fixation offsets across sessions and found a small but significant shift in horizontal eye position toward the side of FEF inactivation . Further, only monkey Dz exhibited a significant vertical upward shift in eye position . In 55 out of 89 sessions and 29 out of 89 sessions, we observed significant horizontal and vertical offsets of eye positions during fixation . Although we observed significant changes in fixation position during FEF inactivation, such changes were quite small, and trial-by-trial fixation positions overlapped considerably in the FEF warm versus cool condition, similar to that reported previously in another study .We next investigated how the increase in SRT during FEF inactivation related to changes in iSC preparatory (PREP) activity. Such activity precedes the arrival of visual information into the iSC, and hence is driven strictly by top-down factors such as the expectation of target appearance and/or bottom-up factors like fixation disengagement due to the 200-ms gap . Figure warm condition to 47 spikes/s and 94 spikes/s during the FEFcool condition, respectively . The slope of the accumulation of PREP also decreased significantly for these neurons  although baseline activity did not change . In contrast, for the neuron shown in p = 0.27, z-val = −1.1005), PREP activity , final PREP , or slope of accumulation of PREP  changed significantly during FEF inactivation (Wilcoxon rank sum test) despite a significant increase in contraversive SRT during this session . Across our sample of 35 neurons, at the single neuron level, 11 (25%), 14 (40%), 14 (40%), and 6 (17%) neurons exhibited significant decreases in baseline, PREP, final PREP, and slope of PREP, respectively .For the neurons shown in p = 0.12, z-val = 1.5724; Wilcoxon sign rank test), but lowered overall PREP activity , the rate of accumulation of PREP activity  and the final PREP attained just before the arrival of visual information . Thus, FEF inactivation produced a widespread decrease in PREP activity in the caudal iSC.Next, we analyzed the changes in PREP activity in caudal iSC neurons at the group level. Across our sample of 35 neurons, FEF inactivation did not significantly alter baseline activity .A recent study showed that cyrogenic FEF inactivation delayed the onset of saccadic activity in a delayed saccade task . We wondOne theory regarding intracollicular communication states that the rostral and caudal portions of the iSC are mutually antagonistic . Given tp = 0.01, z-val = 2.4379; Wilcoxon sign rank test), and PREP activity . However, the rate of accumulation of PREP activity  and the final PREP attained just before the arrival of visual information  were not changed due to FEF inactivation.Next, we analyzed the changes in rostral iSC neurons at the group level. Across our sample of 17 neurons, FEF inactivation significantly altered baseline (p = 0.05), the decrease in fixation-related activity during FEF inactivation persisted during both baseline  and PREP epochs  epochs. Thus, in contrast to what would have been expected based on a reciprocal inhibitory relationship between the caudal and rostral iSC, FEF inactivation reduced, rather than increased, fixation-related activity in the rostral iSC.One caveat of the above analysis is that rostral iSC neurons are sensitive to stimulus location  relative to instantaneous eye position . Could tp = 0.62; z-val = 1.3416; Wilcoxon sign rank test).We also analyzed the onset of the decrease in fixation-related activity during the gap interval across FEF inactivation. Like the result obtained for PREP activity, we found no change in the onset time of PREP activity across our sample of neurons relative to the offset of the fixation point , similar to previously published results.Consistent with previous studies , before How then did the relationship between PREP activity and the subsequent SRT change during FEF inactivation, considering the overall reduction in the level of PREP activity? We were particularly interested in how many neurons retained a significant PREP-SRT relationship, whether there was any change in the amount of SRT variance explained by PREP variance, and whether there were any changes in the parameters of a linear fit through the PREP-SRT relationship .Surprisingly, FEF inactivation produced a diversity of effects on the PREP-SRT relationship, with the relationship either remaining B, or disr value) of the PREP-SRT correlation did not differ across the FEF warm versus cool conditions, regardless of whether we considered all 35 neurons , or only the subset of neurons exhibiting a significant PREP-SRT correlation on an individual neuron basis in both FEFwarm and FEFcool condition . For the 11 neurons that exhibited a significant correlation in both the FEF warm and FEF cool conditions, we found significant increases in both the y-intercept  and a steepening of the slope . Effectively, these changes mean that the linear regressions were pivoting around the lower SRT ranges, so that progressively greater levels of PREP activity preceded longer-SRT saccades . We then identified a 50-ms range where the SRT distribution in the FEFwarm and FEF cool conditions overlapped, with at least 5% of the total trials within each 10-ms bin. The range of overlapping SRTs was 110–160 ms for monkey DZ .The population spike density functions arising from this analysis are shown in In summary, this population level analysis revealed that the overall level of iSC preparatory activity was unaltered during FEF inactivation, providing one compares saccades matched for SRT.p = 0.59; z-val = -0.5287; Wilcoxon sign rank test). However, the level of baseline was significantly increased during FEF inactivation  and the slope of PREP accumulation increased  anterior to arcuate sulcus, which is where the FEF is located. Given this, and the saccadic deficits observed during delay- and memory-guided saccade tasks for the same animals  in others. This finding resembles similar reports of a diversity of effects of FEF inactivation on saccade-related activity . We haveDespite differences in the effects of FEF inactivation on single neurons, we found that the level of iSC preparatory activity across the population was unaltered during FEF inactivation, providing one compares SRT-matched saccades. Our interpretation is that while FEF is one important source of top-down excitatory input to iSC, it is not the sole source. Presumably, when inputs from other cortical areas like the DLPFC, SEF, and LIP  and subcOur observation of an unaltered population profile for preparatory signals also extends to express saccades. Behavioral  and neurOur results permit some speculation on the functional physiology of FEF projections that bypass the iSC and directly contact the oculomotor brainstem. This bypass pathway, which was shown by anatomic studies , is thouWe have shown that FEF inactivation reduces iSC preparatory activity and increases SRT. However, the level of iSC preparatory activity associated with a particular SRT is unchanged during FEF inactivation. This observation is inconsistent with a role for the FEF in saccade triggering in the context of our task; had this been then case, then one would have expected increased iSC preparatory activity for a given SRT, to compensate for the loss of signaling from the FEF. Instead, providing that other inputs can get the iSC to a particular level of activity, a saccade of a given SRT will be generated. Thus, signals relayed via the bypass pathway would appear to have a negligible role in integration of visual and preparatory signals into a saccade triggering signal, as the dynamics by which SC and brainstem circuits trigger a saccade appears to be preserved during FEF inactivation in this task.


For skin defects caused by full-thickness burns, trauma, or tumor tissue excision, skin grafting is one of the most convenient and useful treatment methods. In this situation, graft fixation is important in skin grafting. This study was performed to compare the effectiveness of skin graft fixation between high-concentration fibrin sealant and sutures. There have been numerous studies using fibrin sealant for graft fixation, but they utilized slow-clotting fibrin sealant containing less than 10 IU/mL thrombin.Twenty-five patients underwent split-thickness skin grafting using fast-clotting fibrin sealant containing 400 IU/mL thrombin, while 30 patients underwent grafting using sutures. Rates of hematoma/seroma formation, graft dislocation, graft necrosis, and graft take were investigated postoperatively. The graft surface area was calculated using Image J software .p < 0.05) except graft dislocation.After 5 days, rates of hematoma/seroma formation and graft dislocation were 7.84 and 1.29% in group I, and 9.55 and 1.45% in group II, respectively. After 30 days, rates of graft necrosis and graft take were 1.86 and 98.14% in group I, and 4.65 and 95.35% in group II. Undiluted fibrin sealant showed significantly superior results for all rates (When high-concentration fast-clotting fibrin sealant was applied to skin grafts without dilution, no difficulty was experienced during surgery. Sealant showed superior results compared with sutures and had an excellent graft take rate.II. Skin grafting is one of the most convenient and useful treatment methods for skin defects caused by full-thickness burns, trauma, or tumor tissue excision. In skin grafting, graft fixation is important. Use of sutures or staples is a standard method for skin fixation .Undiluted fast-clotting fibrin glue was used for graft fixation in 25 patients (group I). Greenplast —a fast-clotting fibrin sealant containing 400 IU/mL thrombin—was used in this study. During surgery, a marginal incision was made in the skin defect area, and an even layer of fibrin sealant was sprayed on the healthy wound. The skin graft was applied on the sealant layer, and fibrin sealant was applied once more to the graft boundary. Sutures and metallic staples were not used. Moderate compressive dressing was performed using mesh gauze and a gauze bandage Figs. , 2, 3.FiThe classic graft fixation method using silk sutures or staples was performed in another 30 patients (group II). Fibrin glue was not used in this group Fig. . ModeratThe dressing in the graft area was changed for the first time 5 days postoperatively, and hematoma/seroma formation and surface area of graft dislocation were investigated. At 30 days postoperatively, graft necrosis and graft take were investigated. Ratios of total surface area to hematoma/seroma formation, graft dislocation, graft necrosis, and graft take were obtained using Image J software .t test and Pearson correlation coefficients. A value of p < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS version 13.0 software .Statistical analysis was done using the independent 2 (the range 6–110 cm2) in group I versus 39.85 cm2 (the range 12–90 cm2) in group II. All subjects underwent split-thickness skin grafting, with a mean follow-up period of 16.4 months.The major mechanisms of trauma in the 55 subjects were pedestrian and bike accidents and contact burns. Among the 55 subjects, all wounds were located on upper and lower extremities where the skin was hard to fix. The size of the defect area ranged from 3 cm × 2 cm to 22 cm × 5 cm. The median area of skin graft was 35.5 cmp < 0.05) except graft dislocation and revealed superior outcomes compared with sutures except graft dislocation.After 5 days, rates of hematoma/seroma formation and graft dislocation were 7.84 and 1.29 in group I, and 9.55 and 1.45% in group II, respectively. After 30 days, rates of graft necrosis and graft take were 1.86 and 98.14% in group I, and 4.65 and 95.35% in group II (Table 2) and graft necrosis which means graft loss (cm2) as the previous study , while in group I this relation is also observed but showed the less stiffness of the slope .When analyzing the influence of the area of skin graft  could be more effective in large area grafting.2 has been reported to enhance the graft take rate (Mittermayr et al. Sealant application thickness is also important for successful graft take. When the fibrin sealant layer is excessively thick, nutrition supply and neovascularization for the host and graft may be inhibited. This problem can occur with both fast- and slow-clotting fibrin sealants (Mittermayr et al. Use of fibrin sealant would be advantageous for patients if it could be obtained easily. Because fibrin sealant biodegrades within 2 weeks, foreign bodies, such as sutures and staples, are not left in the wound, especially in the granulation bed. In addition, patients often report severe pain when staples are removed, and occasionally, an anesthetic procedure is required (O’Grady et al. As described previously, use of fibrin sealant can overcome the disadvantages associated with sutures and staples. Fibrin sealant has been used for skin graft fixation since 2000, and comparative studies on the thickness of the sealant layer have been reported (Mittermayr et al. Although fibrin sealant has proved useful for skin graft fixation and graft take, it is not widely used compared with sutures or skin staples. When high-concentration fast-clotting fibrin sealant containing a thrombin concentration of 400 IU/mL was applied to skin grafts without dilution, no difficulty was experienced during surgery. Sealant showed superior results compared with sutures, and had an excellent graft take rate.


In this study, starch and polycaprolactone (PCL), composite nanofibers were fabricated by co-axial needle electrospinning technique. Processing parameters such as polymer concentration, flow rate and voltage had a marked influence on the composite fiber diameter. Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), mechanical and physical properties  of the composite fibres were evaluated. Moreover, a cell culture test was performed in order to determine their cytotoxicity for wound dressing application.The effect of starch ratio in the solution on the properties and morphological structure of the fibers produced was presented. With lower starch concentration values, the fibers have greater ultimate tensile strength characteristic (mostly 4 and 5 wt%). According to SEM results, it can be figured out that the nanofibers fabricated have good spinnability and morphology. The mean diameter of the fibers is about 150 nm. According to results of cell culture study, the finding can be determined that the increase of starch in the fiber also increases the cell viability.Composite nanofibers of starch/PCL have been prepared using a co-axial needle electrospinning technique. PCL was successfully encapsulated within starch. Fiber formation was observed for different ratio of starch. With several test, analysis and measurement performed, some important parameters such as quality and effectuality of each fiber obtained for wound dressing applications were discussed in detail. Nanotechnology is a newly-emerging and up-to-date technology that has been classified as a vital scientific and commercial venture with economic benefits in global scale. By rapid development of technology in last decades, the knowledge on nanomaterial manufacturing techniques have been increased and this consequently promoted, research groups studying on several areas around the world, to focus more on the preparation or syntheses techniques of nanomaterials for a variety of applications. According to literature, it can easily be seen that various techniques are reported for the fabrication of nanomaterials for different purposes. These techniques include drawing-processing, template-assisted synthesis, self-assembly, solvent casting, phase separation, and electrospinning techniques –3. AmongElectrospun nonwoven provide high-surface area, micro/nano-porosity, and the ability to add drugs, polymers or biomolecules into the nanofibers . There mIn this study, the preferred method is co-axial needle electrospinning and the aim is to use the final products, which are nanofibers, in biomedical applications such as wound dressing.Open wounds have high tendency to infection and bacterial colonization. Therefore, the property of bacterial barrier is an important parameter that can specify the success of a wound covering material . BarrierAccording to research made in biomedical applications, it has been indicated that synthetic or natural agents can be successfully used in wound dressing applications. Both synthetic polymers and natural polymers include in their structure hydrolytically or enzymatically labile bonds or groups are degradable . The advStarch is the centre of attention among lots of natural polymers. It is obtained from carbon dioxide and water by photosynthesis in plants . By meanIn this work, starch/PCL composite nanofibers were fabricated with the electrospinning technique. Several characterization tests such as density, viscosity, electrical conductivity were performed. In order to report the structure characterization and morphology analysis of nanofibers produced, Fourier transform infrared (FTIR) and scanning electron microscope (SEM) analysis were conducted, respectively. Furthermore, cell culture testing was carried out to be able to demonstrate that nanofibers fabricated have great potential for wound dressing application.6H10O5)n, average molecular weight Mw ~106 g mol−1, amylose:amylopectin 25–28:72–75%} and dimethyl foramide (DMF) were supplied by Sigma Aldrich, UK. Dimethyl sulfoxide (DMSO) which is colorless and clear liquid {(CH3)2SO}, average molar mass 78.1 and its storage conditions at between +15 °C and +30 °C) was supplied by Merck KGaA. The average molecular weight of PCL (Mw) is 80,000 g mol−1, which was purchased from Sigma-Aldrich and used with no extra treatment or purification.Starch derived from corn { was dissolved in DMSO by stirring and heating at the same time and cooled down to room temperature whereas PCL (10 wt%) was dissolved in DMF and the same procedure was performed for this solution. Since different solvents were used it is not possible to mix them and electrospin. Instead, different needle was utilized for each solution which is called as co-axial electrospinning process.The experimental set up used in this study is demonstrated in Fig. −1). At selected flow rates, from 25 kV up to 30 kV voltage was applied.All experiments were performed at the ambient temperature. Processing a physically mixed composite solution was carried out by infusing the material into both the needles. The flow rates of these were fixed at a ratio of 1:2 for inner and outer needles, respectively. For encapsulation co-axial experiments, PCL solution was fed through the inner needle at half the flow rate of the starch solution. This solution was fed through the outer needle at various flow rates . Electrical conductivity was assessed using a conductivity meter whose model is Cond 3110 SET 1 . All measurements were performed at the ambient temperature.−1 in transmission mode.FT-IR analysis was used to qualitatively characterize the functional groups of the electrospun fibers. The infrared (IR) spectra of starch/PCL composite samples were recorded on a Thermo Nicolet 6700 FTIR spectrophotometer equipped with Smart Orbit diamond ATR accessories. Measurements were conducted at room temperature between 400 and 4000 cmThe morphological characterization of the starch/PCL composite nanofibers was examined using a scanning electron microscope . The pores, bead structures and nanofibers were observed and diameter range of fibers was determined on SmartSEM, which is the graphical user interface of the device. The samples were put on a metal stub using carbon adhesive tape and coated with gold under vacuum before observation.−1 and room temperature of (23 °C) were prepared. The cross-section is rectangular dimensions of 1 × 5 cm and the same for all test samples [Ultimate tensile strength (UTS) and elongation values were performed and measured by Instron 4411 tensile test machine by means of running a special software . The test speed of 5 mm min samples . Three d2. The culture medium was changed every second day. Cell viability was measured MTT assay according to manufacturer’s protocol (Sigma USA). Firstly all samples were sterilized with 70% ethanol and UV then small piece of membranes were laid down onto 96 well plate and cells were plated onto samples surface 103 cells per well in 96 well plate. Control was just tissue culture plate surface. After 1 and 3 days later 20 µl MTT solution (5 mg ml−1) was added into each well. After additional incubation for 4 h, 100 µl DMSO was added. The absorbance was read at 595 nm wavelength with microplate reader. Experiments were performed in triplicates. A test was performed to determine the statistical significance between experimental groups. Kruskal–Wallis test was used to compare the groups. A value of p < 0.05 was considered to be statistically significant.NIH-3T3 mouse fibroblast cell lines were used and cultured in DMEM with 10% FBS at 37 °C, 5% COThe effect of starch concentration on the physical characteristics which are density, electrical conductivity and viscosity of starch solution was obtained and results are shown in the Table −1, respectively. While the bands at 1144 and 1066 cm−1 depend on the ordered structures of starch, the band at 995 cm−1 represents the starch that is amorphously structured [−1 of starch were imputed to the bending vibration and stretching vibration of C–O, respectively. Moreover, the wide absorption band around 3423 cm−1 was because of the stretching vibration of O–H [Figure ructured . The chan of O–H .Fig. 2a−1 (asymmetric CH2 stretching), 2865 cm−1 (symmetric CH2 stretching), 1727 cm−1 (carbonyl stretching), 1293 cm−1 (C\O and C\C stretching), 1240 cm−1 (asymmetric C\O\C stretching) and 1170 cm−1 (symmetric C\O\C stretching) [Several characteristic bands of PCL were observed at 2949 cmetching) .Morphological study has an importance to visualize and understand the orientation of structures inside the nanofibers fabricated. SEM image was used to observe the morphology of the starch/PCL composite nanofibers and it is shown in the Fig. In this Fig. In order to perform tensile testing, the prepared nanofiber samples with different concentration of starch were used. While comparing the results to each other, the changing parameter was the concentration of starch which are 4, 5, 6, 7, 8 and 10 wt%, respectively. The mean value of Young’s modulus and strain at break were determined and listed in the Table According to these results, it can be deduced that the Young’s modulus values are relatively higher for lower concentration values, such as 4 and 5 wt%, of starch in fibers Table . OptimumUltimate tensile stress is another important factor to determine material characteristics of nanofibers produced. It represents the highest stress value at which nanofiber could hold without breaking. Ultimate tensile stress values for each sample are given in the Fig. Based on the analysis of ultimate tensile stress, it can be easily concluded that nanofibers’ ultimate tensile stress values somehow have a tendency to decrease with the increase of starch concentration. This shows that how the concentration of secondary materials affects the ultimate tensile stress of composite nanofibers produced. It depends on the properties of material added. Different type of materials and concentration values can give different results .In order to carry out cell culture study, the composite nanofibers of 4 and 5 wt% starch were used. It was observed that the materials have no cytotoxic effect on fibroblast cells. The materials have increased the reproduction of cells since the first day. The material with the concentration of 5% increased the cell growth more than the one with the concentration of 4%. At the end of the third day, approximately, the material with the concentration of 4% increased the cell growth at the rate of 30% so did the one with concentration of 5% at the rate of 40%. The results are shown in Fig. According to results of cell culture study, the finding can be determined that the increase of starch in the fiber also increases the cell viability. However, the further analysis and longer time range are needed to demonstrate this finding more properly. To compare the result to the similar ones reported previously, addition of starch increases the cell growth more than pure PCL usage. Oh et al.  showed tComposite nanofibers of starch/PCL have been prepared using a co-axial needle electrospinning technique. PCL was successfully encapsulated within starch. Fiber formation could have been observed for different ratio of starch. The effect of starch ratio in the solution on the properties and morphological structure of the fibers produced was presented. With lower starch concentration values, the fibers have greater ultimate tensile strength characteristic (mostly 4 and 5 wt%). According to SEM results, it can be figured out that the nanofibers fabricated have good spinnability and morphology. The mean diameter of the fibers is about 150 nm. According to results of cell culture study, the finding can be determined that the increase of starch in the fiber also increases the cell viability. However, such further analysis may be required to demonstrate this characteristic. Several characterization analysis have been performed and based on this, it was demonstrated that the starch/PCL composite nanofibers have great potential for wound dressing applications.


At the request of the authors and the hospital, the article titled “The Impact of Graft Nephrectomy on Subsequent Transplants: Multivariate Analysis of Risk Factors for Second Graft Loss and for Multiple Transplantations–A Single-Center Retrospective Study”  has been


Dear Colleagues,In this evolving world, when information is piling up from different corners, scientific journal represents one of the most important avenues of transmission of knowledge from the sources to the users. In fact, the need of scientific journals in developing countries is enormous, but very few are coming out from there. This is more relevant in the field of gastroenterology and hepatology. In one hand, the numbers of patients with gastroenterological and hepatological problems are on rising trend in these parts of world. On the contrary, many of these patients are not able to follow the treatment guideline provided by advanced and developed countries. These facts indicate that there should be ongoing investigations about epidemiology, pathogenesis, prevention and therapy of different diseases within the disciplines of gastroenterology and hepatology to optimize with the need of these patients at developing countries. The retrieved information should reach the hands of physicians policy makers, and medical associates of these regions.To my understanding, the ‘Euroasian Journal of Hepato-Gastroenterology’, that is endorsed by liver organizations of more than 10 countries, deserves a specific place among the journals of these disciplines. In most cases, a journal of a discipline is endorsed by usually one organization. The Euroasian Journal of Hepato-Gastroenterology is going to complete its 4 years of regular publication, a significant event for any journal of this region. Also, conferences and seminars of this area are well represented in this journal.Standing at the footstep of 5th year of its publication, I extend my congratulation to the contributors, editors and publishers of the journal. I am sure that the journal would soon be reflected as a prominent journal of this region.Yoichi Hiasa, MD PhDProfessorDepartment of Gastroenterology and MetabologyEhime University Graduate School of MedicineShitsukawa, Toon, Ehime 791-0295, Japan


Dear esteemed colleagues and friends,International Brazilian Journal of Urology. We are committed in publishing the highest quality videos detailing novel surgical techniques and approaches by leading surgical teams from across the world. Similarly, we encourage groups pushing the envelope in terms of how we can continually refine the art of surgery and ultimately improve the outcomes of our patients. In this regard, I am pleased to share with you this year’s selection for best videos of the year for 2016. Many individual criteria were taken into account in making this selection including novelty, superior quality in terms of video depiction and narration, and lastly vides that best depict re-defining surgical approaches to urological diseases. On that note, here are the selections:As we begin a new year, I would like to take this opportunity to thank each of you for your commitment in supporting our journal and expanding its readership. This past year has been truly exceptional in the quality of submissions we have received within the video section of the First Prize:Robotic ureteroureterostomy for treatment of a proximal ureteral stricture by Andrade HS et al. from the Glickman Urological and Kidney Institute, Cleveland Clinic  published in volume 42(5):1041-1042, September-October 2016 (available at: http://www.intbrazjurol.com.br/video-section/andrade_1041_1042)  published in volume 42:168-169,Third Prize:Retzus-sparing robotic-assisted laparoscopic radical prostatectomy: A step-by-step technique description of this first Brazilian experience by Tobias-Machado M et al. from the Departmento de Urologia, Faculdade de Medicina do ABC, Santo Andre, SP, Brazil and other centers of excellence in Sao Paulo, SP, Brazil published in volume 42(6):1250, November-December 2016 (available at: http://www.intbrazjurol.com.br/video-section/tobias-machado_1250_1250) . This suInternational Brazilian Journal of Urology. We are committed in publishing the very best original articles and videos from across the world and similarly will continue to do so in a very timely manner, with a rigorous peer review process by the very best subject leaders. Lastly, I send my very best wishes to you and your families for 2017.I would like to conclude this editorial by once again thanking each of you for the support of the Video Section Editor,International Brazilian of UrologyAssociate member, Department of GU OncologyMoffitt Cancer CenterAssociate Professor, Department of UrologyUniversity of South FloridaTampa, Florida, USAE-mail: philippe.spiess@moffitt.orgPhilippe E Spiess, M.D, MS, FACS, FRCS(C)


The correct funding information is as follows: "The research was funded by UK aid from the Department for International Development (DfID), as part of the SHARE (


Chinese Medicine —the official journal of the International Society for Chinese Medicine (‘the Society’) [The past decade has witnessed the rapidly growing influence of Chinese medicine around the world. Both basic and clinical research into Chinese medicine has continued flourishing and become more international, interdisciplinary and interactive than ever. It was such a good timing that ociety’) —celebratFirst of all, the Society is delighted to announce the inauguration of the new leadership of the Journal, including the new Editor-in-Chief Professor Yitao Wang, six new Associate Editors, an international editorial and senior advisory board, as well as a Macau-based Editorial office. The Society sincerely thanks the former editorial and advisory team for their past service and hard work that has shaped our journal into what it is now; without their vision, leadership and dedication, the journal would hardly have made such achievements. Now, the new team comprises both established and emerging scholars from across the globe and interacts with a large pool of young, active scientists—they have already started to contribute their expertise in the past few months. The new team, together with our publishing partner BMC, pledges to bring the Journal into a new era, enabling it to evolve while firmly upholding its long-standing mission and strengths.Next, the new editorial office would like to highlight three specific changes, among other ongoing renovations, which are crucial for the interest of our readers, authors and reviewers.We acknowledged that it is necessary to shorten the manuscript processing time, based on the data in the past 3 years. The speed of publication (and rejection) is important to both our authors and the Journal. We strive to persist in the founding vision of the Journal—‘publishing evidence-led, scientifically justified, and ethical research into Chinese medicine’.  Yet, chaWe aim to make decisions on manuscripts faster using several approaches, which we have already started since March 2017. First, we strengthen our editorial screening before peer-review, with the help from the new international editorial team, so as to save time for authors whose papers are not falling into the scope of our journal or significantly lack scientific soundness. Second, in addition to the existing reviewers who have long helped us, we create a larger pool of reviewers including both established scientists and emerging talents, based on a strong network and rigorous recommendation from our editorial and advisory boards. Third, we cancel the post-acceptance editorial process, based on the feedback from many past authors and our own analysis into the purpose of scientific publishing.Nature [Chinese Medicine will be a leading journal in processing efficiency in the near future. This should be achieved without sacrificing the quality of peer review and the publishing standards we hold on to. We will show zero tolerance to a manuscript with ethical or research integrity-related issues.We are committed to shortening the waiting period for authors, in spite of the generally long publication process in biomedical journals, according to a recent analysis published in Nature . We highWe are dedicated to collaborating with the authors in publishing good research. And it will be our collaborative efforts to maintain research integrity. First, we have recently established a two-step similarity detection system to check each new submission, to help authors avoid the use of excerpts or complete sentences from other sources. We believe that deliberate plagiarism is rare, but we found this year a couple of cases that the authors unintentionally wrote the paragraphs that they previously published in their own paper (‘self-plagiarism’). We are confident that our system is effective in helping the authors rectify such practices.Second, under the guidance of COPE and with the support from BMC, we continue to emphasise the importance of research ethics to our respected authors and reviewers. We help the authors in completing the Checklist, with an emphasis on the items relating to animal/human subjects. We request authors to submit approvals from human/animal ethics committees for any research conducted with human and/or animal subjects—no matter it is a hypothesis-driven comprehensive research, a survey, a laboratory study involving transgenic mice or a multi-centre clinical trial on patients. A Trial Registration Number should also appear in the abstract of the paper , which iThird, in response to authors’ feedback that we have received, the Society is now discussing how we can more actively and efficiently support researchers who are planning to submit their best research to the Journal. Existing and potential initiatives include covering the article-processing charge for authors who are in reasonably special circumstances, who are long-term reviewers for the Journal, or who have been involved in organising workshops for the Journal, etc.Communication between authors and editors is vital. Hearing no response from the editorial office for long may frustrate the authors; likewise, receiving a revised manuscript with no effective response to the editors’/reviewers’ comments can prevent the editors from making timely decisions. Hence, our new editorial office welcomes enquiries, suggestions and feedback from our authors and is committed to responding as fast as possible.Meanwhile, we fully understand that reviewers are always busy and highly appreciate the efforts from our past and present reviewers. To invite more experts from different corners of the world to contribute as reviewers, we are promoting the Journal in multiple ways and expanding the expert pool through connections. For example, we have recently established strategic collaborations with academic organisations both in the field of Chinese medicine and beyond the traditional scope—notably including the Phytochemical Society Europe and Phytochemical Society Asia. The Society has co-organised 2nd International Symposium on Phytochemicals in Medicine and Food  held in April 2017 in Fuzhou, China and 3rd International Conference on Natural Products Utilisation: from Plant to Pharmacy Shelf (ICNPU 2017) recently held in Bulgaria. Moreover, the Society is preparing for 3rd International Symposium on Phytochemicals in Medicine and Food (3-ISPMF) to be held in Aug 2018 in Kunming, China. The Journal served as the designated platform to publish the proceedings. We have also organised two rounds of publishing workshop in Macau, having invited chief or associate editors of over 10 sister-journals in the area of pharmaceutical sciences to enhance collaboration in publishing, reviewing and resource-sharing. Additionally, through the strong network of our editorial/advisory board members, we have welcomed increasing numbers of early-career scientists to join our reviewer’s pool and planned to hold a young scientists referee meeting soon. We also prepare to invite the most outstanding ones from them to replenish our editorial board on a regular basis. All these initiatives aim to strengthen the connection between our editorial office and the authors and reviewers of the Journal, which will further benefit the development and promote the reputation of the Journal.In addition to the above three aspects, much work remains to be done in the coming year. To reiterate, we strive to work hard and smart to advance the Journal to the next stage, while upholding its long-standing mission and commitment to the global academic community. We plan to refine/redefine the scope of the Journal in 1 year, during which we will carefully identify our position in the fields, so as to better serve the authors in different specialities. We understand the importance of Impact Factor to research communities we serve. At the same time we will work with the journal publisher to present more metrics for measuring the impact of the research we publish. Journal gained a 2016 Impact Factor (IF) of 1.508; in the same year, it published 49 research and review articles. We are confident to see the IF increase because of all the efforts mentioned above and the level of commitment from the Editorial Board. Also, we will deepen our collaboration with both our publisher BMC and the organisations across different fields to raise the visibility of the Journal in both academia and the general public. Finally, we would love to welcome suggestions and feedback; we look forward to communicating with you—which is also the principal aim of this editorial article.


With the Fall 2000 issue of the JACMP, Volume 1 is complete, and a few observations are in order.From a modest start with four papers per issue the increase in the manuscript submission rate is such that we have been able to increase that number for this issue. If the submission rate continues to increase we will propose going to a bi‐monthly publication sometime in the near future.There have been about 8,500 visits to the journal Web site from approximately 650 unique hosts each month with an average of 650 manuscript downloads monthly. We also know that we are reaching an international readership including Australia, Canada, China, France, Korea, etc. and we have published papers from Canada and Taiwan in addition to the USA.Although this is an excellent start for a new journal I believe we can do better. Most of the manuscripts we receive deal with radiation oncology clinical physics. I would strongly encourage physicists working in other clinical areas such as imaging, health physics, machine maintenance and administration to submit manuscripts. I would also encourage our international readers to fully utilize the journal. We are pleased to receive manuscripts from clinical physicists worldwide.I am very pleased to announce that three of the ACMP's Corporate Members have underwritten annual awards for the best papers published in the JACMP during the previous calendar year. They are: “The Elekta Award for Excellence” for the best professional paper, generously underwritten by Elekta, Inc.; “The LAP Award for Excellence” for the best radiation oncology physics paper, generously underwritten by LAP of America Laser App. L.C.; and “The RIT Award for Excellence” for the best paper in diagnostic physics, generously underwritten by Radiological Imaging Technology, Inc. When you have the opportunity, take a moment to thank these Corporate Members for their ongoing support of the JACMP. The initial awards will be given at next year's annual meeting.I am also very pleased to announce that for the coming year (2001) the journal will remain subscription free. Access to and downloading of papers may be done without cost to the reader.The successful completion of the first year of publication of the JACMP would not have been possible without the hard work of many people, including the Associate Editors and the Editorial Board, all of the referees who take time to review the manuscripts, the Manuscript Manager who keeps the whole process running smoothly, the fine people at AIP and the corporations who advertise in the journal. My thanks to all of them.Peter R. Almond, Ph.D.Editor‐in‐Chief


The evolutionary adaptation of the influenza A virus (IAV) to human antibodies is well characterised. Much less is known about the long-term evolution of cytotoxic T lymphocyte (CTL) epitopes, which are important antigens for clearance of infection. We construct an antigenic map of IAVs of all human subtypes using a compendium of 142 confirmed CTL epitopes, and show that IAV evolved gradually in the period 1932–2015, with infrequent antigenic jumps in the H3N2 subtype. Intriguingly, the number of CTL epitopes per virus decreases with more than one epitope per three years in the H3N2 subtype (from 84 epitopes per virus in 1968 to 64 in 2015), mostly attributed to the loss of HLA-B epitopes. We confirm these observations with epitope predictions. Our findings indicate that selection pressures imposed by CTL immunity shape the long-term evolution of IAV. IAV persists by continuously escaping pre-existing immunity in the population. Most attention has been on the evolution of surface proteins hemagglutinin (HA) and neuraminidase (NA) that form the main targets of neutralising antibodies1245791113Viruses escape CTL recognition by mutating amino acid residues within CTL epitopes. Such immune escape mutations play an important role in the within-host dynamics of chronic pathogens (e.g. HIV) and are also observed during acute IAV infection1618212426We combine 295 representative human IAVs and the compendium of CTL epitopes into an antigenic map that tracks the long-term evolution of CTL epitopes in IAV across the H1N1, H2N2 and H3N2 subtypes . Each vi2 = 0.93, 4As a measure of immune similarity we use the Jaccard index, defined as the number of epitopes shared by a pair of viruses divided by their number of unique epitopes (Methods). This measure is attractive biologically as it is based on overlaps of epitopes between viruses, and counts any mutation in an epitope as a CTL escape. Multidimensional scaling (MDS) based on Jaccard distances yields a map in which the distance between any pair of viruses represents the expected number of different epitopes . The mapIn the CTL antigenic map, a time directional evolutionary path runs from the early A/1932 (H1N1) to the recent A/2015 (H3N2), with the H2N2 subtype located between the H1N1 and H3N2 subtypes . The higThe early H3N2 viruses (1968–1970) are remarkably close to the previously circulating H2N2 viruses , and find that the total number of epitopes per virus decreases over time . In H3N2The decrease in the number of CTL epitopes could possibly be due to an underrepresentation of recently emerged epitopes which may be less likely to be identified than CTL epitopes in old viruses. However, the number of non-immunogenic peptides is constant over time , suggestIn addition, we obtain an independent test by computationally predicting potential CTL epitopes. These predictions are free from any observational bias that may be present in the set of empirical epitopes. In the analysis we use prediction tools based on HLA-peptide binding affinitiesThe loss of CTL epitopes is the long-term net result of a continuous and rapid turnover of epitopes . In the By combining CTL epitope data with IAV sequence data, we provide evidence that IAV evolves to escape preexisting cellular immunity in the population. Namely, mutations accumulate more rapidly in epitopes than in non-immunogenic peptides, and the total number of epitopes decreases over time .Mutations in epitope sites can result in two different types of escape. First, T-cell receptor (TCR) escapes prevent memory T cells to recognise the mutated epitope. In this case the virus circumvents preexisting memory responses against the epitope in the population, but can trigger the expansion of other immune responses upon infection. The second type are escapes that prevent loading of the epitope. This happens when the mutation either prevents HLA binding or the processing of the epitope. In this case the host cannot elicit any T-cell response against the epitope. Combinations of these escapes are also possible when the mutation lowers the TCR as well as the HLA binding affinity.In our analysis we treat both escapes equally, since the exact impact of the mutations is unknown. This might be an oversimplification, because some of the mutations may hardly affect the binding with either TCR or HLA. However, experiments have shown that CTL escape mutations usually affect the immune response161718et al.The adaptation to preexisting CTL immunity that we observe is in agreement with a recent study showing positive selection at CTL epitope sites in NP by a comparison of evolutionary rates in swine and human IAVsAt this stage the impact of the lower number of CTL epitopes in IAV is unknown, as there are no studies done showing changes in the virulence of influenza. Correlating incidence data with epitope escapes is complex, since other factors, like vaccination and the rapid antigenic drift due to neutralising antibodies1112We speculate that the decrease in the number of CTL epitopes has been ongoing since the global selective sweep of the internal proteins of IAV in the late 1800sEscaping humoral immunity releases IAV from antibody-mediated selection pressures generated by viruses circulating in the recent past4www.gisaid.org; July 2015)We collected human IAV sequences  from the GISAID EpiFlu database from the period 1932–2015 We downloaded the epitope data from IEDB by using the filters ‘human’ as host organism and ‘Influenza A virus’ as source organism and selecting ‘Linear epitopes’, ‘MHC Class I’ and ‘T Cell Assays’ .We concatenated the protein sequences for each virus and perform a global alignment using the Clustal Omega packageet al.N viruses as elements of a low dimensional Euclidean space  increases  to be alike for HLA alleles with similar binding motifs, we used a statistical model that corrects for these dependencies when determining the significance of the mean decrease per HLA allele. We assume that ∑ is the covariance matrix describing the above mentioned dependencies. We calculate ∑ using the similarities between the binding motifs as follows: a HLA allele i can be represented as a binary string bi indexed by all 9-mers p so that p is predicted to bind i, and 0 otherwise. We then choose s > 0, and obtain maximum-likelihood estimates for the mean decrease μ and scaling parameter s. This model is selected in favour of a model that assumes independence of the HLA alleles . The maximum likelihood estimates of the mean decrease and corresponding 95% confidence intervals are given in Since we expected that the change in the number of binders .


SAHARA-J: Journal of Social Aspects of HIV/AIDS exceptionally well and ensured its swift transition to Scholar One. He did so with great enthusiasm and passion right up to him being diagnosed with a debilitating illness that led to his untimely passing. Dimitri diligently set up and refined the internal systems, structures, processes and marketing tools for the journal’s effective and efficient management and was instrumental in acquiring higher impact factor for the journal. Dimitri’s death is a great loss, not only for SAHARA J but also on a personal level as he had become an all-time friend, my confidant and soul brother.Dimitri managed