To investigate the effect of air-drying pressure during ceramic primer coating on zirconia/resin bonding and the surface characteristics of the primed zirconia.a) of primed zirconia were evaluated using spectroscopic ellipsometry (n = 6), optical profilometry and environmental scanning electron microscopy (ESEM) (n = 6), respectively.Two ceramic primers  were applied on the surface of air-abraded zirconia  and dried at 4 different air pressures (0.1–0.4 MPa). The primed zirconia ceramic specimens were bonded with a resin-based luting agent . Micro-shear bond strengths of the bonded specimens were tested after 3 days of water storage or 5,000× thermocycling (n = 12). Failure modes of the fractured specimens were examined with scanning electron miscopy. The effects of air pressure on the thickness of the primer layers and the surface roughness . Compared to vigorous drying conditions, Z-Prime Plus air-dried at 0.2 MPa exhibited significantly higher µSBS (p<0.05). Increasing air-drying pressure reduced the film thickness for both primers. Profilometry measurements and ESEM showed rougher surfaces in the high pressure subgroups of CCP and intermediate pressure subgroup of ZPP.Air-drying pressure influences resin/zirconia bond strength and durability significantly. Higher air-drying pressure (0.3-0.4 MPa) for CCP and intermediate pressure (0.2 MPa) for ZPP are recommended to produce strong, durable bonds between resin cement and zirconia ceramics. Interest for using advanced ceramic materials for dental applications including orthodontic brackets, posts, implant abutments, and restoration frameworks has increased substantially in recent years. Among the different types of ceramic materials, zirconia has attracted the most attention because of its superior mechanical properties and esthetics Due to the lack of amorphous silica in zirconia, traditional bond strength-increasing methods, such as the application of hydrofluoric acid to selectively dissolve the silica phase, and the use of silane coupling agent to create chemical bonding between the silica phase and resin cements, are not suitable for the bonding of zirconia Recently, 10-MDP was introduced into ceramic primers and used together with carboxylic acids, silanes or other adhesive resin monomers to promote chemical bonding to zirconia 2O3 particles  under a pressure of 0.3 MPa  for 15 s with the tip inclined approximately 45° and at a distance of 10 mm from the zirconia surface, and ultrasonically cleaned in 99% ethanol for 10 min Zirconia cylinders  were cut into disk-like specimens (5 mm diameter and 2 mm thick) and embedded in epoxy resin blocks . The surface of the zirconia specimens were polished with silicon carbide papers (from 180-grit to 2000-grit) under water cooling, air-abraded with 110 µm AlOne hundred and ninety-two specimens were randomly divided into two groups according to the primer used: a silane/10-MDP-combined primer  and a primer consisting of 10-MDP and carboxylic acid monomers . Each group was divided into four subgroups according to the air-dried pressures used . One drop of the ceramic primer was applied on the surface of the specimen, left to react for 1 min and air-dried for 10 s with the nozzle swept and inclined approximately 45° and at a distance of 10 mm from the surface. A pressure gauge was connected to the triple syringe to control the pressure of the output oil-free air.2. All specimens were stored in distilled water for 3 days at 37°C. Half of the specimens in each group were used for immediate micro-shear bond strength test and the other half of the specimens were subjected to thermocycling aging treatment before bond testing (n = 12). Thermocycling was performed for 5,000 cycles between 5.0±0.5°C and 55±0.5°C, with 20 s dwell time in each water bath, and 2 s in transfer time To control the bonding area for micro-shear bond test, tygon tubes  with an internal diameter of 0.8 mm and 2 mm in height were placed on the primed zirconia surfaces. The lumens were then carefully filled with a 10-MDP containing resin cement . The resin cement was light-cured for 40 s using a light-curing unit  with an output intensity of 800 mW/cmA universal testing machine  equipped with a customized fixture for stabilizing the specimen and for gripping the resin cement cylinder was used for micro-shear bond strength test . LoadingThe fracture surface of representative specimens was sputter-coated with gold–palladium  and examined using scanning electron microscopy . Failure modes were recorded as: adhesive failure (failure occurring at the zirconia-cement interface) and cohesive failure (failure within cement). Failure areas of each mode were calculated as described previously a<10 nm) and highly reflecting electropolished silicon wafer (10 mm×10 mm), and then air-dried with different pressures  for 10 s. Specimens which were only applied with primer but without air-drying procedures were used as the control.The effect of air-drying pressure on the thickness of the coated primer film was determined using a spectroscopic ellipsometer  equipped with a He-Ne laser source (λ = 632.8 nm) at 70° incidence angle a) of the primer-coated zirconia was examined with an optical profilometer . Briefly, the primer was applied on the air-abraded zirconia, left to react for 1 min and air-dried for 10 s with different pressures . Air-abraded zirconia specimens without primer application and air-drying were used as the control. Three-dimensional images in 3 different regions (350 µm×350 µm) of each zirconia surface were obtained with the optical profilometer and the surface roughness was analysed with the TalyMap Gold software (Taylor Hobson).The effect of air-drying pressure on the average surface roughness  at 10 kV in low vacuum mode (4.6 Torr) to characterize the topographical changes of zirconia surfaces.Data from the µSBS test were analysed with three-way analysis of variance (ANOVA) to examine the effects of primer type, air-drying pressure, thermocycling, and the interaction of these three factors on bond strength. The two-way ANOVA was employed for analysing the data (effects of primer type and air-drying pressure) derived from the primer film thickness measurement and surface roughness measurement. For these analyses, post-hoc pairwise comparisons were performed using the Tukey test. The Pearson correlation test was performed to evaluate the significance of the correlation among the primer film thickness, surface roughness and air-drying pressure. Statistical analyses were performed using the SPSS 13.0 software package . All for analyses, statistical significance was preset at α = 0.05.The results of µSBS tests are shown in After thermocycling, for the CCP group, decrease in µSBS after thermocycling only occurred in the 0.1 MPa and 0.2 MPa subgroups (p<0.05), while for the 0.3 MPa and 0.4 MPa subgroups, there were no significant differences between the µSBS before and after thermocycling (p>0.05). The highest µSBS in the CCP group after thermocycling was achieved in the 0.3 MPa subgroups (32.4 MPa) (p<0.05). For the ZPP group, the µSBS of different air-pressure subgroups were all significantly decreased after thermocycling (p<0.05), with the 0.4 MPa subgroup being the lowest (8.7±3.9 MPa) and the 0.2 MPa subgroup being the highest (21.6±2.7 MPa) (p<0.05).Scanning electron microscopy images of representative failure modes are shown in The results of primer film thickness  revealeda) values of the experimental subgroups and sandblasted zirconia without primer application (NP) are shown in The results of ESEM observation  of the sThe raw data of micro-shear bond strength, primer film thickness and surface roughness are shown in in vitro study evaluated the effect of air-drying pressures during primer coating on the resin-zirconia bond strength and the surface characteristics of the primed zirconia surfaces. It was found that higher air-drying pressures during primer coating resulted in thinner primer layers, rougher surfaces of the primed zirconia, higher bond strength and better durability of the bond between resin cement and primed zirconia. Thus, the null hypothesis that air-drying pressure has no effect on the bond strength of the zirconia/resin bonding and the surface characteristics of the primed zirconia has to be rejected.The present 110 µm Alumina powder sandblasting was performed to standardize the zirconia surface in the present study. Although the negative effect of the microcracks on the zirconia surface caused by this surface pretreatment, sandblasting is believed beneficial to zirconia bonding by increasing the surface roughness, bonding area and remove any contaminants from the ceramic surface Z-Prime Plus is a proprietary formula of both nonvolatile hydrophilic  and hydrophobic (Bis-GMA) resin monomers dissolved in ethanol and water. Carboxylic monomer is another acid adhesive resin monomer employed in ZPP to assist 10-MDP in chemically interacting with zirconia After thermocycling, a significant reduction in bond strength and predominant adhesive failure were found in all subgroups of ZPP. Hydroxyethyl methacrylate, the co-solvent present in ZPP, is included in the ceramic primer for minimizing phase separation and increasing the miscibility of hydrophobic and hydrophilic resin components It must be noted that only one aging condition (thermocycling) was performed to evaluate the durability, stability, and hydrolytic degradation of the resin-ceramic bond. This may be considered one of the limitations of the current study as long-term water storage may significantly affect the bonding durability Within the limitations of the present study, it may be concluded that application of a relative high air-drying pressure during ceramic priming is necessary to achieve strong and long-term bonding between resin cement and zirconia. There exists an optimal air-drying pressure for each ceramic primer for forming strong durable bonds between resin cement and zirconia ceramics.Figure S1a) Prior to micro-shear bond test, the tygon tubes around the resin cement cylinders were removed, by gently cutting the tubes into two hemi-cylinders using a feather blade. (b) Specimens were clamped with the custom fixture and tested in a universal testing machine . A thin wire (diameter 0.2 mm) was looped around the resin cement cylinder, making contact through half of its circumference and was gently held flush against the resin/zirconia interface. A shear force was applied to each specimen at a cross-head speed of 0.5 mm/min until failure occurred. The resin-zirconia interface, the wire loop and the center of the load cell were aligned as straight as possible to ensure the desired orientation of the applied shear test force.Schematic diagram of micro-shear test. ((TIF)Click here for additional data file.Table S1List of materials used in the present study.(DOC)Click here for additional data file.Table S2Subgroups and primer-coating protocols used in the present study.(DOC)Click here for additional data file.Data S1The raw data of micro-shear bond strength, primer film thickness and surface roughness in this study.(XLS)Click here for additional data file.


International Journal of Clinical and Experimental Pathology [The editors are retracting this article  as it haathology  and it i


To evaluate the in vivo corneal changes using in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) in patients with Fuchs’ dystrophy who underwent Descemet stripping automated endothelial keratoplasty (DSAEK) and the relationship between these changes and the postoperative visual recovery up to 1-year follow-up.Before DSAEK and 1 day, 3, 6 and 12 months after surgery 31 patients (39 pseudophakic eyes) underwent a complete ophthalmological evaluation including best corrected visual acuity (BCVA), IVCM  and AS-OCT (graft thickness).P = 0.002), interface haze , postoperative subepithelial haze  were significant.Graft thickness measurements by AS-OCT were strongly correlated to those obtained using IVCM at every follow-up stage . No correlation between BCVA and graft thickness measured by AS-OCT at any follow-up stage was found, while at 3 and 6 postoperative months the correlations between BCVA and preoperative subepithelial haze (r = 0.61, P < 0.001 and r = 0.46, The study confirmed corneal subepithelial haze and interface haze as important factors limiting visual acuity after DSAEK, while graft thickness was not related to BCVA. Notwithstanding the growing interest on Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK) is still one of the treatment of choice for Fuchs’ corneal endothelial dystrophy. This surgical technique allows the selective replacement of the posterior dysfunctional part of the cornea, including endothelium, Descemet membrane and a variable small amount of posterior stroma , 2.This technique has shown several advantages over penetrating keratoplasty (PK): it has been reported to cause lower astigmatism, lower suture-related complications than PK –5, fewerAmong the most used devices to evaluate these parameters are anterior segment Optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM).AS-OCT is a diagnostic method widely used in ophthalmology and a non-invasive useful device in DSAEK follow-up. It allows to evaluate graft adhesion in the immediate postoperative period and to measure graft and corneal thickness , 26.IVCM is a non-invasive diagnostic test that allows to acquire images of all the corneal layers  and of their cellular components  . It is tThe purpose of our study was to evaluate the in vivo corneal changes using white-light IVCM and time domain AS-OCT in patients with Fuchs’ endothelial dystrophy who underwent DSAEK and the relationship between these changes and the postoperative visual recovery up to 1 year follow-up.This prospective cohort study involved 39 pseudophakic eyes of 31 patients who underwent DSAEK surgery due to Fuchs’ corneal endothelial dystrophy at the Eye clinic, Careggi University Hospital of Florence, Italy, between March 2011 and September 2012. The study followed the tenets of the Declaration of Helsinki and was approved by the local ethic committee . All patients signed a surgical informed consent form before DSAEK and an informed consent for the study.Exclusion criteria for this study were concurrent eye pathology as glaucoma, macular/retinal diseases significantly affecting visual acuity, amblyopia, optic neuritis, uveitis, scleritis, ocular infection, pre-existing severe corneal scarring.At the preoperative visit all patients underwent a complete ophthalmological evaluation including best corrected visual acuity , slit lamp biomicroscopy, intraocular pressure measurement, fundus ophthalmoscopy, white light IVCM  and time domain AS-OCT .IVCM was performed with a 40 X magnification and the z-ring adapter . Lamp brBefore the exam, a drop of topical anesthetic (Benoxinate) was instilled. The patient was then asked to steadily fixate a target and IVCM was performed on the central cornea. The exam lasted approximately 3 min. At the end of the examination, an antibiotic eye drop (gentamicin 0.3 %) was administered.The preoperative subepithelial haze was measured as the mean between the peak value of LRU (light reflectance units) in the subepithelial area and the values at 25 microns in the endothelial direction and 25 microns in the epithelial direction. Since at each examination Confoscan 4 performed three different scans of the cornea, three mean values, one for each scan, were obtained and averaged.Two trained investigators performed the examination and one masked investigator selected and analyzed IVCM and AS-OCT scans.All patients underwent DSAEK surgery alone.All procedures were performed under monitored anesthesia with peribulbar block.The posterior lamellar grafts were supplied from the Cornea Bank of Lucca , after having been cut by a microkeratome with a a 350-micron head .2. Graft thickness provided by the Bank was recorded.They were trephinated by the surgeon with a Hessburg-Barron donor corneal punch  to a diameter of 8.25–8.75 mm. All grafts had an endothelial cell count of at least 2500 cells/mmThe anterior chamber of the eye was then entered through a 4 mm clear corneal incision, and in order to prevent the anterior chamber collapse a maintainer was used. Descemet membrane was stripped from the central 8-8.5 mm diameter. The rolled endothelial graft was inserted using a Busin glide  and a small air bubble that was injected to lift the graft. After centering the graft, the anterior chamber was completely filled with an air bubble that after 10 min was reduced to about the 80 % of the size of the endothelial graft.All surgical procedures were performed by the same skilled surgeon, RM.Patients were evaluated 1 day, 1 week, 1 month, 3, 6 and 12 months after surgery. Whereas each visit consisted of complete ophthalmic examinations, including BCVA and slit-lamp examination, at 3, 6 and 12 month visits AS-OCT (graft thickness measurement) and IVCM  were also performed.Graft thickness was measured by IVCM by assessing the distance from the endothelium to the change of reflectance that suggests the beginning of donor-recipient interface, then calculating the mean between the values obtained in each of the three scans performed by IVCM at each examination. The donor-recipient interface was identified as the area where a change in cell morphology and/or extracellular matrix was detected.The donor-recipient interface haze, the characteristic gain in reflectance that may be observed at the border between the donor graft and the recipient cornea, was also evaluated by IVCM. It was measured as the mean between the peak value of LRU at the interface and the values at 25 microns in the endothelial direction and 25 microns in the epithelial direction; then we averaged the three mean values obtained, one for each scan.Postoperative subepithelial haze was measured as already described in the preoperative evaluation section.Graft thickness was measured by AS-OCT on a horizontal cross sectional image obtained at the anterior corneal vertex, using the software-imbedded flap-tool .Linear mixed models were used to compare the change of the covariates of interest  at various follow-up times, accounting for correlated data using time as a random slope at the subject level. In order to simultaneously assess the correlation between covariates at different follow-up times, while accounting for individual correlation, structural equation modeling (SEM) of standardized variables was performed. Intraclass correlation coefficient (ICC) was used to compare graft thickness measured by means of AS-OCT and IVCM.All analyses were carried out using Stata software .Results were expressed as mean and standard deviation (SD). A value of P < 0.05 was considered statistically significant.The mean age of the patients was 73 ± 9.3 years (55 to 81 years).BCVA gradually improved during the follow-up Fig. : the meaMean graft thickness was 132.3 μ (SD = 32.7 μ) at baseline, as measured by the Eye Bank using Visante AS-OCT.P = 0.022 at 3 months, P < 0.001 at 6 and 12 months) was observed. In comparison with the 3-month value, graft thickness reduction was not significant at 6 months (P = 0.069), while it was significant at 1 year (P < 0.001).During follow-up Fig. , a statiP = 0.026 and P = 0.003, respectively).Graft thickness measured by IVCM decreased significantly at 6 months and 1 year . IVCM yielded slightly but significantly thicker measures compared to AS-OCT at 3 months , 6 months  and 12 months .In Fig. Preoperative mean subepithelial haze was 133.0 LRU (SD = 33.3 LRU).P = 0.006 at 6 months, P = 0.003 at 1 year) were found, as well as a significant postoperative subepithelial haze reduction   was observed.Even though graft thickness measured by AS-OCT and BCVA at any follow-up stage were not significantly correlated , a modest correlation between the reduction of graft thickness and the improvement of BCVA between month 6 and month 12 , while it was no more significant at month 12   Fig. .Fig. 6ReP = 0.003 at 6 months), whereas there was no correlation at 1 year   Fig. .P = 0.004 at 3 months; r = 0.39, P = 0.001 at 6 months)  Fig. , while aP = 0.008) was also observed.A correlation between the decrease of subepithelial haze and the improvement of BCVA between 6 months and 3 months  and between 12 and 6 months  and at 6–to–12 months (P = 0.001). Interface haze reduction positively affected BCVA at 6-to-12 months (P = 0.013) only.Finally, we checked whether the interval change in BCVA at 3-6 months and 6–12 months was simultaneously related to that of graft thickness and subepithelial and interface haze. This confirmed that an improvement of BCVA was not associated with graft thickness change, whereas a significant association was found with a reduction of subepithelial haze both at 3–to–6 , that can be mainly located in the subepithelial region and in the graft-host stromal interface , 30, 36.The subepithelial haze is a common finding to several corneal abnormalities, such as Fuchs’ endothelial dystrophy or other chronic endothelial dysfunction, and it has been related to tissue changes such as fibrosis caused by chronic edema , 36; togIn our study we found a correlation between preoperative subepithelial haze and BCVA at 3 and 6 month follow-up, and between postoperative subepithelial haze and BCVA at the same visits. We found also a correlation between the change of postoperative subepithelial haze and that of BCVA between 6 months and 3 months and between 12 and 6 months, suggesting that it can be an important factor limiting DSAEK visual outcome.Since the preoperative subepithelial haze can affect postoperative visual outcome , and a correlation between the amount of the subepithelial haze with the duration and the severity of corneal edema in the host cornea before surgery and between patients’ age and visual outcome has been found , 36, we Also donor-recipient interface haze has been assumed to affect visual outcome after endothelial keratoplasty , 37, 38;Several instruments has been recently used to measure corneal haze or backscatter, such as Scheimpflug Camera , 37 and Our study confirmed the subepithelial haze and the interface haze as important factors limiting visual acuity after DSAEK, while central graft thickness was not related to BCVA. No correlation between these parameters was found at 1 postoperative year, maybe due to the reduced range of visual acuity reached after the gradual improvement observed during the follow-up and to the limited number of patients.Limitations of our study are the lack of the aberrometric evaluation of postoperative quality of vision and the short follow-up.Further larger studies are necessary to investigate the role of corneal haze and other parameters in affecting not only visual acuity but also visual quality after DSAEK, and to assess their impact in patients’ quality of life after DSAEK.


Philosophical Transactions of the Royal Society B has been commissioned to mark the Royal Society's celebration of the 350th anniversary of the publication of the first issue of Philosophical Transactions, the world's oldest scientific journal. The issue is designed both to look back at some major, historical, scientific landmarks in the biological sciences published in the journal, and to consider their ramifications for modern understanding and research. A corresponding special issue of Philosophical Transactions A, covering the physical, mathematical and engineering sciences, has also been produced [This special issue of produced .Philosophical Transactions was published under the visionary editorship of Henry Oldenburg, a theologian and polymath from the German Hanseatic town of Bremen, who was also the first Secretary of the Society. The information presented in the first volume [1Some 2 years after its formation, ‘The Royal Society of London for Improving Natural Knowledge’ was granted an addition to its charter by King Charles II, allowing it to publish. On 6 March 1665, the first issue of Philosophical Transactions from that year was destroyed, although thankfully copies still survived outside London. Samuel Pepys, diarist and later President of the Royal Society, rushed to save his own papers from the fire, for there were often no second copies of the notes and correspondence that had acted as a record and established priority on ideas and observations in the days before scientific publishing. The journal eventually became an important source of revenue for the Society, although its finances have at many times since been precarious, and the editorship in those hardship times required an unusual level of devotion to the cause. Appropriate acknowledgement of scientific precedence was also a requirement for publication, and Oldenberg instituted the practice of sending submitted manuscripts to other experts for commentary and feedback to authors, helping to establish today's practice of peer review.The journal has changed considerably in its 350 years, although important features of modern scientific publishing were present from the beginning. At the outset, the journal focused on the latest scientific discoveries and development, and often reported on current, rather than on finished, research. Accurate recording of empirical observations and experimental measurements was paramount, and regarded as the route to understanding the true nature of things. The importance of the archival function of scientific journals became painfully apparent with the Great Fire of London in 1666, when the prospect of all knowledge being lost must have seemed all too real. Indeed, all the remaining stock of Philosophical Transactions, then still officially an independent publication, were subject to biting satires from writers such as Jonathan Swift. The journal was brought under direct Royal Society control in 1752, and renamed as the Philosophical Transactions of the Royal Society in 1786. Further reform followed in the nineteenth century, when Charles Babbage wrote an open letter, denouncing fellows who used the Royal Society as a social club, and calling for a new category of fellow: working scientists who published their work in Philosophical Transactions. By the late 1830s, peer review was tightened, usually involving two or more referees, who could include the Editor, a position then still held by the Secretary of the Society.The Royal Society itself underwent something of a dip in the first half of the eighteenth century, when both it and Philosophical Transactions A, covering the physical sciences and Philosophical Transactions B, covering the biological sciences. In the late twentieth century, much of the administrative and marketing work for the journals was taken on by in-house publishing editors, with a fellow apiece at the helms of Philosophical Transactions A and B, supported by large, international and diverse editorial boards of fellows and other scientific experts. The modern Philosophical Transactions B also provides a uniquely strong context for the papers that it publishes, by grouping them into themed volumes, on topics of current scientific opportunity and rapid progress and of policy importance, sometimes based on the talks given at Royal Society discussion meetings.By 1887, the breadth and volume of science had grown so much that the journal split into two—Philosophical Transactions in the years since 1665 (physical sciences papers are covered in the corresponding issue of Philosophical Transactions A [Each commentary in this issue considers a key scientific discovery in biological sciences that was published in Selecting the papers to include in the volume was not an easy task, because we were confronted with a plethora of strong contenders. We wanted to ensure a reasonable historical spread, and we strove to balance different research areas, which did result in the exclusion of some classic publications in well-represented areas. There is also a woeful lack of publications by female scientists, mainly a sign of the times.Philosophical Transactions B journeys through these latest developments, both we who have the honour to edit the journal, and the powerful teams of scientists and publishers with whom we work, will strive to ensure that the future of the journal is even more remarkable and successful than its past.The landscape of scientific publishing has changed rapidly in recent years and continues to do so. As


The outcome of functional Magnetic Resonance Imaging (fMRI), Magneto-encephalography (MEG) and particularly, non-invasive mapping methods such a Transcranial Magnetic Stimulation (TMS) are described and the variability of FEF localization across individuals and mapping techniques are discussed. In the second part of this review, we will address the role of the FEF. We explore its involvement both in the physiology of fixation, saccade, pursuit, and vergence movements and in associated cognitive processes such as attentional orienting, visual awareness and perceptual modulation. Finally in the third part, we review recent evidence suggesting the high level of malleability and plasticity of these regions and associated networks to non-invasive stimulation. The exploratory, diagnostic, and therapeutic interest of such interventions for the modulation and improvement of perception in 3D space are discussed.The planning, control and execution of eye movements in 3D space relies on a distributed system of cortical and subcortical brain regions. Within this network, the Eye Fields have been described in animals as cortical regions in which electrical stimulation is able to trigger eye movements and influence their latency or accuracy. This review focuses on the Frontal Eye Field (FEF) a “hub” region located in Humans in the vicinity of the pre-central sulcus and the dorsal-most portion of the superior frontal sulcus. The straightforward localization of the FEF through electrical stimulation in animals is difficult to translate to the healthy human brain, particularly with non-invasive neuroimaging techniques. Hence, in the  The frontal eye field (FEF) is an area of the frontal cortex in animals over which electrical stimulation is able to trigger eye movements. Electrophysiological studies in the monkey defined the FEF as an area containing visual, motor, and visuo-motor cells  will modulate the involvement of the FEF. Indeed, different cortical oculomotor areas are differentially recruited according to the category of eye movements  and how its activity can be modulated for clinical purposes (part III), we will describe the efforts made to localize this area in both non-human and human primates (part I). As expected from an area contributing to numerous functions, the exact localization will strongly depend on the methods and specific paradigms used to assess it.The primate FEF is defined physiologically as the portion of the dorsolateral prefrontal cortex from which low-intensity intracortical stimulation is able to elicit rapid eye movements. Using this invasive approach, the monkey FEF has been located by some studies in the frontal lobe along the anterior border of the arcuate fissure, which would correspond to Brodmann's area 8, or overlapping with both areas 8 and 6  , positron emission tomography (PET), magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS). A summary of the localizations reported in these studies can be found in Table In the superior frontal convolution, in advance of the centre for certain forward movements of the arm, as well as in the corresponding part of the middle frontal convolution, are areas, stimulation of which causes lateral (crossed) movements of the head and eyes and dilatation of the pupils.”  than the human FEF, localized mainly thanks to neuroimaging studies (Brodmann's area 6). A suggestion to reconcile such discrepancies between monkey and human reports is that the more posterior FEF location in humans has been erroneously attributed to Brodmann's area 6. Following that line, a study focused on the delimitation of cytoarchitectonics areas in post-mortem human brains containing the superior element of the pre-central sulcus and the caudal end of the superior frontal sulcus . Do monkey fMRI recordings also reveal similar activations than the ones shown in humans with this same mapping technique? Koyama et al.  conducteFinally, the use of a third methodology can shed a new light on the interpretation of results arising from monkeys' microstimulation and humans' fMRI studies. Taking advantage of the exquisite temporal resolution of MEG and the possibility of localizing source signals with a reasonable spatial resolution Ioannides et al. , 2005 suonline) or lasting  facilitatory or disruptive impact on neurophysiological activity and consequently on the performance driven by the targeted cortical region and its associated network of areas , i.e., the intensity at which they induce overt evoked hand muscle activations in half of the trials when stimulating the primary motor cortex. Like in microstimulation studies, the choice of intensity is somehow arbitrary. Indeed, it is likely that simulating at 100 or 120% of RMT will lead to different results. More importantly, stimulating at an intensity based on the RMT does not warrant consistent results across participants as it is known that, except under certain circumstances  and successfully reported significant effects on quantitative measures of eye movements , the gold standard would be to use a similar mapping methodology to identify the exact location of this region prior to its manipulation. Based on this notion, for instance, Olk et al.  took theIn conclusion, potential conflicting results across studies concerning the function of the FEF might be related, among other factors, to variability in the way it is localized. This observation has to be kept in mind when interpreting the results that will be presented in the following part.This section will review the role of the FEF in eye movements and in visuo-spatial attention, visual awareness, and perceptual modulation.In humans, knowledge on the role of FEF in several types of eye movements  effects on reaction times and eye movement latencies. Thus, shorter latencies could be related to crossmodal facilitation, whereas longer latencies could result from the participants waiting for TMS discharge as for a “go” signal. Thus, it is important to ensure that the effects on latencies are either stronger or in the reverse direction than the effects obtained in a control condition, such as sham stimulation or the active stimulation of a control brain area unrelated to saccadic control or execution. Using such cautionary measures, TMS over FEF has been shown to modulate the latency of different types of saccades.TMS studies exploring the role of FEF in eye movements are reported in Table In conclusion, non-invasive neurostimulation studies employing TMS largely confirmed, in healthy humans and with higher spatial and temporal resolution, the insights drawn from patient studies. The unquestioned role of the FEF in the triggering of voluntary eye movements as well as the still controversial role of this region in reflexive movement inhibition and initiation is reminiscent of the blurred frontiers between reflexive and voluntary movements and of the importance of entire oculomotor networks for the control of eye movements, in which the relative contribution of each node is modulated by the cognitive context. The rest of this Section on the Role of FEF will explore how the FEF is involved in a very diverse set of higher cognitive functions  ipsilateral to the saccade's direction increased general performance, non-invasive stimulation over the FEF contralateral to the saccade's direction specifically decreased or enhanced discrimination on the target location depending on the exact stimulation parameters  or, on the contrary in switch detection has also been addressed in TMS approaches. Indeed, fMRI experiments reported a suppression of BOLD response in fronto-parietal networks, including the FEF, during simultaneous color and location repetition . The cognitive context modulates the role of the FEF in eye movements but direct report of conscious perception, for instance, is not performed in eye movements studies. Conversely, studies on cognition rarely explore eye movements . In future studies, exploration of microsaccades and other fixation eye movements  has proven particularly promising. Indeed, both techniques have demonstrated efficacy in modulating transiently brain regional excitability (Nitsche et al., However, the ability of FEF-TMS to increase visual perception and awareness, at least in healthy subjects on a trial-by-trial basis (Grosbras and Paus, The existence of fronto-parietal synchronization at specific frequencies associated with attentional processes (Buschman and Miller, Another topic of interest for the treatment of visual awareness disorders would consist in further exploring the link between eye movements and conscious perception. Indeed, eye movements training can be natural way to activate the FEF and other areas of attentional networks. The resulting plasticity might in turn improve visual awareness. Vergence is particularly fragile and subject to aging, fatigue and neurological insults (Scheiman et al., The link between exploratory movements performed in 3D space and the gathering of visuo-spatial information goes beyond a simple sharing of brain resources. Indeed, efferent copies of vergence movements, proprioception on convergence state (Priot et al., Besides the deficit of awareness in contralesional space, neglect patients seem to also suffer from problems that are specific to the depth at which tasks are performed: neglect symptoms might be sometimes more severe in the near space or in the far space (see Aimola et al., In this review, we focused on the role and localization of the human FEF, a cortical area which is part of highly distributed saccadic and visuo-spatial networks with important bearing on the control of eye movements in 3D space and contributing importantly to several aspects of attentional and visual cognition. A particular emphasis was placed on TMS studies, which have allowed a successful causal exploration of the contributions of this frontal region. We provided evidence that the results of such studies with regards to their ability to map FEF cortical location are not necessarily similar to those of other mapping techniques employed in neuroscience, such as lesion studies, microstimulation, intracranial recordings, PET, fMRI, and EEG/MEG in both humans and non-human primates. Similarities and discrepancies across the results provided by different techniques, the use of different paradigms and/or experimental models were presented and discussed. Finally, we speculated on the posibility to manipulate FEF activity with non-invasive neurostimulation and oculomotor training in order to improve visuo-spatial awareness in 3D space in healthy population and to promote functional recovery in stroke patients.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In recent years there has been an improvement of zirconia ceramic materials to replace posterior missing teeth. To date little in vitro studies has been carried out on the fracture resistance of zirconia veneered posterior fixed dental prostheses. This study investigated the fracture resistance and the failure mode of 3-unit zirconia-based posterior fixed dental prostheses fabricated with two CAD/CAM systems. Twenty posterior fixed dental prostheses were studied. Samples were randomly divided into two groups (n=10 each) according to the zirconia ceramic analyzed: Lava and Procera. Specimens were loaded until fracture under static load. Data were analyzed using Wilcoxon´s rank sum test and Wilcoxon´s signed-rank test (P<0.05). Partial fracture of the veneering porcelain occurred in 100% of the samples. Within each group, significant differences were shown between the veneering and the framework fracture resistance (P=0.002). The failure occurred in the connector cervical area in 80% of the cases.  All fracture load values of the zirconia frameworks could be considered clinically acceptable. The connector area is the weak point of the restorations. Key words:Fixed dental prostheses, zirconium-dioxide, zirconia, fracture resistance, failure mode. The porcelain fused to metal represents the gold standard technique for posterior fixed dental prostheses (FDPs). However, with the increasing demand in esthetic restorations, and the introduction of computer-aided design/computer-aided manufacturing (CAD-CAM) technology in dentistry, in the last years the use of ceramic restorations has been increased . TherefoAlthough the good mechanical properties of zirconia allow the construction of posterior FDPs, the core-veneer interface is one of the weakest aspect of these restorations ,5 so thaThe aim of the present study was to compare the fracture resistance (FR) of two zirconia CAD/CAM systems with their corresponding porcelains and the failure mode of 3-unit zirconia posterior fixed dental prostheses (FDPs) with an intermediate pontic. The null hypothesis was, that no differences would be found in the fracture resistance and the failure mode between the zirconia systems.Twenty standardized specimens with 2 abutments and screwed onto a platform  were prepared from stainless steel to receive posterior 3-unit FDPs with an intermediate pontic (spanning the first premolar to the first molar). The abutments were prepared with 5 mm in height, a 1 mm wide chamfer, and a 6 degrees angle of convergence of the axial walls. The specimens were used as working dies and randomly divided in 2 groups (n=10 each). Two zirconia materials and two veneering porcelain were used: Group 1 (L) Lava All-ceramic System and Lava Ceram (respectively)  and Group 2 (P): Nobel Procera Zirconia and NobelRondo (respectively) . The size of the connector area was 3 mm x 3 mm and the frameworks thickness was 0.5 mm, with a space of 50 µm for the cement agent. The digitization of the specimens was performed using an optical scanner in the L group  and a mechanical scanner in the P group .Samples fabricated with each zirconia system were luted onto the master dies at room temperature with glass ionomer cement . The cement was placed on the axial surfaces of the abutments and a standardized load of 10 N was applied for 10 minutes with a dynamometric key  to ensure the correct distribution of the cement and to seat the FDPs properly. The cemented FDPs were stored in water for 1 week at 37 °C.All FDPs were subjected, according to the ISO 6872:2008, with a three-point bending test until fracture using a universal testing machine  at a crosshead speed of 0.5 mm/min. Axial compressive loads were applied at the central fossa of the FDPs´ pontic. Data of the veneering ceramic fracture  and total fracture of the FDPs were automatically recorded. The force was measured in Newton (N). After testing the location of the fracture was examined visually and with a stereomicroscope (x15).P < 0.05. All statistical analyses were handle with SAS 9.2 .The Wilcoxon rank sum test and the Wilcoxon signed-rank test were run for FR (N) comparisons. Statistical significance was set at P=0.07). Significant differences in the fracture resistance of the veneering ceramic were recorded between both groups (P=0.0023). The fracture resistance of the veneering ceramic and the total FR were significantly different within each experimental group (P=0.002). The L group showed the highest mean value.Regardless of the zirconia system used, the failure mainly occurred at the cervical area of the connector (80%) Fig. . In bothThe present study analyses the fracture resistance of two zirconia systems and no differences were observed in total fracture, but differences were shown for veneering ceramic between the groups thus the data support the partially acceptance of the null hypothesis.Little in vitro studies have been carried out regarding the strength of frameworks and porcelain veneering on zirconia posterior FDPs. The study results indicate that in all the specimens and in both zirconia systems the veneer porcelain fractures at a lower load than the framework, with significant differences in fracture values between the veneer and the framework. These results are in accordance with previous studies in which failure of the porcelain layer before failure of the framework material was observed ,7-11. ThIn the present study, the Procera group revealed predominantly adhesive failure between the zirconia core and the veneer ceramic in 6 specimens and adhesive failure mode in 4 specimens, but in the Lava group, the failure pattern was predominantly cohesive, in agreement with previous studies in which the most frequent type of fracture occurs within the porcelain veneer rather than at the porcelain-zirconia interface ,11,16-20Different factors may influence and/or cause the fracture of the veneering porcelain as differences in termal expansión coefficients between core and ceramic, flexural strength of the veneering ceramic, firing shrinkage of ceramic, porcelain thickness, surface treatament of the framework, flaws on veneering and pour wetting by veneering on core ,9,12,15.Despite the many disadvantages of in vitro studies, it is important to evaluate isolated mechanical properties under standardized conditions . In thisThe most common fracture pattern of tested zirconia-based FDPs was at the loading point and through one or both connectors, being the iniciation of fracture in the gingival embrasure ,22,25-27Further laboratory and clinical studies are needed to evaluate the veneering porcelain on the fracture process of zirconia FDPs.Within the limitations of this in vitro study, it can be concluded that the fracture resistance of the veneering ceramic of zirconia structures depends on the zirconia system used. The Lava system exhibited the greatest resistance of the veneering ceramic. However, the zirconia system had no effect on the ultimate resistance of zirconia frameworks. All tested groups demonstrated clinically acceptable fracture load values.


Acinetobacter species are assuming an increasingly important role in modern medicine, with their persistent presence in health-care settings and antibiotic resistance. However, clinical reports addressing this issue in patients with peritoneal dialysis (PD) peritonitis are rare.Acinetobacter that occurred between 1985 and 2012 at a single centre were retrospectively reviewed. Clinical features, microbiological data, and outcomes were analysed, with stratifications based upon temporal periods (before and after 2000).All PD peritonitis episodes caused by Acinetobacter species were responsible for 26 PD peritonitis episodes  in 25 patients. A. baumannii was the most common pathogen (54%), followed by A. iwoffii (35%), with the former being predominant after 2000. Significantly more episodes resulted from breaks in exchange sterility after 2000, while those from exit site infections decreased (P = 0.01). The interval between the last and current peritonitis episodes lengthened significantly after 2000 . All the isolates were susceptible to cefepime, fluoroquinolone, and aminoglycosides, with a low ceftazidime resistance rate (16%). Nearly half of the patients (46%) required hospitalisation for their Acinetobacter PD-associated peritonitis, and 27% required an antibiotic switch. The overall outcome was fair, with no mortality and a 12% technique failure rate, without obvious interval differences.Acinetobacter PD-associated peritonitis in our cohort suggested an important evolutional trend. Appropriate measures, including technique re-education and sterility maintenance, should be taken to decrease the Acinetobacter peritonitis incidence in PD patients.The temporal change in the microbiology and origin of  The utilisation of peritoneal dialysis (PD) in end-stage renal disease (ESRD) has been long purported for its economical advantage and similar effects on patient outcomes compared with haemodialysis (HD) Serratia, Providencia, indole-positive Proteus/Acinetobacter/Morganella, Citrobacter, Enterobacter, or Hafnia) denotes a spectrum of organisms with an intrinsic tendency for antibiotic resistance Pseudomonas GNB PD-associated peritonitis, and Acinetobacter species are responsible for <20% of these cases Acinetobacter PD-associated peritonitis might have poorer prognoses compared with the other Enterobacteriaceae members, owing to their high antibiotic resistance rates. However, past reports suggested just the opposite, with technique failure rates of 9% Acinetobacter peritonitis might occur with an immunocompromised status Acinetobacter PD peritonitis are unknown. Utilising a longitudinal PD registry of more than 2 decades in a single centre, we conducted the present study to explore the transition of these parameters over different time periods.Among GNB peritonitis, the acronym SPICE (The ethics committee of the NTUH approved the current study (No. 201212165RINC). The local institutional review board did not mandate patient consent, as no interventions were performed and patient privacy was not breached. The local institutional review board waived the need for written informed consent from the participants.Acinetobacter species PD peritonitis between 1985 and 2012 were selected. Peritonitis was diagnosed according to the presence of symptomatology and cloudy effluent, with a white blood cell count >100/µL and neutrophil percentage >50% In 1985, the National Taiwan University Hospital (NTUH) PD program was established All enrolees’ demographic profiles, including age, sex, and comorbidities , were reviewed Acinetobacter, we documented the PD vintage and modality  and the initial symptoms. Laboratory data during the peritonitis episodes were obtained. Pathogen species and the corresponding antibiogram were identified. The presumptive origins of each peritonitis episode were divided into a break in sterility during the exchange procedure, gastrointestinal (GI) microflora transmural migration, exit site infection/tunnel infection, or undetermined, according to past reports For each peritonitis episode caused by The outcome measures in the present study consisted of primary response, antibiotic switch (secondary response), relapse peritonitis, repeat peritonitis, Tenckhoff catheter removal, and patient death. The primary response was defined as symptomatic improvement of the patient within 3 days of receiving empirical antibiotics, accompanied by effluent leukocyte count <100/µL. The secondary response was defined as a response to the second-line antibiotics when effluent did not turn clear after first-line antibiotic use Acinetobacter species , with an incidence of 1 per 1558 patient-months. One patient developed 2 separate episodes of Acinetobacter peritonitis, and the remaining patients each experienced 1 episode. To delineate the temporal changes of their clinical features, we divided the Acinetobacter peritonitis cohort into 2 phases, those that occurred before 2000 and those that occurred during or after 2000.During the study period, 369 of 1278 chronic PD patients developed 744 episodes of PD-related peritonitis over 40,499 patient-months, with an overall peritonitis incidence of 1 per 54 patient-months . Among the 744 episodes of PD-related peritonitis, 25 patients developed 26 peritonitis episodes from Acinetobacter are listed in Acinetobacter peritonitis were 52 years and 29 months, respectively, without differences between phases. Three-fourths of the patients chose CAPD as their dialysis modality. One-third of Acinetobacter peritonitis patients had DM, but only 12% of patients had HF.The demographic profiles and clinical characteristics of the patients who developed PD-related peritonitis caused by Acinetobacter peritonitis patients included DM (31%) and chronic glomerulonephritis (31%), followed by lupus (4%) and hypertension (4%). No significant difference was found between those that occurred before 2000 and those that occurred after 2000. Only 1 patient had undergone intra-abdominal surgery (cholecystitis with open cholecystectomy) before developing Acinetobacter peritonitis. Another patient received an antibiotic within the month before the current peritonitis episode , and still another lupus patient was receiving prednisolone 10 mg daily.The most common aetiologies of ESRD in the Acinetobacter peritonitis episodes. The current peritonitis episode represented the first peritonitis episode in 62% of the patients, and for those who had already developed peritonitis, there were on average 2 episodes before the Acinetobacter episodes .episodes . No sign latency ; P<0.01.Acinetobacter were abdominal pain (85%), followed by nausea/vomiting (31%), fever (27%), and diarrhoea (15%). All the patients exhibited a turbid dialysate. The mean effluent leukocyte count was 5296/µL , with 95% neutrophils . The initial blood leukocyte levels were 8094/µL , with 82% neutrophils . The most common species from the effluent was Acinetobacter baumannii (54%), followed by A. iwoffii (35%), A. ursingii (4%), and A. junii (4%). A. baumannii was the predominant pathogen after 2000, while A. iwoffii outnumbered the others before 2000 . Coagulase-negative staphylococci and Acremonium species were each responsible for 1 episode of polymicrobial growth. None of the patients had concomitant Acinetobacter bacteremia.The presenting symptoms of PD-related peritonitis caused by Acinetobacter were a break in exchange sterility (19%) and translocation of GI microflora (19%), followed by exit site infection/tunnel infection .The most common identifiable causes of PD-related peritonitis caused by tion 8%; . ApproxiAcinetobacter species are shown in Acinetobacter species were susceptible to aminoglycosides (including gentamicin and amikacin), fluoroquinolones, and a fourth-generation cephalosporin (cefepime) after 1995. Approximately 16% of Acinetobacter species were non-susceptible to ceftazidime, among which three-fourths were resistant. In addition, 8% of isolates showed intermediate resistance to piperacillin, while 4% were resistant to ticarcillin. Intraperitoneal cefazolin/ceftazidime was initially used in 12 episodes (46%), and intraperitoneal cefazolin/aminoglycosides were used in another 12 episodes . Two patients (8%) were initially treated with intravenous vancomycin/ceftazidime for septic shock. Antibiotics were shifted to intravenous ceftazidime and intraperitoneal gentamicin in 1 patient and intraperitoneal ceftazidime/gentamicin in the other after the patients stabilised with fair responses.The antibiotic susceptibilities of the Acinetobacter. A primary response was achieved in 16 episodes (62%), and after antibiotics, a secondary response was obtained in another 7 episodes (27%). There was no difference between time groups regarding antibiotic response percentage. The average time to antibiotic switch was 4 days , and episodes that occurred after 2000 presented a significantly shorter time to antibiotic switch (P<0.01). Those responding to antibiotics were maintained on susceptible antibiotics for an average of 17 days . About half of the episodes (46%) required hospitalisation, with more patients in the after-2000 group admitted (P = 0.01) but no significant difference in hospitalisation duration. A total of 3 patients (12%) with PD-related peritonitis caused by Acinetobacter had technique failure with catheter removal. The overall outcome was fair. None of the patients with Acinetobacter PD-associated peritonitis developed relapse or repeat peritonitis, and there was no mortality from such peritonitis.Acinetobacter peritonitis episodes over more than 20 years, we found that A. baumannii was the most common species identified from the effluent, and the leading causes of infection were sterility break and GI microflora translocation. Nearly half required hospitalisation, but the outcome was good, with only 12% of technique failure and no mortality cases. In addition, temporal differences in the clinical features, including the interval between the last and current peritonitis episodes, increased significantly after 2000, along with more episodes from sterility break and less from exit site infection/tunnel infection. However, the fair outcome of Acinetobacter peritonitis surprisingly did not change with time.In the present study of Acinetobacter peritonitis, our patients (before 2000) were of similar age and carried a similar percentage of comorbidities  Compared with past reports of Acinetobacter species are strictly aerobic, pleomorphic, and non-motile GNB. To date, 26 named species and 9 genomic species have been identified, among which A. baumannii and Acinetobacter genomic species 3 and 13TU are collectively referred to as the A. baumannii complex Acinetobacter species, each with different epidemiologic and microbiologic features A. baumannii complex species are prone to develop antibiotic resistance and frequently cause nosocomial outbreaks through their persistent presence in health-care facilities. Second, A. iwoffii and A. johnsonii are antibiotic-susceptible skin commensal flora of animals and humans, mostly resulting in food spoilage. Finally, A. calcoaceticus and other Acinetobacter members are ubiquitous colonisers in soil and wastewater, with low virulence and high antibiotic sensitivity. In our PD peritonitis series, the predominant pathogen differed with time; A. iwoffii was the predominant offender before 2000 but was replaced by A. baumannii after 2000  to colonisers of health-care settings (A. baumannii). This transition might reflect the improvement of exchange systems and increased utilisation of health-care resources as time passed.ter 2000 . This seet al. proposed that Acinetobacter PD peritonitis often occurred during a “vulnerable period, when hosts were immunocompromised,” especially in the months immediately following another PD peritonitis episode Acinetobacter episodes was 4 to 5 months at that time , but more from the hygiene breaks and failure to perform sterile exchange procedures. This phenomenon could be reminiscent of the routes of staphylococci infections.Galvao hat time  [13], . hat time , the for sources  and 4. WAcinetobacter PD-associated peritonitis is contrary to what we might expect if extrapolating from the experiences of hospital-acquired Acinetobacter species infections Acinetobacter PD peritonitis, followed by aminoglycosides or fluoroquinolones. Empirical use of ceftazidime might carry a 10% to 30% risk for treatment failure.The choice of treatment for Acinetobacter peritonitis remained fair throughout the follow-up period, despite the increase in A. baumannii percentage. A. baumannii infections are reportedly associated with 10% to 20% higher attributable mortality and longer length of hospital stay A. baumannii PD-associated peritonitis is unusual. We proposed several reasons for this finding. First, the overall antibiotic resistance rate in our Acinetobacter effluent isolates is quite low (including A. baumannii), and this phenomenon holds true in other major PD peritonitis series as well (Acinetobacter isolates Acinetobacter infection than in the other types. Finally, as we explained, the origin of Acinetobacter PD peritonitis has gradually shifted from poor host immunity to sterility break. This might also play a role in the relatively fair outcome of Acinetobacter peritonitis.An interesting issue among our findings is that the outcomes of  as well  [8], [12Acinetobacter, with focused descriptions of their clinical features. The temporal changes in the characteristics of patients with Acinetobacter peritonitis include an increasing proportion of A. baumannii, more cases from breaks in exchange sterility, fewer cases from catheter infections, and an increasing interval between the previous and the present peritonitis episodes. These features might have important epidemiologic meanings in the PD field and warrant our continuous attention.To our knowledge, this study is the most up-to-date and comprehensive report of PD-associated peritonitis caused by


Journal of Intensive Care and sincerely welcome you to this new journal published by the Japanese Society of Intensive Care Medicine in collaboration with BioMed Central.I am honored to write this editorial for the launch of Textbook of Critical Care Medicine, the editors wrote that critical care is no longer a young specialty in medicine [Journal of Intensive Care, was needed to help further develop intensive care medicine worldwide.In the preface of the fourth edition of medicine . A decadmedicine . A largemedicine  wrote thJournal of Intensive Care is an open-access, peer-reviewed online journal that encompasses all aspects of intensive care and acute medicine. The journal aims to publish articles contributing to the development of intensive care medical science and also encourages submissions considering the different cultural aspects of intensive care practice. Open access means that all articles accepted after peer review are freely and universally accessible online via the journal website, PubMed Central [Journal of Intensive Care has the potential to reach a much larger set of readers than any subscription-based journal, whether in print or online [Critical Care Medicine, it was announced that the journal has decided to decrease the number of print pages and publish some articles online only [Journal of Intensive Care on route for great success in the future. As commitment to the journal as it begins to establish itself with researchers, the Japanese Society of Intensive Care Medicine has waived the fee which is usually associated when publishing in an open-access journal. Central , and othr online . Anotherine only . This, aJournal of Intensive Care depends on the articles published and so urge you to submit your manuscripts to us. We also believe in the importance of providing a fair and quick peer-review process for our authors. The journal operates a traditional closed peer-review model, and a minimum of two reviewers are consulted for each submission that proceeds to peer review. Peer review is conducted by our experienced Editorial Board members, all of whom adhere to Journal of Intensive Care's editorial policy of offering a rapid, high-quality peer-review service. We continuously aim to improve the journal standing in the field by both publishing high-quality articles and providing constructive peer-review processes.We believe that the reputation of Journal of Intensive Care to the world.We have been editing a lot of manuscripts since we started accepting submissions a few months ago and are pleased to see submissions from not only Japan but also the Pan-Pacific countries as well as all from further afield. We have worked very hard in getting the journal ready to launch, and following this editorial, you will find the first articles to be published. We are really proud of showcasing these articles and


There are errors in affiliation 2 and affiliation 3 for author Abdelali Haoudi. Affiliation 2 should be: King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, National Guards Health Affairs, Riyadh, KSA. Affiliation 3 should be: Department of Genetics and Genomics, Boston Children’s Hospital, Harvard Medical School, USA.


International Journal of Qualitative Studies on Health and Well-being's thematic cluster on Health, Physical Activity and Lifestyle, it is our privilege to introduce the theme and six original articles included in the cluster. The papers address some central aspects of the theme  from psychological, sociological, pedagogical, medical, and also interdisciplinary perspectives through implementation of different qualitative research approaches  and designs . The author team is internationally representing Sweden, Denmark, and the United Kingdom. Two review papers open the cluster and are followed by four research papers.As guest editors of the Physical activity, or the lack of it, is a major public health issue in many countries. The World Health Organization (WHO) has reported that physical inactivity is one of the ten leading causes of death in developed countries resulting in about 1.9 million preventable deaths worldwide annually WHO, . ConsideInternational  paper, Staveborg Kerkelä, Jonsson, Lindwall, and Strand  provide In the fourth paper, Lindqvist, Kostenius, Gard, and Rutberg  exploredIn the fifth (single case study) paper, Stelter  shared hIn the sixth (research) paper, Papathomas, Williams, and Smith  used narInternational Journal of Qualitative Studies on Health and Well-being and attract more researchers in the sport/exercise sciences to contribute to the journal in future.Finally, as guest editors we wholeheartedly thank the authors for their tireless efforts in creating interesting and high-quality contributions, and all the reviewers for their constructive comments that contributed to raise the scientific quality of the thematic cluster. Our deep thanks also go the editors of the journal and the publisher, for smooth cooperation during the preparation process. We do hope that this thematic cluster will contribute to expanding the scope of the Urban Johnson Sport and Exercise Psychology School of Health and Welfare Halmstad University, Halmstad, Sweden E-mail: urban.johnson@hh.sNatalia Stambulova School of Health and Welfare Halmstad University Halmstad, Sweden


PML-RARA fusion due to a translocation t. Its sensitivity to treatment with all-trans retinoic acid (ATRA), which causes differentiation of the abnormal promyelocytes, combined with anthracycline based chemotherapy makes it the best curable subtype of acute myeloid leukemia. A rapid and accurate diagnosis is needed in the first place to prevent (more) bleeding problems. Here we present a patient with a leukemia with an APL-like morphology but no detectable PML-RARA fusion, as demonstrated by RT-PCR and cytogenetic analysis.Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by a MYC-region showed the presence of multiple MYC amplicons. SNP-array analysis uncovered amplification of the 8q24.13-q24.21 region, including the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same chromosome region.Unexpectedly, karyotyping revealed numerous double minutes (dmins). Fluorescence in situ hybridization (FISH) with DNA probes specific for the The diagnosis was revised to AML, not otherwise specified  and therefore therapy with ATRA was discontinued. Acute promyelocytic leukemia (APL) is a hematological emergency frequently associated with severe coagulation disturbances. The typical morphology shows abnormal, usually bilobed hypergranular promyelocytes. In some cases the cytoplasmic granules are so large or numerous that they completely fill the cell, obscuring the nuclear cytoplasmic limit. Frequently characteristic cells containing bundles of Auer rods, the so-called faggot cells, are seen. In APL, Sudan Black (SB) or myeloperoxidase (MPO) is always strongly positive in all blast cells, with the reaction product covering the whole cytoplasm and often the nucleus too .RARA) gene usually on 17q21 , RP11-495D4 , RP11-367L7 , RP1-80K22 , RP11-125A17 , RP11-316E19  and RP11-268C19  from BlueGnome Ltd, Cambridge, UK.PML-RARa fusion transcripts were amplified using RT-PCR according to Miller et al. .arr 8q24.13x1,8q24.13q24.21 amp,8q24.21q24.22x1,9p21.3x1,9p21.3x0,9p21.3x1.9/l. Based on the additional investigations the diagnosis of APL was altered to AML, not otherwise specified  [Following leukapheresis and administration of daunorubicin leucocyte counts dropped to 0.9 10ML, NOS) .The patient’s age and physical condition didn’t allow to deliver intensive anti-leukemic chemotherapy. He subsequently developed a paralytic ileus and hypotension and died.PML-RARA fusion product present. In fact, cytogenetic analyses showed no t, but the presence of 7 to 50 double minutes (dmins). SNP-array identified a 4,56 Mb large amplicon (containing 15 genes), flanked by a proximal deletion of 693 kb (10 genes) and a distal deletion of approximately 1,07 Mb (6 genes), as well as a homozygous deletion in 9p21.3 of 443 kb (4 genes), which was flanked by two heterozygous deletions: one distal deletion of about 1,4 Mb (25 genes) and one proximal deletion of 443 kb (2 genes), see Table In this report we describe a patient with a rare APL-like phenotype. At presentation the peripheral blood smears showed a typical APL morphology. However, immunophenotyping results were not typical for APL, that is usually HLADR negative with homogeneous expression of CD33 and CLIP positive . Moreoveowed no t5;17, butMYC-gene is involved in this amplification and can be present as dmins or homogeneously staining regions (hsr). Gene amplification in AML is rare, the most frequent gene involved being MYC and the second most common oncogene MLL [MYC amplification manifesting as dmins has been described in only a few cases with an APL or APL-like morphology [Amplification of human chromosome region 8q24 has been associated with many types of solid tumors, such as breast, prostate, colon, lung, ovaries and pancreas -11. The gene MLL , mostly rphology -15.In solid tumors, such as colon, pancreatic and breast carcinomas, brain tumors and neuroblastomas, dmins can be observed as a late genomic event in tumorigenesis, the dmins being associated with a rapid cellular growth and poor prognosis. In AML dmins appear less frequently, in about 1% of the cases ,16,17. TThe deletion in 8q was larger than the amplified segment in dmins, and this phenomenon was also observed in a study by Storlazzi et al. , who desMYC from 8q24 with subsequent amplification of this region into dmins may have led to upregulation of the expression of the MYC oncogene, a known critical nuclear transcription factor.The first patient with MYC amplification in dmins as the sole cytogenetic aberration has been described by Frater et al. . Also inPML-RARA fusion presented by Bruyère et al. [MYC amplification as dmins and an apparently terminal deletion of the short arm of chromosome 9 with the breakpoint at band p21. Our findings support their suggestion that there might be an association between loss of 9p, dmins, and an APL-like morphology.Deletions of 9p are not frequent recurrent chromosome aberrations in AML. Usvasalo et al.  reportede et al.  showed MPML-RARA fusion but MYC amplification in dmins. It is of utmost importance to have a rapid confirmation or exclusion of t in an acute leukemia that morphologically resembles APL. Therefore, in our routine practice we have implemented a rapid, four hours interphase FISH test using a LSI PML/RARA DC DF Probe (Vysis) on bone marrow or blood smears from patients suspected for APL. In contrast to the other similar reported case [In summary, we describe a patient with an APL-like morphology, who showed no sion of t;17 in anInformed consent was obtained from the patient for the publication of this report and any accompanying images.


Aggressive chondroblastoma of the distal tibia is rare, and below-knee amputation had been the standard surgical procedure.We reported an additional case and reviewed the existing literature. A 20-year-old man with a 2-month history of right ankle pain and swelling underwent distal tibia wide resection, double pedicle fibular, autogenous iliac bone graft, and ankle arthrodesis. He had no pain, no limitation in daily activities, and no evidence of local recurrence and infection; the Musculoskeletal Tumour Society Score (MSTS) is 86 % at the final follow-up.Double pedicel fibular graft and ankle arthrodesis may be an effective and economical alternative method for aggressive chondroblastoma in the distal tibia.The online version of this article (doi:10.1186/s12957-016-0839-z) contains supplementary material, which is available to authorized users. Chondroblastoma of bone, considered a benign lesion, is an uncommon condition that has a predilection for secondary ossification centers, particularly of the proximal humeral, tibia, and distal femur . It occuAggressive chondroblastoma of the distal tibia is further rare. For patients with aggressive chondroblastoma, treatments including below-knee amputation and arthrodesis have been recommended. With the development of limb salvage techniques, arthrodesis is becoming preferred. Among the options of arthrodesis, vascularized free fibular and non-vascularized autogenous fibular grafts were regarded as the most chosen reconstruction according to situations. In this report, we describe the successful wide resection of aggressive chondroblastoma and reconstruction with double pedicel fibular graft and ankle arthrodesis.In April 2010, a 20-year-old man with a 2-month history of right ankle pain and swelling presented in our hospital. His medical history was otherwise unremarkable. On physical examination, there was a mass with associated tenderness at the posterolateral aspect of the distal tibia. There was 18° restriction of plantar flexion and a 5° restriction of dorsiflexion. Plain radiograph and CT showed lytic lesions on posterolateral aspects of the distal tibia, and it appears as an ovoid lesion located centrally in the epiphysis Figs. . An inciPosterolateral incisions were taken according to the site of biopsy and the position of the tumor. During the decomposition, the superficial peroneal nerve was identified and was retracted laterally. The flexor muscle of the thumb was exposed from peroneal muscle gap, and the muscle fibers were cut to the flexor muscle of the thumb, and, the remaining fibula periosteum and some muscle fibers were separated in the fibula. In the separation process, resection of the distal fibular of 12 cm in length should be performed and proximal vascular ligation should be also retained to form a distal pedicel fibula bone flap and peroneal artery including its branch vessels.0–100 valgus, 100 external rotation, and a neutral dorsiflexion. An autogenous iliac bone graft was also inserted to fill the remaining defect in the tibia and recipient bed of the talus (Fig. After opening the extensor retinaculum, the joint capsule was exposed and meticulous dissection was carried out to preserve a wide protective margin of the tissue. Previous biopsy tracts were incorporated into the incision and completely excised with the specimen. According to the tumor position determined by CT, the posterolateral and central parts of the distal tibia were resected from 1 cm proximal along with the tumor remaining medial part. The soft tissue protruded by the tumor was also wide resected. After the fibula periosteum and the muscle fibers were separated at the fibular head, the fibula head was resected to maintain long enough pedicel and articular cartilage of the talus and medial ankle were eradicated while preparing two holes in the talus head. After distal fibular was folded up into two, the two pedicel graft were inserted between the medullary canal of the tibia and the holes in the talus. Then, a titanium plate between the distal tibia and talus was fixed. Attention should be taken to place the ankle in 5lus Fig. .Fig. 5PoSince chondroblastoma is a benign lesion wholly, curettage and osteoplasty using auto- and homograft are the main method for chondroblastoma in most cases and additional implants may be used if there is mechanical instability. For particularly aggressive tumors, marginal or wide resection is necessary. In exceptional cases, amputation may be necessary when the soft tissue and neurovascular bundle are extensively involved .Tumors of the distal tibia are quite rare. For malignant and potential malignant tumors, below-knee amputation had been the standard surgical procedure  because We used a plate and a screw as the fixation device in this patient because of enough soft tissue. This procedure was also simpler than intramedullary nailing suggested by Moore’s series for shortage of the soft tissue. In our experience, wide resection and reconstruction with double pedicel fibular graft and ankle arthrodesis is a valuable alternative in limb salvage for aggressive chondroblastoma in the distal tibia. This technique avoids the donor site morbidity of auto-graft used, the talus collapse and bone loss associated with an ankle endoprosthesis. After ankle arthrodesis, our patient had 20° of tibiopedal motion Fig.  and no cDegenerative arthrosis may develop in the sub-talus joint after ankle arthrodesis . throughWe describe a novel technique of double pedicel fibular graft and ankle arthrodesis for aggressive chondroblastoma in the distal tibia. This technique allowed for retention of protective motor function and avoidance of ankle immobilization, while providing no pain, no limitation in daily activities, and no evidence of local recurrence and infection, 86 % of MSTS score, and patient satisfaction compared with traditional below-knee prosthesis after amputation.Written informed consent was obtained from the patient for publication of this manuscript and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Achromobacter xylosoxidans ADAF13, isolated from farmland soil, possesses a large number of putative degradation genes and pathways that break down a wide variety of aromatic hydrocarbons, pesticides, endocrine disruptors, and other high-impact xenobiotics. These properties make this strain an excellent candidate for further development as a broad-spectrum bioremediation agent. Achromobacter xylosoxidans ADAF13 is a Gram-negative, oxidase- and catalase-positive bacterium from the genus Achromobacter. A. xylosoxidans is well known for its opportunistic pathogenicity and infection of pulmonary tissue in immunocompromised individuals. These infections are particularly common in cystic fibrosis patients  and filtered using BBTools (https://sourceforge.net/projects/bbmap/), with a minimum Phred score of 20. Paired-end reads were assembled into 120 contigs with the SPAdes 3.6.2 program (de novo annotation was performed with Prokka (http://www.ncbi.nlm.nih.gov/genomes/static/Pipeline.html). The metabolic pathways of aromatic and heterocyclic compounds were examined using the KEGG databases (cticides . In compatabases . ADAF13 A. xylosoxidans ADAF13 whole-genome shotgun (WGS) project has the project accession no. LSMI00000000. This version of the project (01) has the accession no. LSMI01000000 and consists of sequences LSMI01000001 to LSMI01000120.The


Pancreas transplantation has emerged as an effective treatment for patients with diabetes mellitus, especially those with established end-stage renal disease. Surgical and immunosuppressive advances have significantly improved allograft survival. The procedure reduces mortality compared with diabetic kidney transplant recipients and wait listed patients. Improvements in diabetic nephropathy and retinopathy have also been demonstrated. Pancreas transplantation can improve cardiovascular risk profiles, improve cardiac function and decrease cardiovascular events. Lastly, improvements in diabetic neuropathy and quality of life can result from pancreas transplantation. Pancreas transplantation remains the most effective method to establish durable euglycemia for patients with diabetes mellitus. Diabetes mellitus afflicts about 6% of the general population; it is currently the third most common disease and the fourth leading cause of death by disease in the United States. Of the estimated 21 million diabetic individuals in the United States, 1 to 2 million has insulin-dependent diabetes mellitus (IDDM). Nearly 300,000 new cases of IDDM are diagnosed each year, and the incidence is increasing [1]. Pancreas transplantation has assumed an increasingly important role in the treatment of IDDM. It is currently the only available treatment that reliably provides an insulin-independent state, resulting in euglycemia and normal glycosylated hemoglobin levels by re-establishing endogenous insulin secretion responsive to normal feedback controls  transplant), where the kidney graft is obtained from either a living or deceased donor. The usual indication for this procedure at most centers is a type 1 diabetes patient with ESRD.Simultaneous Pancreas-Kidney (SPK) Transplantation In SPK transplantation, the pancreas and kidney are usually obtained from the same deceased donor. Therefore, changes in kidney function can be used to determine whether rejection is occurring in either organ -6.Pancreas-after-Kidney (PAK) Transplantation This is the second most common pancreas transplant procedure. The indication for this procedure is a patient with type 1 diabetes who has identified a living donor for kidney transplant and wants to plan a later PAK transplant, or the type 1 diabetes patient who already has a kidney transplant that has stable graft function, desires the potential benefits of euglycemia, and has the cardiac reserve to undergo the procedure -7.Pancreas Transplant Alone (PTA) Pancreas transplant alone is the least common pancreas transplant procedure performed. Frequent, severe, hypoglycemic events are the most common indication for this procedure. The American Diabetes Association position statement suggests that indications for pancreas transplant (in the absence of kidney failure) are “frequent, acute and severe metabolic complications  requiring medical attention” as well as “clinical and emotional problems with exogenous insulin therapy that are so severe as to be incapacitating; and consistent failure of insulin-based management to prevent acute complications” .SURGICAL ISSUES IN PANCREAS TRANSPLANTATIONBladder vs. Enteric Duct Management With bladder drainage (BD), urine amylase can be used as a marker of graft function. Biopsies of the pancreas graft are also easily obtained across the bladder wall through cystoscopy. However, this procedure also creates potential complications. Metabolic acidosis occurs in most cases, and extracellular volume depletion is common, occasionally severe enough to require hospitalization; both complications are due to the loss of sodium bicarbonate-rich pancreatic secretions into the urine. Additional problems that can complicate BD include bladder leak, reflux pancreatitis, particularly with neurogenic bladder, chemical cystitis/urethritis, and frequent bladder infections, duodenitis in the connecting segment, bladder tumors, bladder calculi, urethral stricture, urethral erosion, epididymitis, prostatitis, and prostatic abscess. The frequency of urological complications is high (50%–77%), but they rarely result in graft or patient loss.The alternative to BD is enteric drainage (ED) of the exocrine duct. In this procedure, the pancreatic duct is inserted into the small bowel using a small “button” of duodenum or with a Roux-en-Y limb. There is less need for monitoring the pancreas graft, overall, because immunosuppression has improved and frequency of rejection episodes has decreased after pancreas transplant of all types. Indications for enteric conversion surgery (20%–25%) are frequent episodes of severe extracellular volume depletion, severe metabolic acidosis, urological complications, or problems with the duodenal segment.SPK transplants performed with either BD or ED have equal pancreas graft survival.Portal vs. Systemic Venous Drainage When placed in the systemic circulation—called systemic venous drainage (SVD)—the insulin secreted into the pancreatic venous effluent is not extracted immediately by the liver, as it would be if it emptied into the portal circulation. Systemic concentrations of insulin, both fasting and postprandial, are elevated as a result. Subsequently, a procedure was developed where the graft was placed in the portal circulation and the pancreatic duct was drained into the small intestine. This combined portal venous drainage (PVD) with ED procedure resulted in much lower peripheral insulin concentrations than pancreas transplant recipients with SVD, comparable to nondiabetic kidney transplants receiving similar immunosuppression.COMPLICATIONSThe complexity of the whole pancreas transplant procedure, along with the likelihood of pre-existing disease secondary to their diabetes, exposes the recipient to a variety of significant operative and post-operative risks. The extent of the post-operative problems likely limited the widespread acceptance of pancreas transplantation in the early era of its development. Serious surgical complications following the procedure include thrombosis of graft vessels, intra-abdominal hemorrhage, anastomotic leak (enteric or bladder), graft pancreatitis, pancreatic fistula formation and intra-abdominal sepsis, all of which may require re-laparotomy and the possibility of graft loss. In recent years, with improvements in donor and recipient selection criteria, surgical technique, immunosuppression protocols (reduced incidence of early and acute rejection), and prophylaxis regimes , there has been a significant decrease in the overall incidence of serious complications and the rate of re-laparotomy.IMMUNOSUPPRESSIONThe most common regimen in all pancreas transplant categories in 2000 was tacrolimus/mycophenolate mofetil  with cyclosporine/MMF a distant second (5%–20%) . The comMany centers still use corticosteroids in their immunosuppression protocol, which may allow a reduced dose of calcineurin inhibitor, but others have tried to move to a “steroid-free” protocol with the assumption that this will decrease risk of weight gain, glucose intolerance, dyslipidemia, and bone loss.The results of clinical pancreas transplantation continue to improve as immunosuppressive strategies become more targeted. Although corticosteroid withdrawal or avoidance is a clinical reality, particularly in SPK and PAK recipients, CNI minimization or elimination remains a work in progress. Induction immunosuppression is routinely used in whole pancreas transplantation, with >75% of recipients receiving either 1) a T-cell depleting polyclonal antibody  or monoclonal antibody ; 2) a non-depleting monoclonal anti-CD25 antibody ; or 3) both. The initial results with alemtuzumab induction appear quite promising, although it appears to be more effective when used as a conventional induction agent rather than a tolerance-inducing or maintenance immunosuppressant. In SPK recipients, both T-cell depleting and non-depleting antibody agents for induction have been used, whereas in solitary PTX, the use of T-cell depleting antibodies has been greater. Monotherapy can be achieved in a proportion of patients, but it remains unclear which regimen is most effective and safe. Future clinical studies will continue to focus on long-term outcomes, appropriate donor and recipient selection, immunologic monitoring, immunosuppressive reduction, and outcomes-based research.RESULTS AND OUTCOMEWhole-organ SPK transplant with normal graft function consistently improves 7- to 10-year patient survival compared with deceased donor kidney transplant, SPK transplant with loss of pancreas graft function, or dialysis in type 1 diabetic patients waiting for a transplant .Patient survival after SPK transplant is consistently better than that observed after cadaveric-donor kidney transplant, with the possible exception of recipients over age 50. Although this advantage may, in part, be due to improved glucose after SPK transplant compared with kidney transplant alone, differences between the recipients who undergo these procedures, and between the donor grafts used for these two procedures, would likely also contribute to the difference in survival described between these two procedures. Mortality after SPK transplant is equal to living-donor kidney transplant alone after 10 years, and both PAK and pancreas transplant alone may increase 4-year mortality compared with remaining on the waiting list for those procedures. In these cases, specific quality of life (QOL) concerns and impact of pancreas transplant on specific diabetic complications need to be weighed against potential early increase in mortality before these procedures are considered.Whole pancreas transplantation has proven to be a safe procedure with a 1- and 3-year patient survival rates for all forms of pancreas transplant  in the US since 1998 at almost 95%, and 89%, respectively  [Serum glucose level normalizes immediately after pancreas transplant, at the expense of hyperinsulinemia if SVD is used. Insulin secretion demonstrates oscillations despite denervation, as well as normal first- and second-phase secretion responses, unless there is a decrease in graft function or increased insulin resistance. C peptide concentrations are often slightly elevated, both basally and after mixed meal stimulus, but similar to those of non-diabetic kidney transplant recipients. Although fasting proinsulin is increased, it does not necessarily represent failing graft function, and glucagon response to hypoglycemia improves over time. Glucagon and symptom response to hypoglycemia return to normal or near normal over time; epinephrine and growth hormone responses though improve do not become normal after pancreas transplant. Hypoglycemic symptoms and documented events are uncommon and tend to diminish over time but may be due to a variety of factors. It should be cautioned that glucagon secretion in response to hypoglycemia does not improve with either allo- or auto-transplantation of islets into the liver, in human or animal studies, as described with pancreas transplant, and may be related to their location in the liver .Diabetic nephropathy can be prevented by a functioning pancreas graft, and pathological changes of diabetes can reverse over time after more than five years of normal pancreas function . DiabetiThe most common cause of death in diabetes and transplant patients is vascular disease. Improved glucose control, as with SPK transplant, can improve vascular reactivity and microvascular integrity and responses, but other factors after transplant may prevent or minimize these improvements in some patients . ChangesISLET CELL TRANSPLANTATIONIslet cell transplantation is an attractive alternative therapy to conventional insulin treatment or vascularized whole pancreas transplantation for type 1 diabetic patients by islet cells isolation from donor pancreata and embolization into the recipient liver via the portal vein. Compared to pancreas transplantation, islet cell transplantation is technically much simpler , has lower morbidity and offers the opportunity for storage of the islet graft in tissue culture or cryopreservation for banking -15.With recent advances in methods of islet isolation and the introduction of more potent and less diabetogenic immunosuppressive therapies, islet cell transplantation has progressed from bench to clinical reality. Presently, several international centres have demonstrated successful clinical outcomes with high rates of insulin independence after islet transplantation . OngoingOver the past few years, there has been tremendous progress in clinical islet transplantation, from refinements of the Edmonton Protocol to novel strategies for improved islet isolation, implantation and recipient immunosuppression. One of the most critical areas of research is the islet isolation procedure, which remains highly labor intensive, expensive and relatively inconsistent. Even the highest grade preparations only recover about 20%–50% of the potential islet mass. Moreover, rates for successful islet isolation at leading centers vary from 25% to 75%, depending largely on the quality of the pancreas, the amount of cold storage and the heterogeneity of collagenase preparations -15.As islet transplantation moves forward, one of the first challenges is to reliably achieve insulin independence with single-donor grafts. Based on experience with islet auto-transplantation after total pancreatectomy, a minimum of 300,000 islets are necessary to achieve insulin independence in 70% of recipients . This isDevelopment of novel immunosuppressive protocols using more specific and less toxic drugs, ultimately towards inducing tolerance, is an important step in applying islet transplantation earlier in the course of the disease, including transplantation in children. Moreover, advances in identifying other sources of islet cells, together with progress in better understanding the biology of diabetes, will help increase the limited supply of islets through gene therapy, stem-cell biology techniques or xenotransplantation. It is anticipated that continued international collaboration will further stimulate excitement in the field, as innovative solutions are created to meet the remarkable challenges that lie ahead.


International Journal of Telerehabilitation (IJT) contains original research that analyzes provider perspectives on the use of telepractice to serve the families of children who are deaf or hard of hearing. Two case studies examine the utility of administering Facial Affect Training through telepractice to individuals with chronic traumatic brain injury. An article in IJT’s policy section describes the process for the formulation of the World Federation of Occupational Therapists (WFOT) international telehealth position statement for occupational therapy. The World Federation of Occupational Therapists (WFOT) consists of 84 member organizations representing over 420,000 occupational therapists internationally . The Spring 2015 issue also contains announcements of upcoming conferences. As of May 2015, the International Journal of Telerehabilitation (IJT) is live on PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/journals/2411/. Articles from all past issues were indexed, as will be the current and future issues.The Spring 2015 issue of the  International Journal of Telerehabilitation (IJT) contains a mix of research, clinical case studies, an article that documents the genesis of the World Federation of Occupational Therapists’ (WFOT) International Telehealth Position Statement for Occupational Therapy, and announcements of major association sponsored meetings.The Spring 2015 issue of the In this issue, Behl and Kahn shared provider perspectives on the provision of telepractice to families of children who are deaf or hard of hearing. Williamson and Isaki presented two case studies on the novel use of Facial Affect Training through telepractice to individuals with chronic traumatic brain injury. Jacobs et al. reported upon the process for the formulation of the World Federation of Occupational Therapists (WFOT) International Telehealth Position Statement for Occupational Therapy. The World Federation of Occupational Therapists (WFOT) consists of 84 member organizations representing over 420,000 occupational therapists internationally . This policy statement was previously published in IJT.http://www.ncbi.nlm.nih.gov/pmc/journals/2411/. Articles from all past issues are now indexed, as will be the current and future issues.In May 2015, the International Journal of Telerehabilitation (IJT) became live on PubMed Central: We welcome two new additions to the IJT editorial team: Sections Editor William E. Janes, OTD, MSCI, OTR/L and Layout Editor Erin M. Clephas and thank them for their service.ecohn@pitt.edu) or Senior Associate Editor Jana Cason  if you are interested in contributing to a future issue.The next volume of the International Journal of Telerehabilitation will be published in late Fall, 2015. We cordially invite your submissions by September 1, 2015. IJT accepts original research, case studies, viewpoints, technology reviews, book reviews, and country reports that detail the current status of telerehabilitation. Our peer reviewers constitute a multi-disciplinary group, and include researchers and clinicians from each of the major rehabilitation disciplines, rehabilitation engineers, health information managers, information technologists, and others. We welcome new peer-reviewers and invite guest editors with ideas for special, thematically focused issues. The IJT publication team is agile and can add additional issues as warranted to ensure currency. Please contact Editor Ellen Cohn, PhD (Respectfully,Ellen R. Cohn, PhD, CCC-SLPIJT EditorJana Cason, DHS, OTR/L, FAOTAIssue Co-Editor and IJT Senior Associate Editor


Biological Procedures Online warmly thank the 30 reviewers whose comments helped to shape the journal, for their invaluable assistance with review of manuscripts in Volume 17 (2015).A peer-reviewed journal would not survive without the generous time and insightful comments of the reviewers, whose efforts often go unrecognized. Although final decisions are always editorial, they are greatly facilitated by the deeper technical knowledge, scientific insights, understanding of social consequences, and passion that reviewers bring to our deliberations. For these reasons, the Editor-in-Chief and staff of  Ergul Belge KurutasTurkeyShantanu BhattUSAXiaolei ChenUSAWim D'HaezeUSASofia DuartePortugalChristine EbelFranceDavid GewirtzUSAEduardo GilglioniBrazilBrenda Gonzalez-HernandezMexicoS Kavimani KavimaniIndiaSandro KellerGermanyYan LuoUSAGeorge McNamaraUSASang MeixiangUSAMeral MiralogluTurkeyTapan MohantaKorea, Republic ofCraig NunemakerUSAToshifumi OzakiJapanSatyabrata PanyUSAM D ShahjahanBangladeshRobert SilvermanUSAJames SturgisFranceMasatoshi TagawaJapanRoger Y TsienUSALiyang WangChinaWei XiaweiChinaXuehong XuChinaShaomian YaoUSASwee Keong YeapMalaysiaYing YuChina