International Journal of Environmental Research and Public Health [The authors wish to make the following corrections to their paper published in the c Health : Bacillus thuringiensis var. israelensis (Bti) , CG formulation).” should read “Larviciding was done with a granular formulation (VectoBac® CG) of the bacterial larvicide (BL) Bacillus thuringiensis var. israelensis (Bti) strain AM65-52, Valent BioSciences Corporation ”.Page 5326, line 24, the sentence “Larviciding was done with the microbial agent of bacterial pathogens The authors would like to apologize for any inconvenience caused to readers by these changes.


Knowledge discovery in bioinformatics thrives on joint and inclusive efforts of stakeholders. Similarly, knowledge dissemination is expected to be more effective and scalable through joint efforts. Therefore, the International Conference on Bioinformatics (InCoB) and the International Conference on Genome Informatics (GIW) were organized as a joint conference for the first time in 13 years of coexistence. The Asia-Pacific Bioinformatics Network (APBioNet) and the Japanese Society for Bioinformatics (JSBi) collaborated to host GIW/InCoB2015 in Tokyo, September 9-11, 2015. The joint endeavour yielded 51 research articles published in seven journals, 78 poster and 89 oral presentations, showcasing bioinformatics research in the Asia-Pacific region. Encouraged by the results and reduced organizational overheads, APBioNet will collaborate with other bioinformatics societies in organizing co-located bioinformatics research and training meetings in the future. InCoB2016 will be hosted in Singapore, September 21-23, 2016. For the first time the 26th International Conference on Genome Informatics (GIW) and the 14th International Conference on Bioinformatics (InCoB) were jointly held in Tokyo, September 9-11, 2015 [GIW/InCoB2015 offered authors of original research papers a choice of seven journal tracks for submission: BMC Genomics, BMC Bioinformatics, BMC Systems Biology, BMC Medical Genomics, Bioinformatics, IEEE/ACM Transactions on Computational Biology, Bioinformatics, and the Journal of Bioinformatics and Computational Biology. Of 106 manuscript submissions, 51 (48%) were accepted after a cycle of peer reviews and one or two revisions by at least two members of the 110 members of the Program Committee and 39 external sub-reviewers  is involved in neuronal plasticity . Dutta eet al.  used itset al. [Membrane transporters are in important class of proteins in drug target design. Since the number of resolved 3D structures is limited the high accuracy prediction of membrane transporters from primary sequence data is of considerable interest. Liou et al.  applied et al. [® an algorithm for the improved peak detection and parameter estimation to increase the accuracy of molecule identification.Low resolution mass spectrometry data derived from metabolome or proteome studies often show overlapping peak distributions. Wijetunge et al.  implemenJoint or co-located meetings offer participants a diverse program at lower cost than separate events and provide a unique networking opportunity. Therefore, InCoB will partner different stakeholders in the bioinformatics community in the future. InCoB2016  will be AIST - National Institute of Advanced Industrial Science and Technology, JapanAPBioNet- Asia-Pacific Bioinformatics NetworkIEEE/ACM IEEE Communications Society/Association for Computing MachineryGIW - International Conference on Genome InformaticsGOBLET - Global Organisation for Bioinformatics Learning, Education and TrainingHMM - Hidden Markov ModelInCoB - International Conference on BioinformaticsJSBi - Japanese Society for BioinformaticsTF - transcription factorThe authors declare that they have no competing interests.CS and SR wrote the introduction. CS and SMY (Program Committee Co-chairs) managed the review, revision and decision processes. TWT, PH and SR supported the post-acceptance and editorial processing, respectively. All authors have read and approved the final manuscript.List of GIW/InCoB2015 Reviewers. (*.pdf)Click here for fileGIW/InCoB2015 Best Paper Awards. (*.pdf)Click here for file


Thrombosis Journal would like to thank all our reviewerswho have contributed to the journal in Volume 11 (2013).The Editors of  Walter AgenoItalyTatsuya AtsumiJapanFidelia Bode-ThomasNigeriaAnnemieke BoumanNetherlandsSigrid BrækkanNorwayKaren BreenUnited KingdomAllison BurnettUnited States of AmericaAnthonius De BoerNetherlandsBas de LaatNetherlandsPieter EijgenraamNetherlandsEmmanuel FavaloroAustraliaHabib GamraTunisiaEsteban GandaraCanadaHadi GoubranEgyptAndreas GreinacherGermanyJob HarenbergGermanyCoenraad HemkerNetherlandsYvonne HenskensNetherlandsShawn HoffmanCanadaHisanori HoriuchiJapanAkira IshiguroJapanManuela JooreNetherlandsMakoto KanekoJapanAbdul Nafey KaziPakistanMarie-Claire KleinegrisNetherlandsTomohiro KogaJapanLai Heng LeeSingaporeMasahiro LekoJapanRinske LoeffenNetherlandsHelen ManiGermanyJun MimuroJapanToshiyuki MiyataJapanBaheramsjah MochtarNetherlandsManuel MonrealSpainEriko MorishitaJapanShosaku NomuraJapanRene Oerle vanNetherlandsMartin O'FlahertyUnited KingdomShouichi OhgaJapanTsukasa OhmoriJapanPaolo PrandoniItalyAvi RivkindIsraelChanggeng RuanChinaMeyer Michel SamamaUnited KingdomBob SiegerinkNetherlandsSonja SorensenUnited States of AmericaKatsue Suzuki-InoueJapanArina ten Cate-HoekNetherlandsArmando TripodiItalyGabriele VetschSwitzerlandAlejandro VidelaArgentinaJeanine WalengaUnited States of AmericaKristien WinckersNetherlandsYi WuChinaNorikazu YamadaJapanKazuma YamakawaJapanMasako YamazakiJapanTong YinChina


Pseudorhabdosynochus regius n. sp. is described from the gills of the mottled grouper Mycteroperca rubra caught off Senegal, Tunisia and Libya . The species is distinguished from its congeners by the structure of its sclerotised vagina (length 26–35 μm), which exhibits a trumpet in continuity with the primary canal, a straight primary canal, and primary and secondary chambers included in a common sclerotised mass along the primary canal. The species is also characterised by small squamodiscs (length 20–40 μm) with 10–11 rows of rodlets. Its closest relatives (based on the structure of the sclerotised vagina) are species mostly found in the Mediterranean Sea and parasites on species of Mycteroperca. A second species of Pseudorhabdosynochus Yamaguti, 1958 is reported from the same host and localities but not described. A list of diplectanids from groupers in the Mediterranean Sea is provided. We point out that a recent article was not compliant with the new Article 8.5.3 of the International Code of Zoological Nomenclature; for this reason, three species, P. nhatrangensis Dang, Bristow, Schander & Berland, 2013, P. vietnamensis Dang et al., 2013 and P. brunei Dang et al., 2013, are invalid. Mycteroperca rubra inhabits a rocky environment in the Mediterranean Sea and along the coast of the Eastern Atlantic Ocean  and contain evidence in the work itself that such registration has occurred [8.5.3. be registered in the occurred .”The recent amendment , 12 of tPseudorhabdosynochus from groupers of Vietnam were published in 2013 [International Journal of Aquatic Sciences. The website of this journal  claims that it is an electronic publication  and no mention of a printed version appears on the website or on the papers themselves. Therefore, the nomenclatural validity of the species described in this journal depends upon compliance with Article 8.5 of the Code, reproduced above. Articles 8.5.1 (after 2011) and 8.5.2  are satisfied. However, Article 8.5.3 is not satisfied: there is no mention of a ZooBank number associated with this work. Article 8.5.3.3. describes the cases in which an error can be admitted: “An error in stating the evidence of registration does not make a work unavailable, provided that the work can be unambiguously associated with a record created in the Official Register of Zoological Nomenclaturebefore the work was published” (the emboldened “before” is our own). We checked (2 December 2014) and found that neither these species nor the paper is indexed in ZooBank. According to the examples illustrating Article 8.5.3.3., even if the registration in ZooBank was performed now or later, the work would be unavailable.The descriptions of three new species of  in 2013 . The paphttp://www.worldcat.org/). Although these details do not specifically concern the case of the species dealt with in the present work, they show, more generally, that the journal itself  could not publish a valid species according to the new ICZN Article 8.5.Furthermore, to have its paper registered in ZooBank, the journal needs to meet the criteria enumerated in Articles 8.5.3.1 and 8.5.3.2. Article 8.5.3.1 requires “the name and Internet address of an organization other than the publisher that is intended to permanently archive the work in a manner that preserves the content and layout, and is capable of doing so”: we found no such repository mentioned on the journal website. This means that if the publisher closes its website, all papers will be lost. Article 8.5.3.2 requires “an ISSN for the journal containing the work”: the journal does mention an ISSN (2008–8019) but we could not retrieve this ISSN number from online systems such as WorldCat , to which Parasite adheres, advises special treatment in these cases. In this case, the peer review process was handled by an Invited Editor, Dominique Vuitton.The Editor-in-Chief of Parasite is one of the authors of this manuscript. COPE (Committee on Publication Ethics,


In recent decades, the pervasiveness of increased arterial stiffness in patients with cardiovascular disease has become increasingly apparent. Though, this phenomenon has been well documented in humans and animal models of disease for well over a century, there has been surprisingly limited development in a deeper mechanistic understanding of arterial stiffness. Much of the historical literature has focused on changes in extracellular matrix proteins—collagen and elastin. However, extracellular matrix changes alone appear insufficient to consistently account for observed changes in vascular stiffness, which we observed in our studies of aortic stiffness in aging monkeys. This led us to examine novel mechanisms operating at the level of the vascular smooth muscle cell (VSMC)—that include increased cell stiffness and adhesion to extracellular matrix—which that may be interrelated with other mechanisms contributing to arterial stiffness. We introduce these observations as a new concept—the Smooth Muscle Cell Stiffness Syndrome (SMCSS)—within the field of arterial stiffness and posit that stiffening of vascular cells impairs vascular function and may contribute stiffening to the vasculature with aging and cardiovascular disease. Importantly, this review article revisits the structural basis of arterial stiffness in light of these novel findings. Such classification of SMCSS and its contextualization into our current understanding of vascular mechanics may be useful in the development of strategic therapeutics to directly target arterial stiffness. Increased arterial stiffness is a significant consequence of the natural aging process, but it is also associated with the presence of underlying cardiovascular disease. As such, an increase in aortic stiffness is frequently observed in populations with hypertension, obesity and diabetes. Additionally, gender also plays a role in the manifestation of increased arterial stiffness, as women may be more vulnerable to its deleterious effects. Altogether, it is increasingly apparent that there is significant clinical value in assessing and fully understanding the phenomenon of increased vascular stiffness. A deeper understanding of the underlying mechanisms may help motivate future development of effective strategies to combat increased vascular stiffness by targeting novel cellular mechanisms and minimize associated cardiovascular disease risks.While the topic of vascular stiffness has been previously reviewed, in this analysis, we focus on describing how cellular mechanics may contribute to the structural basis of increased arterial stiffness. In this review, we consider individual components of the vascular wall, and briefly present a literature survey to discuss current concepts of how these may contribute to vascular stiffness. We also emphasize in this review new reports of a stiff cellular phenotype that appears to impact endothelial cells (EC) and, as we have recently observed, vascular smooth muscle cells (VSMC). For VSMC, our work has demonstrated that there is a significant increase in the VSMC stiffness and adhesion to the extracellular matrix (ECM) - that occurs in conjunction with increased vascular stiffness. We hypothesize that this cellular level stiffening alters vascular function and contributes to the changes observed in vascular stiffening observed in aging and cardiovascular disease, which we term the “Smooth Muscle Cell Stiffness Syndrome.” Although, syndrome is technically defined as a group of symptoms that consistently occur together, we are using this term to describe the concurrence of vascular smooth muscle stiffness within the broader field of vascular stiffness. We believe that understanding the mechanisms that underlie this Syndrome will provide new clues to help improve our understanding and therapeutic targeting of increased vascular wall stiffness.Changes in the mechanical properties of the vasculature are co-morbid with cardiovascular disease. Clinical studies have directly linked increased arterial stiffness to several risk factors for cardiovascular diseases—including hypertension  and after aging (over 20 years old). We found that aortic stiffness increased, but much more in old males than females Figure , consistThe most common mechanism thought to mediate increased vascular stiffness involves remodeling and content changes in the ECM of the aorta, with increases in collagen and decreases in elastin. Many studies can be found dealing with the structural content and properties of ECM proteins, predominantly collagen, elastin and fibronectin. Elastin is highly abundant in large and small arteries and in the aorta confers distensibility to account for the recoil ability of the aorta. At low mechanical loads, vascular mechanical properties are predominantly determined by elastin fibers. At these loads, collagen fibers have been histologically shown to have a loose, wavy configuration suggesting that they are not load-bearing. Upon higher mechanical loads, mechanical force transfers to the collagen fibers and they can be observed to straighten and lose their wavy appearance suggestive of bearing greater loads and thus contributing to a larger degree to the mechanical properties of the vessel. These relative mechanical contributions of elastin and collagen are thought responsible for the characteristic stress-strain curve of the arterial wall. Increased arterial stiffness has thus been proposed to be associated with increases in collagen content that occur concomitantly with decreases in elastin content. Numerous studies of aging vessels have reported increases in the collagen/elastin content ratio, and have associated this conclusion with the increase in arterial stiffness with aging. In fact, this view of increased collagen and decreased elastin has dominated thinking in the field of arterial stiffness to the point that it has become conceptually dogmatic.However, an in depth analysis of published studies of hypertension strongly suggest that this view of an increased collagen to elastin ratio may not be entirely accurate. Several reports have demonstrated a lack of increased collagen in hypertension  have been reported to be directly involved in mechanotranduction , endothelial derived hyperpolarizing factor and prostacyclin (Bellien et al., One interesting hypothesis has been advanced by Oberleithner and colleagues has been that aberrant endothelial signaling may be the result of a mechanical stiffening of EC (Oberleithner, Recently, the contributions of inflammatory mechanisms to arterial stiffness have attracted interest. Several clinical studies have established a link between increased arterial stiffness independent of other cardiovascular disease risk factors in patients with various inflammatory diseases, such as rheumatoid arthritis (Klocke et al., As reviewed above, an increase in vascular stiffness can be observed in hypertension in in the absence of increased collagen content and decreased elastin content as the literature on this point is not consistent. This indicates that there are other operative mechanisms that require elucidation in the case of increased vascular stiffness. Furthermore, it also suggests the need to re-examine the temporal, structural and mechanical basis of arterial stiffness at smaller lengths of scales.It is intriguing to speculate that perhaps structural explanations beyond changes in the ECM protein content and type for arterial stiffness have not been forthcoming for technical reasons. However, it is quite clear from the literature that the mechanical properties of the ECM must be considered. An appreciation for the pathophysiology of altered mechanical properties of arteries was first noted by Roy in the nineteenth century Roy, . After tBy extension, this structural mechanism has been applied to explain the increased arterial stiffness present in hypertension and this notion has persisted despite numerous controversial reports that do not necessarily support the proposed directionality of changes in collagen and elastin content in hypertension. Cox was one of the first to suggest that intrinsic differences in the mechanical properties of smooth muscle may be responsible for arterial stiffness. He based this conclusion on the finding of no innate difference in collagen and elastin coupled with the presence of increased stress development by vasoactive stimulation in hypertensive smooth muscle even after normalized to the smooth muscle content area Cox, . DespiteThe introduction of “Stiff Cell Syndrome” with respect to EC Lang,  and our In conclusion we would suggest the presence of alternative mechanisms, rather than only changes in the ECM, as contributors to increased arterial stiffness. We introduce the concept of smooth muscle cell stiffness syndrome, to incorporate new information that increases in vascular stiffness are accompanied by increases in the stiffness and adhesiveness of VSMC at the cellular level. Importantly, modulation of these cellular mechanisms may be an opportunistic target toward the development of novel pharmacological therapeutics for hypertension and arterial stiffness.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.


Kidney transplantation is the therapy of choice for end-stage kidney disease. Graft’s life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term.RT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction.The CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship . Living donors showed higher mean CCBF levels than brain-death donors at each point in the study. These significant differences persisted at month 12  despite similar serum creatinine levels (1.5 ± 0.3 and 1.5 ± 0.5 mg/dL). A sole rejection episode was associated with lower overall CCBF values over the first year. CCBF defined better than level of serum creatinine the graft function status at medium-term.RT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation. We have described the natural history of cortical capillary blood flow under regular clinical conditions. Kidney transplantation is the therapy of choice for end-stage kidney disease when the patient and graft conditions are optimal. Despite significant therapeutic and immunological advances, the graft’s lifespan is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression –3. SerumRenal cortical microcirculation is recognized as an important part and target in the response of a grafted kidney and especially affects chronic damage . In otheOur hypothesis is that numerous graft lesions start by affecting the vascular network ,10,11 can be measured by real-time contrast-enhanced sonography (RT-CES), a technique that has recently been made available. This technique provides an analysis of vascular refilling in any region of interest . A perfusion study can be performed by continuously injecting microbubbles, which are then destroyed by an ultrasound pulse with a high mechanical index. Vascular refilling can also be quantified by performing time-intensity curves using a software tool. The refilling of an area is therefore a marker of tissue perfusion ,13. Its The primary aim of our study was to describe the natural history of cortical capillary blood flow to explore the various patterns of this parameter over time under diverse conditions of kidney transplantation. A secondary study objective was to explore the influence of donor conditions and recipient events  on CCBF. The third objective was to determine the capacity of CCBF for improving the predictive value of current plasma creatinine levels in the medium term.We evaluated all patients who underwent kidney transplantation in our unit from 2009 to 2010 by RT-CES, with no other inclusion/exclusion criteria. The study was approved by our institution’s ethics committee . Patient records/information was anonymized and de-identified prior to analysis.Immunosuppression is a key study variable, considering its ability to induce changes in the renal vascular network by calcineurin inhibitors ,21We theThe maintenance immunosuppression therapy also included steroids and MMF, adjusted according to the patient and graft outcomes.The study variables were obtained from our renal transplant data base and included the following:Donor: origin , donor cause of death , age, sex and history of hypertension and diabetes.Recipient: age, sex, type of and time on dialysis, kidney disease diagnosis, other previous kidney grafts, warm and cold ischemia times, immunosuppressive drugs (see prior section), delayed graft function , acute rejection episodes(demonstrated by graft biopsy), serum creatinine follow-up, glomerular filtration rate, proteinuria and trough serum tacrolimus levels coinciding with the sonography, number of HLA-A, B and DR loci mismatches and percentage of panel reactive antibodies.RT-CES consists of B-mode sonography with Doppler and contrast administration. Sonography was performed with an Acuson Sequoia ultrasound system and a 4C1 convex transducer , at a frequency of 1.5 MHz in transmission and reception. Initial kidney visualization was performed in a sagittal imaging plane at 3.5 MHz with a mechanical index (MI) of 1.Initially, conventional graft B-mode sonography and Doppler scan were performed. Measurements of the graft  were performed. The resistance index was obtained from the area of the proximal segmental arteries .2. Scanner calibration was performed according to manufacturer specifications following the International Electrotechnical Commission’s recommendations. The gain settings, depth and focus were optimized and maintained constant throughout each study.Contrast-enhanced sonography was then performed with Cadence contrast pulse sequencing (CPS) at a low MI (0.2–0.5). Microbubble destruction was performed in the Cadence CPS imaging mode by applying an MI of 1.9 with a continuous frame rate of 14 Hz. Information about the Cadence output running in the CPS imaging mode at an MI of 1.9 is as follows: peak rarefactional pressure, 2.1 MPa; distance from the transducer output face to the point of maximum pulse pressure squared integral, 87 to 38 mm; and spatial-peak temporal-average intensity, 607 mW/cm®; Bracco SpA, Milan, Italy) through the peripheral vein in a continuous perfusion  with constant agitation. The initial infusion  was performed at 4 mL/min. Optimal kidney graft contrast visualization was usually achieved at 30–60 seconds.The transducer was held in a fixed position to scan the graft in a longitudinal cut. When major kidney structures were barely visible, a contrast agent was applied. Each patient was administered a contrast agent , which provided time-intensity curves using the software tool . The rep®; Siemens Medical Solutions). Three circular regions of interest (ROI) were selected in the subcapsular renal cortex, 2in the renal cortexmore proximal to the transducer and 1in the contralateral renal cortex  for a 95%confidence interval. So, in this actual study, interobserved reproducibility was not performed because methodology was similar to the 2007 study.post-hoc comparisons were considered using the Bonferroni correction.Data are shown as mean ± SD and medians and quartiles are employed when there is a non-normal distribution. Qualitative variables are expressed as percentages. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The Serum creatinine was selected as the prognosis marker for graft outcome following the recommendations of several authors –27. The During this period, 89 kidney transplantations were performed in our institution. Ten patients were excluded from the longitudinal study due to premature graft loss (during the first 15 days):two grafts from circulatory-death donors never functioned. Five grafts (one of then from circulatory-death donor) suffered graft thrombosis in 24 hours. One recipient suffered immediate hemorrhagic complication and required transplantectomy before 24 hours. A recipient died because of myocardial infarct at day ten with very good graft function. One recipient suffered delayed graft function and humoral acute rejection and never functioned (a transplantectomy was performed).As a result, 79 grafts  were finally studied since the aim of our study was to explore graft CCBF over time more than observe the immediate values. Patient characteristics are shown in We attempted to define the natural history of CCBF using the results of examinations performed during the first week and at months 1 to 12 after transplantation; these values are shown in The natural history of CCBF will depend on donor conditions and the subsequent influences on the recipient.We observed that grafts from living donors showed significantly higher mean CCBF levels than grafts from brain-death donors at each point in the study Figs  and 5. FIn contrast to brain-death donors, it is remarkable that circulatory-death donor grafts showed an initial CCBF(2–7 days) value similar to that of living donors and significantly higher than that of brain-death donors. Two of these grafts never functioned and were excluded from the analysis. The other 4 showed delayed graft function (DGF) and were followed by renal biopsy per protocol. CCBF values of these 4graftsshowsimilar values to that of living donors at day 7 and month 12. Median CCBF values were 44.5 at day 2, 45.6 at day7 and 49.8 dB/sec at month 12.Acute tubular necrosis, present in brain-death and circulatory-death donors, was not differentiated except for the different CCBF levels, representing an added value for the examination of these uncertain situations that usually require renal biopsy.We observed that brain-death donor age and CCBF levels showed an inverse significant relationship  . This reBrain-death donors younger than 40 years showed CCBF values that were no different from that of living donors at almost all study stages, in contrast to the lower values showed by donors over 59 years of age.Other donor conditions were also analyzed  although there was no significant relationship between any of these conditions and CCBF.Neither the type of dialysis nor the cold ischemia time showed any correlation to CCBF. The presence of DGF did not significantly affect the CCBF curve morphology over the first year, although these values were slightly higher at months 3 and 12 in the non-DGF group (mixed models).Immunosuppression induction: Given that the use of calcineurin inhibitors can affect CCBF levels, we compared CCBF values under early and delayed use (these recipients were treated with Thymoglobulin). Although it is our practice to prescribe thymoglobulin for higher risk patients with DGF, the data demonstrated a higher CCBF value over the first month relative to those taking tacrolimus since the first day . In contrast, patients who started tacrolimus at day 1 demonstrated a transient decrease in CCBF levels during the first week. This observation suggests the possibility of vessel constriction induced by tacrolimus. No differences in terms of CCBF were observed between these groups at month 12. We observed no correlation between CCBF levels and simultaneous tacrolimus trough plasma levels at any time.Eight cases had an acute rejection episode demonstrated by a renal biopsy. Coinciding with these episodes, CCBF showed non significant lower values relative to patients not experiencing graft rejection. Furthermore, the presence of a rejection episode was significantly associated with lower overall values over the first year , left. TTo compile the data obtained from donor/recipient conditions and their relationship to the CCBF value at various times, we performed a multivariate analysis. There was an independent significant relationship between CCBF and donor type (living vs. brain-death), donor age and serum creatinine level. The presence of acute rejection was almost significant, but the other variables did not remain in the model. rd year).CCBF levels measured at ROIs 2 and 3 in the proximal cortex and ROI 4 in the deep cortex were averaged to obtain the mean graft CCBF and correlate this value with that of plasma creatinine values and glomerular filtration rates (GFR) in the medium and long term , GFR measured by 24-hour urine creatinine clearance  and estimated GFR measured by MDRD  at month 3 (p<0.05). However, there was no correlation with these parameters measured later on during the follow-up.Plasma creatinine levels at month 1 were significantly correlated with plasma creatinine levels and GFR at all measured points until year 3. However, when patients with CCBF in the highest tertile (>44 dB/sec) at month 1 were compared with those in the lowest tertile (<25 dB/sec), both groups had similar creatinine levels (1.8–1.9 mg/dL). The first group achieved higher renal function in all measurements from month 3 to year 3 .Plasma creatinine levels at year 1 were significantly correlated with plasma creatinine levels and GFR at all measured points until year 3. There was also a significant positive correlation between CCBF at year 1 and GFR at years 1 and 3. Once again, when patients with CCBF in the highest tertile (>38 dB/sec) were compared with those in the lowest tertile (<26 dB/sec) at year 1, there was no difference in mean plasma creatinine levels . The first group achieved a significant higher GFR at year 3  .CCBF had consistently better predictive ability than plasma creatinine. CCBF values correlate throughout the study period, whereas long-term plasma creatinine levels correlate well with month 1 plasma creatinine levels but not with intermediate levels.This study demonstrates that an innocuous examination such as RT-CES is able to accurately quantify and iteratively measure cortical graft microcirculation in kidney recipients. Others authors have communicated in elegant studies their experience with graft RT-CES, even with histological correlation in transversal studies , standinOur results suggest that CCBF has wide interpatient variability ,21,28andWe should recognize the significant interpatient variability ,21,28, w20. However, the later use of these drugs had similar results to those of patients who were not treated with these drugs. The vasoconstrictor effect appears to be transitory, and a negative effect from tacrolimus should be considered in the recovery phase of tubular necrosis and delayed graft function.The absence of anticalcineurin drugs was associated with a higher initial CCBFAcute rejection is associated with lower CCBF in general, as a result of tissue edema and infiltration. However, CCBF did not demonstrate sufficient sensitivity to distinguish rejection , althougthere was no correlation between the estimated GFR and the RI at 3 or 24 months. At 12 months there was a weak correlation ”. When they tried to associate RI with histologic findings, in protocol biopsies, “there was no significant or consistent correlation”. Beside, RI was associated with patient survival but not with graft survival. We have not found correlation between resistive index and CCBF at any time (data not shown), possibly because CCBF reflects both donor and graft characteristics as it can be deduced by the CCBF correlation with donor´s age, acute rejection episodes, and living vs. brain-death donor and not with recipient individuality. We speculate that CCBF could reflect first the basal vasculature state from the donor and that afterwards this state changes by several inflammatory insults after ingraft.Naesens M. et Al  establisThe medium-term (3 years) prediction of graft function is of interest because it determines the whole graft project. Nonextreme serum creatinine levels at various points during the graft function follow-up have limited prognostic value. However, we have been able to demonstrate CCBF’s greater predictive value at month 1 and year 1 and for GFR at year 3 relative to serum creatinine levels, specifically for plasma creatinine values lower than 2 mg/dL. Serum creatinine levels are determined by GFR at any time. Its ability to predict overall graft outcome is intrinsically limited by the circumstances that condition GFR. However, it is recognized that the level achieved by the first year has a certain predictive capacity for medium-term graft outcome. Previous creatinine levels do not have this ability, except when GFR is low or zero, in which case the creatinine levels remain high, signaling a lack of renal function.In contrast, both isolated and grouped CCBF values over the first year showed a peculiar behavior with predictive capacity. It remains to be seen whether these results can be extended to the future, allowing us to predict long-term renal function using CCBF, thereby converting it into an innocuous marker of great importance.Since this is a pilot study, RT-CES cannot surpass conventional methods for assessing graft function such as serum creatinine measurement or proteinuria. By the present RT-CES is a useful, inoffensive and iterative tool to explore graft wellness and induce suspicion that indicates other invasive diagnostic methods.Our study had a limited number of patients at a single center. Due to the significant interpatient variability, a larger study population would be desirable. The study was performed under standard clinical practice, although it was not controlled or randomized. So, we recognize in RT-CES is a tool that can accurately quantify and iteratively measure cortical graft microcirculation in kidney recipients. We have described the natural history of cortical capillary blood flow under regular clinical conditions and shown how it could become a reference for clinicians who use contrast-enhanced sonography in this field. The novelty of this study lies in its longitudinal nature in contrast with other cross-sectional studies published until now. The CCBF data are consistent with the clinical variables evaluatedand therefore in line with current knowledge. More studies with a homogeneous design are warranted to confirm these results.S1 VideoEach videoclip has been performed at a different time from the ingraft . The patient received a kidney from a 40-year-old male brain-death donor. The recipient was a 33-year-old man, and this was his second graft. He did not experience delayed graft function or acute rejection.(MP4)Click here for additional data file.


Joint stiffness is a common, debilitating, age-related symptom, which may be seen after total joint replacement (TJR). Stiffness also occurs in fibrotic conditions such as shoulder capsulitis and Dupuytren's contracture. We speculated that the two traits (TJR and fibrotic disease) are linked pathogenically.Using the TwinsUK NIHR BRC BioResource we tested the hypotheses that 1) joint (hip and knee) stiffness, TJR (hip and knee), and fibrotic conditions are associated and 2) genetic factors contribute to them.Participating twins (n = 9718) had completed self-reported questionnaires on the traits of interest. All three traits were significantly associated with increasing age and body mass index (BMI), as well as female sex, on univariate analysis. Multivariable logistic regression analyses showed a significant association between TJR and joint stiffness  and between fibrotic conditions and joint stiffness , adjusting for age, sex, BMI and twin relatedness. Monozygotic versus dizygotic intraclass correlations gave heritability estimates for TJR = 46% and joint stiffness = 32%.That fibrotic conditions, joint stiffness and TJR are significantly associated suggests a common disease process, possibly fibrosis, which is genetically mediated. Joint stiffness is a common, debilitating symptom that significantly affects quality of life. Total joint replacement (TJR) is the treatment of choice for end stage, painful, stiff joints, usually the result of osteoarthritis. More than 90,000 total knee replacements are performed each year in the UK . A numbeTwinsUK is the UK's largest registry of monozygotic (MZ) and dizygotic (DZ) twins. It contains extensive genotype and phenotype data obtained at clinical visits and by mailed and online questionnaires. The twin characteristics have been shown to be similar to the general singleton population for a range of traits and lifestyle factors . TwinsUKParticipants were selected from the TwinsUK registry  on the aLogistic regression analysis was used to determine the association between the three traits of interest, joint stiffness, TJR, and fibrotic conditions, adjusting for age, sex, BMI and the twin relationship. Heritability estimates were calculated by comparing intraclass correlations in MZ versus DZ twins for TJR and joint stiffness (frozen shoulder was reported previously). For the purposes of this analysis, missing data were assumed to be negative, thus biasing the study towards the null. Statistical analysis was performed using Stata software .The sample comprised 9718 twins having information on at least one trait at any time-point . Of those twins reporting joint stiffness and/or a fibrotic condition , 95 had undergone a TJR, compared with 283 out of 8729 without fibrosis or joint stiffness . Univariable logistic regressions were also used to model the magnitude and significance of the associations (Increasing age and BMI were found to be significant risk factors for both joint stiffness and TJR. Twins reporting a fibrotic condition were more likely to complain of hip or knee joint stiffness (60/762 (7.9%) versus 227/8956 (2.5%), p = <0.001, Pearson χciations  and showResults of regression analyses considering all traits together are also shown in Comparison of the intraclass correlations in MZ versus DZ twins for TJR and joint stiffness is shown in The symptom of joint stiffness is linked with various pathologies and is not predictable. We have explored the relationship between stiffness, fibrotic conditions and the propensity to large joint replacement, based on the notion that genetic influence may modulate the susceptibility to fibrosis. We have shown, for the first time, an association between fibrotic conditions , joint stiffness and TJR, which is evident in this large dataset, even after adjusting for known risk factors, such as age and BMI . FurtherA number of different factors contribute to the decision to replace a joint, including total loss of joint space on plain radiograph, as a marker of endstage osteoarthritis. Knee osteoarthritis itself also has a significant genetic component, with heritability estimates of ~40% . A sibliThis was an initial, observational study and there are several limitations. Connective tissue research is limited by accurate disease definition. Diagnosis of arthrofibrosis and frozen shoulder remains difficult and the self-reported data included pain, as well as stiffness. However, the incidence of fibrotic conditions here is similar to that reported previously , 6 and tTreatment options for fibrotic joint conditions are severely limited at present, and include stretching or surgically removing the fibrotic tissue; they do not address the biological basis of disease. This limited physical approach to the tissue may contribute to a recurrence of fibrosis, which is frequently seen . A betteS1 AppendixThe entire dataset used in this study is presented in the file S1 Appendix.(XLSX)Click here for additional data file.


Multicenter databases are useful tools for quality improvement programs. Most of this evidence is based on studies in North America and Europe and little is known in other regions. Since 2011, a Brazilian private cardiovascular center has joined an international registry of cardiac surgeries.To evaluate changes in quality indicators and clinical outcomes of cardiac surgery patients after a multifaceted educational program based on reports of an international database.A multifaceted and continuous educational program based on trimestral reports from the international database was implemented in a Brazilian cardiovascular center. A local team targeted reductions in the time of mechanical ventilation (MV), in length of stay and in the number of inappropriate transfusions. A pilot protocol for rational use of blood products based on guidelines was developed in 2011 [From January 2012 to December 2013, 667 CABGs were performed. The predicted risk of in-hospital mortality by the score of the Society of Thoracic Surgeons (validated in the hospital [These results indicate that quality improvement program based on international database reports can improve outcomes in a Brazilian private hospital. Global registries can be useful tools to overcome gaps in clinical practice in different countries.


Purpose. Although the use of buccal mucosa in substitution urethroplasty has been practiced for some years, it has not been free of controversy over which surgical technique is the most appropriate to use. There is paucity of data in Sub-Saharan Africa about its success; this study presents the outcomes of dorsal and ventral buccal graft urethroplasty at a sub-Saharan tertiary hospital. Methods. This is a prospective study in which buccal mucosa was used for ventral and dorsal grafts; followup was up to two years. All patients provided informed written consent for the procedures. Results. Seventy-two patients with bulbar urethral strictures underwent buccal graft one-stage urethroplasty. Mean age was 55 years; etiology of the strictures was postinflammatory due to urethritis from sexually transmitted infections 97% (70/72) and trauma 3% (2/72). Buccal mucosa grafts were harvested from the cheek using a two-team approach. Grafts were placed on the ventral and dorsal urethral surfaces in 32 and 40 cases, respectively; the success rate was 84 and 80%, respectively. Repeated urethroplasty was successfully done among 10% (7/72) and patients reported resolution of symptoms in the follow-up period. Conclusion. There was no difference between dorsal and ventral onlay buccal graft outcomes for bulbar urethral strictures. The success rate was 80 to 84%. Urethral stricture is a chronic and common urological problem and difficult to manage fraught with high patient morbidity and stricture recurrence , 2.Since the resurgence in the use of buccal mucosa grafts (BMG) in substitution urethroplasty in the late 1980s, there has been controversy over which surgical technique is the most appropriate for its application. In experienced hands the results of the ventral and dorsal onlay of BMG for bulbar urethroplasty are the same .BMG has become an ideal urethral substitute because of ease of harvest, surgical handling characteristics, hairlessness, and compatibility in a wet environment and it is early in growth and graft survival; because of these unique characteristics, buccal mucosa has gained popularity in the realm of reconstructive urology.Standard bulbar urethroplasties using BMG should have a lifetime success rate approaching 92% , 4.There is paucity of data on this subject in Sub-Saharan Africa; the purpose of this study was to compare ventral and dorsal onlays for bulbar urethroplasty in a low resource setting.This was a prospective study.It is performed at a tertiary referral hospital at Mulago over a two-year duration (2010–2012).Consecutive patients presenting with difficulty in passing urine  due to a penile urethra stricture were recruited in two phases: over a 12-month period for dorsal onlay grafting and the subsequent 12 months another set was recruited for ventral onlay grafting.Those with concomitant symptomatic prostate enlargement were excluded.All patients provided informed written consent for the procedures.We collected data using a questionnaire; data were extracted from the patients files and entered in an excel spread sheet and then exported to SPSS version 17 and analysis was done using descriptive statistics.A urethral stricture was diagnosed through history taking and physical examination and confirmed on performing a cystourethrogram (ascending and micturating urethrogram). Recurrence (failure) was defined as a need for additional surgical procedure or filiform bougienage within the follow-up period. The followup was up to 2 years.Variables studies included level of client satisfaction; patients were asked if they were satisfied or not with the ease of voiding urine, erectile dysfunction (ED), and postvoid dribbing. ED was considered if it was of sudden onset and did not exist prior to surgery. The question asked was if at any time after surgery erections were insufficient for intercourse in comparison to before surgery . PostvoiThe success of urethroplasty was from the patient self-reports of improved urine stream, complete emptying, and reduced frequency.We used a two-team approach for graft harvest and perineal dissection. The perineal dissection team laid the stricture open to determine its length before the graft harvest team proceeded.The buccal harvest technique below was described before in 2011 [Patients were instructed to use a mouthwash containing chlorhexidine in the preoperative period. All the patients received intraoperative antibiotics (Ceftriaxone and Metronidazole) intravenously before the oral mucosa was excised. The face and cheek were prepped with 0.5% chlorhexidine and draped in the usual sterile manner with sterile linen. Three 3/0 silk sutures are placed through the lip to provide traction. A mouth gag and a retractor were used to facilitate exposure. Using a marking pen, the graft was outlined 2.5 cm wide and as long as required.0.5% of bupivacaine with epinephrine were injected underneath the graft for preemptive analgesia and intraoperative haemostasis. The graft was incised and dissected off of the buccinators muscle, while avoiding Stensen's duct. The graft was pinned out and thinned on the back table. It was kept in saline until the time of transfer. The donor site was left unstitched as a routine practice –8.Donor site is packed with a gauze piece soaked in adrenaline and lignocaine. The oral pack is removed in the evening and the patient is asked to rinse his mouth with cold water and dilute mouthwash. The cavity was inspected for any bleeding and the patient asked to start cold oral liquids in the evening. In a day or two the patient was advised to shift to semisolid, nonspicy diet and can consume normal diet as soon as he can tolerate it.Patient was placed a high lithotomy position, properly padded and secured. Subsequently the patient's perineum was prepped with 0.5% of chlorhexidine and draped in normal sterile fashion.A 22F catheter was used to delineate the urethral contour and to determine the exact location of the distal portion of structure; a number 15 blade scalpel was used to incise the urethra over the urethral catheter and the urethral stricture is opened completely. The lumen of the structure was intubated with either an 8F-feeding tube or with a small (<8 mm) guide wire, and the stricture was incised until normal urethra was identified. Both proximal and distal urethral stumps were bougied to ensure they are wide open to 30F.The buccal mucosa was then sewn onto the ventral defect using a running and interlocking 5/0 vicryl suture, for a good seal. An F16 silicone catheter was placed through the urethra. The tunic of the spongiosum is closed over the graft for a well vascularized bed. The bulbospongiosus muscle was closed with a running 3/0 vicryl and the skin was closed with multiple vertical mattress stitches using 2/0 vicryl rapide. Prior to skin closure, the wound is anaesthetized with 0.5% bupivacaine.The technique employed was similar to the one outlined by Barbagli et al, 2006 .For the follow-up period, the catheters were removed on the 21st day after the operation was done. No uroflowmetry was done. It was not available to clients. And no pericatheteric urethrograms were done.The mean age was 55 years, the age range was 10–86 years, and the recurrence rates were 16–20%.40 dorsal grafts provided success in 32 (8 failed cases) and 32 ventral grafts provided success in 27 (5 failed cases).70 were postinflammatory (infection). 2 were trauma related.We found that dorsal and ventral onlay grafts offer the same performance; the recurrence rates were 16–20%, comparable with data from elsewhere –13. The The etiology of these strictures was postinflammatory (infection) for the most part (97%) as is common in low resource settings where urethritis due to sexually transmitted diseases is prevalent .For the most part, the outcome for both dorsal onlay grafts and ventral onlay grafts in bulbar urethroplasty is similar. The findings in this study affirm that the ventral onlay technique is, however, less cumbersome and therefore more suitable for surgeons new to the practice of urethroplasty. The complications associated with ventral onlay techniques can be minimized by meticulous surgical technique, but in series with longer followup, complications still tend to be more prevalent. In urethroplasty, two-stage dorsal onlay of BMG (after complete excision of the scarred urethra) still provides the best results, although in certain circumstances a one-stage dorsal onlay procedure is possible . In geneThe most common graft materials in use today are buccal mucosa (BM), preputial skin (when available), and penile and preputial skin flaps with their own blood supply. The most appropriate use of these materials has long been the subject of controversy, especially in terms of which type of tissue and whether as a graft or flap and at which site along the urethra –13.The use of BM in urethral surgery was first described in 1941  but not When substitution procedures are necessary, historically various tissues have been used including genital  skin, extragenital skin, bladder mucosa, and buccal mucosa. These tissues have been used as either pedicled flaps with their own blood supply or as free tissue grafts. The use of colonic mucosa has also been reported, but this is not validated yet and seems to involve a significantly greater degree of morbidity for graft harvest than any of the other methods mentioned.There was no difference between dorsal and ventral onlay buccal graft outcomes for bulbar urethral strictures. The success rate was 80 to 84% after an average follow up period of one year.This was a single-site study and by one operator experienced in dealing with urethral strictures. CUG (cystourethrogram) was only done for those experiencing difficulties in passing urine; no follow-up cystoscopies were done (for any patient). Poor oral hygiene and the use of tobacco were not factored in as potential confounders; these factors are known to influence the outcome of the BMG . The mea


Biochim. Biophys. Acta. 2012 Aug; 1820 (8):1205–1213. doi: 10.1016/j.bbagen.2011.10.003. Epub 2011 Oct 13. Review. PMID: 22020049]. The authors regret not having detected their error and apologise to the readers of the Journal for any confusion this may have caused.The authors and the journal retract the 9 February 2012 article cited above. This article is a duplicate of an article that had been previously submitted for publication in another journal [Molecular structure and target recognition of neuronal calcium sensor proteins, Ames, J. B., Lim, S.,


Transparently documenting who and why a person is an author of a clinical trial report, as with any other article, is important since it allows research team members appropriate recognition and also likely helps reduce or avoid problems such as ghost authorship. Marušić and colleagues have previously proposed a five-step framework for attributing authorship of pharmaceutical company-sponsored clinical trials. The process is short, easily implemented, and can be used in addition to the authorship guidance provided by the International Committee of Medical Journal Editors. For the framework to gain optimal traction it is important that a strong implementation plan is developed and carried out across a broad spectrum of stakeholders. Authorship brings with it important responsibilities; authors must ensure that articles baring their names must be fit for purpose. This will help guarantee an increased value for published reports of clinical trials.http://www.biomedcentral.com/1741-7015/12/197Please see related article:  Complexity is the enemy of transparency” [BMC Medicine publishes another paper on journalology (publication science) [“parency” . Today, science) . Attribuscience) . The resWhat is positive about this research is that the proposed attribution process for authorship is brief, and not complex; it’s only five-steps. It is meant to augment the guidance provided by the International Committee of Medical Journal Editors . To enhaIf this authorship initiative is to be successful it requires endorsement and, more importantly, implementation. As Marušić and colleagues note , previouTrials – regularly publishes them. Additionally, with the requirement of trial registration, this framework could also be used when completing the investigator information part of the registration.Marušić et al. are silent on whether their framework can be used when developing authorship for submitting clinical trial protocols for publication consideration . Making Most of us are not born authors. It is an acquired skill that often starts during graduate school. This is where all journalology issues, including those pertaining to authorship issues  should be formally taught and discussed. Developing such skills early can translate into something useful throughout a researcher’s (author’s) career. It is unfortunate that almost all universities, and other centres of higher learning, appear to have abdicated their responsibilities regarding formally teaching journalology; the irony is not lost on me. These institutions are the very same places developing the next generation of biomedical researchers. Universities need to set aside appropriate resources to enable and promote such courses, and others, related to journalology .While authors have rights and privileges, they also have important responsibilities that require much greater attention. Given the opportunity of authorship, it is equally important to assert this responsibility. Authors must ensure that papers baring their name are “fit for purpose” . Here, aDisclosing authorship transparently is important for any manuscript being submitted to a biomedical journal for publication consideration. The responsibilities associated with authorship must be taken seriously. This might help increase value and reduce avoidable waste of biomedical research.


The Spring 2016 issue of the International Journal of Telerehabilitation (IJT) presents original and innovative work in three diverse sections: usability, intervention, and pedagogy, followed by a book review on teleaudiology. The contributors to this issue are notably multi-disciplinary and include an audiologist, computer scientists, engineers, an epidemiologist, occupational therapists, a rehabilitation counselor, a physician , and speechlanguage pathologists. The common thread linking the Journal’s authors and their manuscripts, is excellence in telerehabilitation related innovation. One of the hallmarks of the peer-reviewed International Journal of Telerehabilitation (IJT) is the wide variety in the topics of the work presented, all of which relate to innovations in telerehabilitation. The Journal’s flexible format accommodates a variety of submission types: research studies, clinical reports, book reviews, country reports, and pedagogical notes. And, our authors and expert reviewers hail from multiple disciplines. It is especially gratifying that our contributors span the academic life cycle -- a mix of seasoned authors and new contributors. We are honored to serve as stewards of their work, and present it to our readers.The Spring 2016 issue of the International Journal of Telerehabilitation (IJT) follows this tradition. Herein, we present original and innovative work in three diverse sections: usability, intervention, and pedagogy, followed by a book review on teleaudiology. The contributors to this issue are notably multi-disciplinary: an audiologist, computer scientists, engineers, an epidemiologist, occupational therapists, a rehabilitation counselor, physician/physical medicine and rehabilitation, and speech-language pathologists. A common thread linking all articles and authors, is excellence in telerehabilitation related innovation.We applaud our publisher who facilitates the publication of IJT as an open source journal, with neither subscriptions, nor author fees. Our reviewers, editorial staff, and authors and their home institutions are similarly generous, so that current advances in the field of telerehabilitation can be widely disseminated.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 Fall, 2016. We cordially invite your submissions by September 2, 2016. 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


The affiliations of this manuscript were incorrectly listed. The correct affiliations are:1,2, Erel Levine2Benedikt Obermayer1 Systems Biology of Gene Regulatory Elements, Max-Delbrück Center for Molecular Medicine, Berlin, Germany2 Department of Physics and Center for Systems Biology, Harvard University, Cambridge, USAThe funding statement is incorrect and should read as follows:www.daad.de) and the MDC (www.mdc-berlin.de) (to BO), and the National Science Foundation (www.nsf.gov) through grant MCB-1121057. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.This work was supported by fellowships of the German Academic Exchange Service (


Acinetobacter spp. are ubiquitous gram negative and non-fermenting coccobacilli that have the ability to occupy several ecological niches including environment, animals and human. Among the different species, Acinetobacter baumannii has evolved as global pathogen causing wide range of infection. Since the implementation of molecular techniques, the habitat and the role of non-baumannii Acinetobacter in human infection have been elucidated. In addition, several new species have been described. In the present review, we summarize the recent data about the natural reservoir of non-baumannii Acinetobacter including the novel species that have been described for the first time from environmental sources and reported during the last years. Acinetobacter species. Among these techniques, 16S-rRNA, RNA polymerase subunit B (rpoB), and DNA gyrase subunit B (gyrB) gene sequencing, as well as DNA-DNA hybridization and whole genome sequencing provide good informative data for Acinetobacter taxonomic studies .Implementation of molecular techniques in research laboratories has greatly improved the identification of Acinetobacter species are ubiquitous in nature and can be found in different environmental sources such as hydrocarbon contaminated areas, activated sludge, sewage, dump sites, but also on vegetables, animals, and humans , mules, livestock , horses, lice and arthropods  , A. johnsonii (21%), A. radioresistens (12%), A. pittii (11%), and A. junii (5%). In contrast, A. baumannii and A. bereziniae were rarely detected and the authors did not find A. calcoaceticus or A. haemolyticus on the skin or the mucous membranes  of 192 healthy volunteers in the United Kingdom. As in the previous study, they found that the colonization rate was around 40% with A. lwoffii being the most frequently isolated species and the forearm being the most frequently colonized area. However, the distribution of the other species was different, Acinetobacter genomic species 15BJ (12%), A. radioresistens (8%) and only one individual carried the Acinetobacter baumannii- calcoaceticus complex  and the men volunteers were more colonized than the women  or by production inhibitory biosurfactants (Cray et al., Referring to these results, we showed here that the environment is the main reservoir of Acinetobacter. As a result, a large number of well characterized species were available and Acinetobacter remains an interesting model for taxonomist to study the natural diversity as well as the evolutionary history of this bacterium. In fact, recent studies suggested that climatic changes and pollution have the potential to alter the species distribution in the environment (Coelho et al., Acinetobacter species was the result of those ecological changes. On the other hand, there is an important question that remains unclearly answered: could these newly described Acinetobacter species have a potential role in human infection? In fact, several studies showed that uncommon and newly described Acinetobacter species such as A. septicus and A. bereziniae were involved in human infection and some of them were resistant to carbapenems (Kilic et al., A. schindleri, A. guillouiae, A. soli, A. ursingii and A. beijerinckii isolated from clinical samples (Dortet et al., Acinetobacter will be discovered soon in human infections thanks to more efficient molecular techniques used for bacterial identification.In this review, we showed also that the use of DNA based methods contribute to the progress in the field of the diversity of the genus Acinetobacter species are widely distributed in nature and that the contaminated environment may enhance the growth of these microorganisms. Further studies are nevertheless required to understand the behavior of Acinetobacter spp. and to elucidate the mode of transmission of those bacteria from these different habitats to humans.In conclusion, even if the present data derived from only few studies, it seems that almost all of the AA, MJ, MH, and MK contributed to the conception and design of the work, and to the acquisition and interpretation of the data. All authors contributed to the drafting of the manuscript and approved the final version to be published.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.


The durability of Long Lasting Insecticidal Nets (LLINs) in field conditions is of great importance for malaria prevention and control efforts; however, the physical integrity of the net fabric is not well understood making it challenging to determine overall effectiveness of nets as they age. The 2011 World Health Organization Pesticide Evaluation Scheme (WHOPES) guidelines provide a simple, standardized method using a proportional hole index (PHI) for assessing net damage with the intent to provide national malaria control programs with guidelines to assess the useful life of LLINS and estimate the rate of replacement.We evaluated the utility of the PHI measure using 409 LLINs collected over three years in Nampula Province, Mozambique following a mass distribution campaign in 2008. For each LLIN the diameter and distance from the bottom of the net were recorded for every hole. Holes were classified into four size categories and a PHI was calculated following WHOPES guidelines. We investigate how the size, shape, and location of holes influence the PHI. The areas of the WHOPES defined categories were compared to circular and elliptical areas based on approximate shape and actual measured axes of each hole and the PHI was compared to cumulative damaged surface area of the LLIN.The damaged area of small, medium, large, and extra-large holes was overestimated using the WHOPES categories compared to elliptical areas using the actual measured axes. Similar results were found when comparing to circular areas except for extra-large holes which were underestimated. . Approximating holes as circular overestimated hole surface area by 1.5 to 2 times or more. There was a significant difference in the mean number of holes < 0.5 cm by brand and there were more holes of all sizes on the bottom of nets than the top. For a range of hypothetical PHI thresholds used to designate a “failed LLIN”, roughly 75 to 80% of failed LLINs were detected by considering large and extra-large holes alone, but sensitivity varied by brand.Future studies may refine the PHI to better approximate overall damaged surface area. Furthermore, research is needed to identify whether or not appropriate PHI thresholds can be used to deem a net no longer protective. Once a cutoff is selected, simpler methods of determining the effective lifespan of LLINs can help guide replacement strategies for malaria control programs. Recent escalation of national bed net distributions and universal coverage campaigns stimulated concern and investigation into the integrity and durability of long lasting insecticidal nets (LLINs) under ordinary use conditions. Mass distribution campaigns are recommended to deliver LLINs to households, rapidly increasing population coverage and improving equity of bed net ownership . AttritiIn 2005, the World Health Organization Pesticide Evaluation Scheme (WHOPES) developed “Guidelines for laboratory and field testing of LLINS”  4]. Mor. Mor4]. In 2011, WHOPES published a second document “Guidelines for monitoring the durability of LLINs under operational conditions” . In addiThe integrity of different fabrics in laboratory settings have been compared using standard burst and tear strength tests identifying differences between weight, textures, and weave patterns . Techniqet al. reports that respondents perceived condition of the net may be more important than measuring the actual physical condition of the net [While challenges of accurately determining the counts, sizes, and locations of irregularly shaped holes on bed nets exist, there is an even greater need for a composite score or standard measure that quantifies the overall general physical condition of the net to address the question: “How do you determine when a net is no longer able to protect an individual sleeping under it from a malarious mosquito?” Until recently, there has been no consistent methodology for evaluating holes in nets that could serve as a standard by which net protectiveness could be measured. For example, is a net still protective with 2 small holes and one large hole, and how does that compare to a net with 4 medium sized holes? Prior to the development and routine use of the WHOPES recommendations, this question was addressed in many different ways with each study using unique approaches to measuring durability including different measurement tools, hole size categories, weights, algorithms, and thresholds. A few studies presented results of hole counts without a composite index of the physical durability –23; howe the net . These iProtection of an individual by a decaying net may decrease gradually, making it challenging to know exactly when a net is no longer functional and needs replacement. However, malaria control programs need to determine the optimal time to replace an entire population of nets. Many malaria control programs are replacing nets at three year intervals on the assumption that most nets will not be functional after that time. However, if the estimate of what is a “failed” net are too stringent, it means programs are replacing nets sooner than needed. If the estimate is too forgiving, then programs may be leaving people with nets that provide inadequate protection for an extended period of time. By incorporating information on the physical condition of LLINs in field situations and devising a method to better estimate a threshold of LLIN damage, programs may be better able to determine on average when a net fails and can design appropriate replacement strategies.The 2011 WHOPES guidelines provide a standardized protocol to assess physical condition of LLINS in field situations. Included in this guidance is a composite measure of the nets’ physical condition called the proportional hole index (PHI) which is intended to provide an estimate of relative net damage for comparison among nets. This measure categorizes holes into four sizes. The number of holes of each size are counted and recorded during field evaluations. The PHI is calculated by multiplying the number of holes in each category by the corresponding weight (based on the estimated midpoint area of each hole category) and summing this across categories. Several studies have already reported bed net durability in field conditions using this methodology , 45–49 .The PHI provides a much needed standardized approach to assessing the physical condition of a bed net in operational conditions. However, in order to develop a simple universal algorithm several generalizations are made on the size, shape, and location of holes. First, holes of all sizes are generalized into four categories based on an easy to measure finger/fist/head methodology. Holes > 25 cm in diameter are lumped together into one category, and holes < 0.5 cm are not counted. Second, the PHI assumes all holes to be circular when estimating the area of the holes. Third, the distribution of the holes of different sizes throughout the net is considered to be uniform. In other words, the PHI does not take into account the locations of the holes on the net. It is important to understand how these generalizations may influence the overall index and interpretation of the relative conditions of the nets. Moreover, the question remains, “at what PHI value is a net considered no longer protective?” Following the creation of the PHI, several studies have selected a cutoff  as wellDuring the measuring of holes in the laboratory, data were entered directly into handheld computers  using questionnaires developed with Visual CE software . Data were downloaded directly into a MicroSoft Access database . Data cleaning and analyses were performed using SAS version 9.32 . Analyses were performed using SAS survey procedures  to adjust for clustering and the study design. Log transformations were performed in order to obtain geometric means for variables that were not normally distributed. When appropriate, domain analyses were performed to obtain results separately for each year and LLIN type; and were stratified by district. Proc Genmod was used to test for associations between hole size and location. When determining the proportion of holes at different locations of the net, it was noted that the total surface area of the roof was larger than the total surface area of the distance bands around the sides. Therefore the proportion was weighted to adjust for the difference in surface area of the roof panel. The nonparametric Wilcoxon signed rank test was used to compare paired measures of hole areas for the same nets such as the area based on PHI categories compared to areas using a circle or ellipse. The Wilcoxon-Mann-Whitney test was used to compare mean hole areas between two groups, Kruskal-Wallis test for more than two groups, and Spearman correlation to test for associations between ordinal variables. No adjustments were made for multiple testing.The PHI is based on a weighted sum of the different sized holes grouped into four categories. The weights are calculated with the assumption that the holes are circular . This does not take into account the fact that many, if not most, holes on nets may be irregularly shaped. In the third year of the study, the major and minor axes of the holes were measured, and the ratio of the major to minor axes calculated. For perfectly circular holes, these values would be equal resulting in a ratio of one; however, for non-circular holes this ratio would be greater than one, and the larger the ratio, the more ‘narrow’ the hole .2 where the radius, r, was calculated as half the length of the major axis . The area of an ellipse was calculated as A = pi*a*b where a is ½ the length of the major axis and b is ½ the length of the minor axis  by summing the areas of holes using the WHOPES categories and 2) by summing the area calculated from the actual measured diameters of each hole. The PHI was calculated as described previously using thThe index weights in the WHOPES guidance are based on the estimated mid-point area of each hole category relative to the area of the mid-point of the smallest hole category. More specifically, the formula for the area of a circle is used to calculate the hole area based on the mid-point radius of a category. The areas for the medium, large, and extra-large categories are then divided by the small hole area to get relative weights see . For exaWritten consent was obtained by all study subjects or by their parent or guardian if they were under 16 years old. Participants signed or provided a thumbprint on two copies of the consent form, one of which was kept by the investigators and the other was given to the participants. Approval for this study and consent procedure was obtained from the Bioethical Committee of the Ministry of Health, Mozambique . CDC investigators participated under a non-research determination on the basis of routine public health evaluation.et al. [Results of the LLIN durability study using the WHOPES methodology can be found in Morgan et al. . To summIn general, there were many more small holes than large holes. The number of holes in each of the WHOPES hole categories overall were as follows: 57.2% of all holes were small, 34.7% medium, 5.7% large, and 2.5% were extra-large respectively in polyethylene nets and 70.6%, 25.4%, 3.0%, 0.9% were small, medium, large and extra-large holes in polyester . The dis2 for polyethylene and 166.3cm2 for polyester nets compared to 240.5 cm2 based on the WHOPES midpoint.The geometric mean and median areas calculated using actual axes measurements based on the area of a circle were in general smaller than the area using the assigned WHOPES midpoint for holes in the medium and large categories .Extra-large holes are classified as any hole with a diameter > 25 cm, and the WHOPES index uses a midpoint diameter of 30 cm to calculate the area. In this hole category, close to ¾ of the holes meet or exceed the midpoint (75.5% polyethylene and 76.0% polyester) and as a result their areas may be slightly to grossly underestimated using the WHOPES midpoint , Part A.Overall, the median and geometric mean of the composite interrupted surface area was larger using the WHOPES PHI categories than the actual estimated circular areas for polyester nets across all three years and for polyethylene nets in 2009; whereas the median and mean tended to be smaller for polyethylene nets in 2011 , row 1. The geometric mean estimate of holed surface area was roughly five times greater for polyethylene than polyester nets  and there was a difference in holed surface area by year for each brand .The laboratory hole counting procedure was modified in 2011 to include a tally of extra-small sized holes (< 0.5 cm in size) on all collected nets. Three nets, one polyester and two polyethylene, were not evaluated for extra-small holes. In total 16,096 holes of this size were tallied over the 130 nets evaluated . One netTo a certain extent, the number of extra-small holes in a net corresponded to the number of all other sized holes . The levIn the third year of the study, the major and minor axes of the holes were measured, and the ratio of the major to minor axes calculated. Small holes had a major axis about twice as long as the minor axis, and larger hole sizes were less circular (narrower) as can be seen by the increasing ratios with increasing size , Fig 1. The geometric mean and median areas for holes in the small, medium, and large categories calculated based on actual axes measurements using the formula for the area of a ellipse were smaller than areas calculated using either the area of a circle or WHOPES hole categories . The total hole areas were greater for polyethylene than polyester nets  . The rooIf a specific threshold value of hole surface area is selected as part of a set of criteria for replacement of nets such as the cut-offs proposed by the Vector Control Technical Expert Group, the corresponding number of holes of each size required to meet the threshold can be extrapolated. As an example, consider a cutoff of PHI larger than 299 for an unusable net , 45, 46,Depending on the chosen cutoff, many nets may be determined to be unusable just by evaluating the number of extra-large and large holes on the net. Using cutoffs of PHI = 1000, 750, 500, 300, and 100 with the 452 nets in this study, resulted in 27.7, 33.8, 41.9, 51.8, and 67.1 percent of nets deemed unusable, respectively. Of these, 74.0, 79.3, 80.6, 76.5, and 78.2 percent of the nets exceeded the cutoff just by counting the extra-large and large holes alone  may have unintended consequences. It is possible that a net with 4 large 24 cm holes  would be classified as still functional, whereas a different net with 5 large 10 cm holes  would be classified as needing replacement even though the total damaged area is more than four times larger in the former net. Since the actual size of the hole is not recorded, just the number of holes in each category, this inconsistency would be largely undetected.Moreover, an important question of interest “what cut-off(s) should be used to determine when a bed net or LLIN population has reached the ‘end of useful life’?” remains outstanding. The recent recommendations of the Vector Control Technical Expert Group at the Malaria Policy Advisory Committee Meeting proposed PHI cut-offs based on existing evidence to classify a LLIN into the following categories: 0–64 good, 65–642 damaged, and 643+ too torn . HoweverWhen the primary program goal has a more research focused objective to develop a system for evaluating existing bed nets to determine which model may most suitable in a particular area a more thorough investigation of the net condition may be necessary. This objective often requires a more rigorous research approach performed on a limited number of bed nets to understand the formation of holes; their size, shape, location, and cause of damage as well as estimate the total damaged areas of bed nets over their lifetime. In these cases improvements on the PHI may be warranted to get a more accurate picture of bed net damage, as well as to properly assess a new model, weave, or user setting and location and especially when new brands are introduced into the market.Results from this study show hole sizes were not symmetrically distributed within hole categories, but decreased in number as the size increased. As a result, the PHI overestimated the amount of holed surface area for small, medium and large holes. In contrast, extra-large holes were found to be underestimated compared to circular estimates. When considering the PHI composite measure, it was found to overestimate area for all years when compared to an elliptical based measurement. In addition it overestimated the area in polyester nets in all three years when compared to circular estimates using actual measured axes. However, the PHI underestimated the actual measured area in polyethylene nets for 2010 and 2011 compared to circular estimates, indicating that underweighting by using the midpoint from the extra-large hole categories has a greater impact (though fewer holes) than the overweighting from the small, medium, and large categories. This finding was more prominent in polyethylene than polyester nets as they tended to have more extra-large holes.Extra-small holes (less than ½ cm) are excluded in the WHOPES guidelines. They are likely too small for easy passage of mosquitos and therefore when considering efficacy of an LLIN, the net would still be considered an effective barrier for its user even with an extra-small hole. However, when explicitly considering the physical durability of LLINs in the context of lifespan and replacement, extra-small holes suggest overall wear on the LLIN, can unravel leading to larger holes, and may serve as an indicator of a reduced lifespan of the net compared to one without extra-small holes. Extra-small holes are often very challenging to observe and measure during field studies , as suchThe formula for the PHI assumes holes are circular; and in the field a hole is categorized based on whether one can insert a finger, fist, or head through the hole. These measures overlook the possibility of irregularly shaped holes. This study found that most holes were 2 to 10 times longer in one direction (more long and narrow than circular), and as result the area assuming the hole is circular tends to overestimate the actual holed area by roughly 2 to 10 times. It is possible that the formula of an ellipse better approximates the true holed area; however, this too does not account for irregularly shaped holes and is laborious to obtain.The largest proportion of holes was found to be located at the bottom 1/4 of the net. Certain sections of a net may be more prone to tears based on use or other factors; also certain areas of the net may be more likely for mosquitos to penetrate than others. By understanding what parts of nets are most vulnerable, measures can be taken to strengthen nets at these locations. Future studies may want to take into account not only the size of the hole, but also the location when calculating a composite index scores by weighting or adjusting the score based on the location of the hole (e.g. weight holes on the top of a net more than those on the bottom of the net if future studies show mosquitos are more likely to enter holes in the top of the net). Also note that the PHI ignores repairs in nets such as stitches, knots, patches.rd year also the perpendicular to the major axis (minor axis). It is possible that for irregularly shaped holes some measurement error was introduced. In addition, the shape of holes varied greatly, and approximating the holes as a circle or ellipse has potential for error. This study took place prospectively over the course of three years, during which 16.6% of the households did not retain all of the bed nets received during the campaign. A survivorship bias may have been introduced into this data if the condition of the nets lost due to attrition differed from that of nets measured in this evaluation. In addition, the extra-small hole analysis only took place on nets during the 3rd year of data collection, and results may not be representative for younger nets.There are some limitations of the current study that should be noted. This study was initiated prior to the initial release of the WHOPES guidance and as a result several of the logistical methods did not follow the finger/fist/head recommendations exactly. However, this analysis consisted of the more precise lab measurements, and should not be affected by this deviation in the design. Lab recorders were requested to measure the longest section of a hole (major axis), and for the 3This paper demonstrates that measuring the physical integrity of bed nets is multifactorial and requires a thorough understanding of the size, shape and location of holes. More research is needed to potentially refine the PHI measurement tool as well as improve the manufacture and development of more durable bed nets. Moreover, physical integrity is not the only determinant of overall protectiveness of a bed net and it is important to include insecticide activity and bioefficacy in an assessment. A few experimental hut studies have looked at the impact of insecticide on bed nets with and without holes , 7 10, , 10, 54 There is a programmatic need to develop a standard, reproducible, logistically simple, and comparable method to assess net condition under normal use environments. The PHI provides a standardized approach to estimate the total surface area (or relative area using the weights) damaged by holes on a net. Results of the current detailed analysis using bed nets collected over three years in Mozambique reveal some of the potential weaknesses of the PHI including: underestimating the contribution of really large holes, overestimating the contribution of smaller holes, ignoring extra small holes and hole location, and oversimplifying the hole shape as circular. More research is needed to better refine the PHI and to understand the factors associated with hole initiation and enlargement in field conditions. Information about the size, shape, location and type of holes may help develop a simple field strategy for assessing net usability in terms of physical integrity that will help programs develop plans for repair or replacement of nets. More importantly, further investigation is needed to determine what hole size(s) put net users at the greatest risk in order to determine the optimal time for net replacement.Bed net monitoring and evaluation (M&E) activities including coverage surveys and malaria indicator surveys are an integral part of national malaria control program activities and provide information on general bed net ownership and use. The PHI is designed to help determine whether a large population of bed nets are still protective or should be replaced; however, in field situations identifying and counting all of the holes in a net, tabulating the data, and calculating a PHI may be laborious and time consuming. Due to the large volume of nets under evaluation, a simpler method of determining the usability of a net based on its physical condition that could be easily incorporated in existing M&E activities would be of great value.Physical integrity assessments including both in depth analysis of a small sample of nets and simple field counting strategies on larger numbers of nets during household surveys can be used in conjunction with insecticidal activity monitoring to enhance malaria control efforts in the field and can help guide manufacturers to build longer-lasting bed nets.S1 TableColumns are as follows: NetID = unique Net ID, NetType = Brand of net, Year = year net was assessed, and total CNT = total numbers of damaged areas on net including holes, knots, stitches and seam tears.(TXT)Click here for additional data file.S2 TableColumns are as follows:: NetID = unique Net ID, DamageID = unique ID for point of net damage, Damagetype = type of net damage ), size = length of hole in cm, and location = distance for the midpoint of the hole to the bottom of the net in centimeters ).(TXT)Click here for additional data file.S3 TableColumns are as follows: NetID = unique Net ID, DamageID = unique ID for point of net damage,Top of net = indicator for whether the hole was on the roof of the net (1 = yes).(TXT)Click here for additional data file.


The Canadian International Medical Graduate Bottleneck: A New Problem for New Doctors.Re: The process of returning to Canada to complete our residency training varies by province, and there exists an irony in the process that is no more evident than in British Columbia (BC). Only 24 of 279 residency positions in BC were dedicated to international medical graduates (IMGs) in the 2012 match,The Dean of Medicine at the University of British Columbia (UBC), Dr. Gavin Stuart, stated in an interview, “clinical skills are probably one of the big areas of difference of Canadian graduates from those that are graduating from Ireland or Australia… those individuals may have comparable knowledge base, [but] have not had the clinical exposure.”Unless there are significant changes to better allow CSAs to return home upon graduation, more and more students will find themselves unable to serve Canada.