Wood has played an indispensable part in the rise of human civilization, evolution of modern plants and has cornerstone importance for the sustained long term health and stability of managed and unmanaged ecosystems. Despite its importance, the molecular mechanisms involved in wood formation are still poorly understood.Wood formation initiates in a lateral meristem known as vascular cambium which consists of meristem cells  organized in single-cell radial file that form continuous cylinder around the stem. Cambium initials divide to produce xylem, phloem, and ray mother cells that in turn undergo several rounds of divisions followed by differentiation into respective cell types. Because of their importance to regulation the quantity and quality of wood production these processes are of substantial theoretical and applied interest but are poorly understood and thus very difficult to manipulate. The progression from meristem to fully differentiated cells is a complex process requiring highly organized transition from different developmental states, most prominently, loosing the pluripotency of meristem cell and committing to a specific cell/tissue fate . Because of the importance of this transition plants establish developmental boundaries that insulate cells in different stages of this progression. We have recently shown that plant-specific transcription factors of the LATERAL ORGAN BOUNDARIES DOMAIN (LBD) family play key role in the establishment and function of these boundaries .PtaLBD1  with uncharacterized previously function in poplar and Arabidopsis, is primarily involved in differentiation of secondary phloem and ray cells. Transgenic gain and loss-of-function experiments demonstrated that PtLBD1 is a positive regulator of secondary phloem growth and development. Expression and localization experiments showed predominant expression in the phloem and localization of the transcript on the boundary between the differentiating phloem and the cambium zone. Genes encoding regulators of meristem identity genes like ARBORKNOX1 (ARK1) and ARBORKNOX2 (ARK2) were downregulated while key regulators of phloem initiation like ALTERED PHLOEM DEVELOPMENT (APL) gene was upregulated in the activation tagged mutant line. The phenotype, localization and misexpression of ARK1, ARK2 and APL genes indicate that LBD1 is a critical component in the establishment and function of the developmental boundary between the vascular cambium and the differentiating phloem. It shows that the boundary genes like LBD have dual function to repress meristem identity but promote proliferation and differentiation. We have also found that LBD1 is downregulated by auxin and is co-expressed with strong repressors of auxin response. Because auxin concentrations peak in the cambium and LBD1 is downregulated by auxin we hypothesize that part of the molecular mechanism that establishes the boundary is through auxin-mediated repression of LBD1 in the cambium zone.The discovery leading to the realization of the importance of LBD proteins in woody development was the identification and subsequent characterization of an activation tagged mutant that shows enhanced woody growth. We have found that the activation of a LBD encoding gene, Populus identified 57 members; microarray results display that four LBD genes  show predominant expression in stems undergoing wood production with two genes expressed in the phloem (PtaLBD1 and PtaLBD4) and two in the xylem . This suggests that a similar regulatory mechanism is in operation during xylem growth and differentiation.Vascular cambium of most extant plants is bifacial – producing xylem to the inside and phloem to the outside of the stem trunk. We then asked if the boundary on the xylem side of vascular cambium is organized and regulated in a similar manner. A broad preliminary survey of the LBD family in Vitis vinifera. There were 12 putative LBD1 orthologs. Vitis is vine and has a unique wood anatomy. Most notably, the rays are highly multiseriate and secondary phloem is well-developed with multiple growth rings. The intercalation of less-lignified tissues in the xylem of vines and lianas and proportionally more parenchyma tissues is an adaptive feature allowing more stem flexibility. The multiseriate rays and increased secondary phloem production in Vitis resembles the poplar transgenics with increased PtaLBD1 expression. Thus the putative increased LBD1 gene dosage in Vitis, well-corresponds to its wood anatomical features and suggests that LBD genes like LBD1 may have played important role in evolution of wood anatomy as an adaptive mechanism reflecting species biology and life habit.Our studies also shed light on possible mechanisms in the evolution of woodiness and wood anatomy. The LBD proteins are present in most genomes of the sequenced species from the plant kingdom with exceptions of algae. This suggests that the LBD gene family has evolved after the colonization of land plants. Comparative sequence analysis of putative LBD1 orthologs in several sequenced plant genomes, indicates a large and highly significant expansion of the LBD1 gene in Our findings have broad importance with respect to regulation and evolution of wood formation. They provide tools for manipulation of woody growth and development and provide clues for the mechanisms involved in evolution of wood anatomy with relation to plants’ biology and ecology.


Excess gestational weight gain (GWG) in pregnancy is a major clinical challenge affecting 55-75% of Canadian women who enter pregnancy overweight and about 40% women of normal weight. The adverse sequelae of excess GWG for both mother and child are well documented and include a number of adverse health outcomes , which impose substantive burden of our health system. The larger research program aims to conduct a randomized trial with a diet and exercise intervention for optimizing GWG. The project presented here is a preliminary phase in order to determine feasibility and patient preferences to the proposed intervention.This project uses a qualitative approach employing focus groups and interviews of participant women (pregnant or recently pregnant) and health care providers that aims to identify the preferred evidence-based strategies for women to effectively manage their GWG during and after pregnancy and how best to implement the selected intervention. Primary research question: What are the preferences of pregnant and post-partum women and their health providers for engaging in healthy eating and increased physical activity? Secondary questions include: What do pregnant or recently pregnant women and health providers identify as enablers or barriers that support or limit successful management of GWG? What are women’s and health providers’ perceptions of GWG in relation to their health and the health of the child? What approaches have women and health providers tried to manage excess GWG?Outcomes include an identified preferred diet and exercise intervention for the planned clinical trial and information, which enables refinement of a locally acceptable implementation plan for the intervention.Collectively information from women and service providers enabled a comprehensive understanding of barriers, enablers and opportunities for the successful implementation of an intervention for GWG management.


Action potentials (APs) generated and sustained by ionic currents flowing through neural cell’s membrane constitute the main way these cells communicate with each other. The most common, although not the only possible mechanism of generating APs, involves sodium influx that ensures cell depolarization and potassium efflux that ensures cell repolaroization. A sodium-potassium exchanger and leakage currents eliminate the ionic disturbance created by an AP. In a closely packed bundle of neuronal cells with fast diffusion of ionic species in the extracellular space (ECS) an AP generated in one axon could impact the excitability of nearby neurons. The ECS is similar in composition to the cerebrospinal fluid that baths the outer surface of the brain and is present in large internal cavities or ventricles and in the spinal canal. The ionic composition of ECS is mostly made of sodium and chloride dissolved in water with much smaller amounts of other substances, including potassium and calcium. Previous studies have considered the role of potassium in seizures by employing a computational model of potassium diffusion between periodically firing neurons . However


This correction will replace the previous correction made by PLOS ONE. There is more information that is missing from the Funding Disclosure.The first sentence in the Funding Statement should read:This research was supported in part by a National Geographic Society Discovery grant (awarded to DYY and DL), a SSHRC Partnership grant (awarded to DL), the Tula Foundation and Hakai Network for Coastal Peoples and Ecosystems.


An association of Paroxysmal Hemicrania (PH) with Trigeminal Neuralgia (TN) was described in eight patients ,2 and haLEPs study supported the diagnosis of TN idiopathic. It is still debated if the rare association of TN and PH is a new entity or two distinct disease. Further investigations by neuroimaging might be useful to clarify this issue and to better understand the pathophysiology of these entities .


The establishment of European Reference Networks as laid out under the Cross Border Health Care Directive (CBHCD) is a major opportunity for the rare disease community. There have been many successful networks for rare disease groups, but their establishment has been ad hoc and funding streams variable. Sustainability has been a major challenge. Although the assessment of the quality of these networks has not been systematic, nonetheless networks have succeeded in establishing important infrastructure including disease specific registries, shared tools such as tele-expertise and the production of disease specific guidelines and training pathways.Within the CBHCD it is envisaged that European Reference networks will be established, and these will not only relate to rare diseases. These networks will primarily link nationally designated centres of expertise. Within the EUCERD a process is being followed to inform the CBHCD committee on the specific issues relating to ERNs for rare diseases. These recommendations relate to areas of designation and governance, capacity building and resources to support ERNs and quality assurance.The recommendations will be discussed in a series of meetings in 2012, with the aim of producing a EUCERD recommendation on ERNs for rare diseases by the end of the year in line with the timeline of the cross border health care directive.


Rigid bracing has been the mainstay of orthotic intervention for children with neurological onset scoliosis. The use of rigid braces, however, often do not provide the expected outcomes clinicians are hoping for with Cobb angles curve increasing over time , linked This paper will discuss the use of dynamic elastomeric fabric orthoses (DEFO) in this client group and question whether rigid bracing is most appropriate for long term outcomes. It will also discuss whether waiting for the 25 degree Cobb threshold, before treatment, is prudent.This study will use single case presentations (n=5) to demonstrate the advantages of early intervention using both radiographs and pre and post intervention photographs to illustrate the outcomes possible. All of the children have neurological onset scoliosis and show short/ medium term outcomes.The use of DEFOs to control scoliosis has provided clinicians with an opportunity with which to reduce the number of children presenting for orthopaedic spinal surgery. Clinically the scoliosis clinic at the Norfolk & Norwich University Hospital has seen a declining number of children referred for scoliosis surgical management over the last ten years due to early intervention. The DEFO scoliosis suits appear to work by providing heightened proprioceptive input to the brain coupled with dynamic corrective forces to correct and re- align the spinal segments. The DEF


Since its publication by the European Society of Radiology (ESR) and the European Association of Nuclear Medicine (EANM), the Multimodality Imaging Training Curriculum has given rise to numerous discussions regarding its aims and applicability –4.Both societies therefore wish to clarify specifically the purpose and scope of the document. The aim of the Multimodality Imaging Training Curriculum as a joint European initiative is to advance the quality of performance and reporting of hybrid imaging by defining the scope of training for medical specialists in hybrid imaging. It outlines skills and knowledge requirements in nuclear medicine for those whose training background is in radiology and in radiology for those whose training background is in nuclear medicine.This training curriculum is intended to relate solely to the training of specialists in hybrid imaging from both radiology and nuclear medicine with the purpose of ensuring optimal use of this complex methodology for patient care. It by no means encompasses full training and/or qualification in imaging modalities unrelated to hybrid imaging techniques.


Familial Adenomatous Polyposis (FAP) is a well described autosomal dominant syndrome, whereby individuals develop multiple (up to thousands) of adenomatous polyps in the large bowel, conferring an extremely high risk of bowel cancer if left untreated.If the family specific mutation is known, genetic testing can be offered to at risk individuals to determine the need for endoscopic surveillance. Guidelines suggest starting endoscopic surveillance from the early teens. Most individuals with FAP undergo colectomy between the ages of 15 and 25 years [Recent studies have shown that many adults with FAP want their children to undergo genetic testing before the age of 12 years, the approximate age at which genetic testing is usually offered in Australia .Health professionals working in cancer genetics in Australia and New Zealand completed a web based survey aimed at examining their attitudes and experiences regarding genetic testing for young people at risk of FAP.Findings from the survey provide an insight into the views and practices of health professionals working in this area, including: the age at which they believe testing young people is most appropriate; their experiences regarding parental requests for testing of younger children; and whether the option of prenatal testing and pre-implantation genetic diagnosis is routinely discussed with individuals who have FAP and are also of child bearing age. These have important implications for clinical practice within the Australian cancer genetics community.


Epigenetic mechanisms have emerged as important contributors to cancer initiation and progression. DNA methylation of gene promoters has been extensively studied since the 1970s but the role of DNA methylation in the activity of distal regulatory elements (DREs) has only recently emerged. We have previously shown that tissue-specific differentially methylated regions overlap with DREs and that DNA methylation status correlates with their activity and the ability to bind transcription factors. We and others also demonstrated that such elements are dynamic and prone to demethylation. Our goal is to understand the role of DNA methylation and hydroxymethylation in the activity of DREs in cancer progression. OSCC, characterized by a double aetiology (exposure to carcinogens and HPV infection) and highly variable response to therapies, will be used as a model system.Herein, we present the preliminary data of genome-wide identification of DREs in HPV-positive and HPV-negative OSCC cell lines using Digital DNaseI-Seq method and the application of this method in detection of chromosomal alterations – insertions and deletions. Data obtained at this stage will be used to establish a new methodological workflow for the 5mC and 5hmC analysis at DREs using capture array for fragment enrichment followed by third generation sequencing.


The lack of a mechanism that aligns financial flows for global health research towards public health priorities limits the impact of health research on health and health equity. Collaborative groups of health research funders appear to be particularly well situated to ameliorate this situation and to initiate discussion on aid alignment for global health research. One such group is the Heads of International Research Organizations (HIROs), which brings together a large number of major government and philanthropic funders of biomedical research. Surprisingly, there is hardly any information publicly available on HIROs' objectives, or on how it aims to achieve more harmonization in the field of research for health. Greater transparency on HIROs' objectives and on its current efforts towards addressing the gap between global health research needs and investments would be desirable, given the enormous potential benefits of more coordination by this group. Such waThe Global Ministerial Forum on Research for Health in Bamako in 2008, in line with the Paris Declaration and the Accra Agenda for Action , recogniIn discussing the need for increased coordination among funders of research for health, it is important to consider what exactly needs to be coordinated. Recent positive developments among funders include the identification of common approaches to monitoring and evaluation and sharing research data ,18. Howe"Heads of International Research Organisations" OR "Heads of International Research Organizations" OR "Heads of International biomedical Research Organisations" OR "Heads of International biomedical Research Organizations" OR HIRO[Title/Abstract] OR HIROs[Title/Abstract] returns no relevant results. HIROs is not the only group where funders collaborate that is sparing with information. Recently, IHP+ was criticized for its lack of transparency [Since HIROs brings together the heads of major funders of biomedical research, it appears to be particularly well suited to give rise to the major changes in health research governance that are called for by the Bamako call to action. Unfortunately, HIROs has made little information available on its goals or on how it aims to achieve increased harmonization, alignment and coordination. An internet search reveals only websites noting that a meeting has taken place, and a search on PubMed for sparency . Individsparency .An initiative like the HIROs group is most welcome in the crowded field of global health research funders. It is surely one of the few groups that could initiate discussion on aid alignment for global health research. Given the enormous potential benefits of more coordination by this group, the contents of its discussions are of great interest to the global health research community. More transparency on HIROs' intentions for achieving increased coordination and on its current efforts towards addressing the gap between global health research needs and investments would therefore be desirable.The authors declare that they have no competing interests.


High-density microelectrode arrays (MEA) can measure neuronal activity in potentially thousands of units with a high spatial resolution . HoweverHere we estimate the quality of spike detection using correlations as an indicator to distinguish between neuronal activity and noise. First we use a threshold-based detection of putative spikes, with a deliberately low threshold to lower the number of undetected spikes. We estimate pairwise correlations between spike trains based on spike ranks rather than time in order to reduce the effects of nonstationarities in the recordings. We then assume that the frequency of spontaneous firing in the neurons is small compared to the evoked firing and check for each detected spike whether we can find correlated units which are active within a short interval around its spike time. For each unit, we compare the relative frequency of such correlated spikes to the frequency that would be obtained by doing the same analysis with a Poisson spike train.This yields a per unit estimate of the fraction of putatively falsely detected spikes and we validate the procedure using shuffled data and recordings of an empty MEA (see Figure


The 2008–2012 French Alzheimer plan is marked by the experimental implementation of “Homes for Integration and Autonomy for Alzheimer patients” with implementation of intensive case management process for people in complex situation. In 17 experimental sites, teams of case managers (CMs) have been implemented with a total of 67 case managers for performing an intensive case management.We conducted a qualitative study to develop a full understanding concerning the implementation of the case management process and the links with the interdisciplinary approach. Focus groups were conducted in 2010 to explore the perceptions of case managers six months after their recruitment.Interdisciplinary approach inside the case managers’ team has been rapidly constructed to resolve the complex situations, homogenize practices and help to create the new competency. Multidisciplinary and proximity team, common training and difficulties to get the good fit with professionals increased the interdisciplinary approach inside the case managers’ team. Interdisciplinary approach between case managers and clinical professionals was few implemented because of the high level of fragmentation and lack of case managers legitimacy.Implementation of intensive case management in an innovative integrated services delivery showed a stronger interdisciplinary approach between case managers compared to with clinical professionals.


Infections with the hepatitis B virus (HBV) are one of the major global public health problems. HBV has been categorized into different genotypes and subgenotypes that are distributed distinctively around the world. These classifications provide important information as the genotypes differ with respect to the clinical course of disease as well as in their response to antiviral therapy, and subgenotyping allows relevant conclusions about transmission routes, global or local spreading of infections or phylogenetic relations between viral strains . SeveralThe latest of these studies (published in 2012) investigated HBV genotypes and subgenotypes among patients living in the Eastern Black Sea region of Turkey . The aut


To the Editor,The article by E. Yorgancilar et al.  presentsIn connection with the article let us ask some questions to the authors: Were all of the patients operated on primarily? Why were the extradural abscesses and the temporal lobe abscesses not evacuated during the mastoid surgery? Temporal lobe abscesses may be evacuated during ear surgery (by puncture and aspiration). In this method of temporal lobe abscesses evacuation neuronavigation is a very serviceable tool. Neurosurgical approach to the cerebellar abscess and to the abscess located in occipital area is preferred. In patients with LST treatment consists of canal wall down mastoidectomy, delamination of dura and puncture of sigmoid sinus. When perisinus abscess is absent and a patient does not present symptoms of sepsis the clot is not removed from sigmoid sinus . In pres


Hemodynamic single use devices (SUD) namely cardiac catheters are reused worldwide and in India, where cost and aggressive intervention take priority over infection prevention, is no exception. An important issue associated with the reprocessing of any SUD is the potential for subsequent transmission of infectious agents.The reprocessing and sterilization methodology of reuse of SUD is often left to the discretion of the nursing staff (the clinicians do not play any role).The concerned staff often put the process best they know or is passed on by the predecessors. Safety, sterility issues are overlooked.To evaluate reprocessing and sterilization methodology. To develop guidelines and oversee their implementations that result in standardized practices and improve the safety of hemodynamic device reuse.Infection Control team took over the responsibility of the process initially by a small pilot study. A robust cleaning and sterilization processes protocol based on basic microbiological principles was developed and tested for bacterial, viral and endotoxin reminants before using on patients. Initially twenty cardiac angiogram patients (consent was taken) were followed up for three months for any adverse events with reuse policy in place. Clinicians feedback was taken and modification made in the process at the end of study. It was extended it to a full fledged protocol and implemented.This system is in place for the past 5 years and there are no adverse events reported on follow up (over 8000 angiograms so far).The facility does 12 angiogram per day and reuse is 75%.The protocol implementation has resulted in determining the number of times each catheter can be reused. The process is continuously audited and compliance to the protocol is 100%.The steps for repossessing are easy, adaptable, outcome measurable, sustainable and cost effective in resource limited settings.SUD is reused rampantly. No standard guidelines are available .The reprocessing is left to the staff who are ill informed of the consequences of reuse. The reprocessing should be based on sound microbiological and infection prevention principles and implementable .Frequent audit and follow up of patients is essential.None declared.


Sir,It is well known that contamination of the anaesthesia work area with potential bacterial pathogens and blood occurs intraoperatively followinWe propose the use of the plastic cover of the disposable PVC endotracheal tube to keep the contaminated laryngoscope blade to avoid soiling the top of the anaesthesia machine and work area. The laryngoscope blade can easily be kept inside this plastic cover which had been opened before intubation . The conThe complex intraoperative environment has been theoretically associated with the development of nosocomial infections and may contribute to the emerging pattern of increasing bacterial resistance in the hospital setting. Currently, there is no consensus regarding a satisfactory method for the routine cleaning, disinfection and sterilization of laryngoscope blades and handles. It has been shown that 33% of anaesthesia work surfaces Tobin MJOur method of safeguarding the anaesthesia work area from soiling with the contaminated laryngoscope blade is very simple, does not involve any extra expenditure and has the potential to reduce iatrogenic transmission of infection in the perioperative setting.


Two institutions that provided for payment of the publication charges for the article- a funding organization and university with which authors are affiliated that disbursed the funding- were incorrectly omitted from the funding statement. The Funding Statement should read: "The article processing charge was funded by the German Research Foundation (DFG) and the Albert Ludwigs University Freiburg in the funding programme Open Access Publishing."


To determine whether the pattern of late presentation noted previously in 2007 and 2008 in all patients newly diagnosed with HIV in our regional unit  has decrA retrospective case-note audit was undertaken in the ID/GUM clinics for all patients who were newly diagnosed with HIV in 2009. Patients were characterised as late presenters if they presented with a CD4 count of less than 200 or an AIDS defining illness. Medical records were reviewed to determine whether the patients had previously been diagnosed with a clinical indicator disease as defined by the UK National HIV Testing Guidelines, 2008, which might have facilitated earlier diagnosis of HIV. These 2009 data were compared with previous 2007 and 2008 data.See table 1Significant numbers of patients  still present with advanced HIV disease in the North East of England in 2009 despite the publications of the National UK Testing Guidelines in 2008. The numbers of late presenters have not changed as compared to 2007 and 2008. This is despite that a large proportion having had previous indicator diseases that should have prompt clinicians to test for HIV. Further education and awareness of the UK National Testing Guidelines 2008 should be encouraged if this burden of late presenters is to be reduced.


The vertebrate retina has a very high dynamic range. This is due to the concerted action of its diverse cell types. Ganglion cells, which are the output cells of the retina, have to preserve this high dynamic range to convey it to higher brain areas. Experimental evidence shows that the firing response of ganglion cells is strongly correlated with their total dendritic area and only weakly correlated with their dendritic branching complexity. On the other hand, theoretical studies with simple neuron models claim that active and large dendritic trees enhance the dynamic range of single neurons. Theoretical models also claim that electrical coupling between ganglion cells via gap junctions enhances their collective dynamic range. In this work we use morphologically reconstructed multi-compartmental ganglion cell models to perform two studies. In the first study we investigate the relationship between single ganglion cell dynamic range and number of dendritic branches/total dendritic area for both active and passive dendrites. Our results support the claim that large and active dendrites enhance the dynamic range of a single ganglion cell and show that total dendritic area has stronger correlation with dynamic range than with number of dendritic branches. In the second study we investigate the dynamic range of a square array of ganglion cells with passive or active dendritic trees coupled with each other via dendrodendritic gap junctions. Our results suggest that electrical coupling between active dendritic trees enhances the dynamic range of the ganglion cell array in comparison with both the uncoupled case and the coupled case with cells with passive dendrites. The results from our detailed computational modeling studies suggest that the key properties of the ganglion cells that endow them with a large dynamic range are large and active dendritic trees and electrical coupling via gap junctions. One of the many important features of the vertebrate retina is the capacity to respond to signals over a wide range of intensities with a dynamic range of several orders of magnitude spatially extended excitable systems whose nonlinear input-output transfer function endows the neuron with a large dynamic range. If this hypothesis is valid, most cells of the vertebrate retina do not benefit from this property because they have simple dendritic structures. The possible exceptions are the ganglion and amacrine cells, which are the most complex cells of the retina and have relatively intricate dendritic arbors A single neuron characteristic, which is claimed to be fundamental for enhancing the neuronal dynamic range in general is the size and complexity of the neuronal dendritic tree with active conductances versus stimulus current (F–I) curve. These studies found strong correlations between the total somatic plus dendritic surface area of the cell and its electrophysiological class and F-I curve.There is evidence in favor of a relationship between properties of ganglion cell dendritic trees and their firing behavior, however not exactly as predicted by the above theory. Computational studies with morphologically reconstructed models of ganglion cells of the salamander retina From the point of view of network properties, a mechanism that may contribute to enhance the collective dynamic range of the network is electrical coupling between cells via gap junctions Ganglion cells of the vertebrate retina are coupled by electrical synapses via dendrodendritic gap junctions In this work we use morphologically reconstructed, multicompartmental models of ganglion cells of the vertebrate retina with realistic distributions of ion channels to perform two computational studies on the dynamic range of ganglion cells. The first is concerned with the dynamic range of isolated ganglion cells and its objective is to compare the effects of active and passive dendrites on the cells’ dynamic range and to assess what measure of size of dendritic arbor correlates better with the ganglion cell dynamic range: total dendritic surface area or number of dendritic branches. We measure the correlation between dynamic range and these two measures of dendritic tree size for a population of cell models with either passive or active dendrites. Our results show that active dendrites enhance the dynamic range in comparison with passive dendrites and when dendrites are active the dynamic range of isolated ganglion cells is positively correlated with either measure of dendritic tree size, though more strongly with total dendritic surface area than with number of dendritic branches.The second study is aimed at assessing the role of ganglion cell coupling by gap junctions on the dynamic range of the ganglion cell population. We construct a network of ganglion cells by coupling them via dendrodendritic gap junctions with realistic conductance values. The network simulates a small area of the ganglion cell layer. We consider different configurations of the network, with passive/active dendrites and different values of the electrical synapse conductance. The dynamic range of the network is measured either directly, by the average firing rate of all neurons in the network, or indirectly, by the firing rate of a lateral geniculate nucleus pyramidal neuron model coupled by chemical synapses to all ganglion cells in the network. As far as we know, this is the first computational investigation of the dynamic range of a neural cell layer using reconstructed neurons with full morphologies and realistic ion channel distributions. Our results show unequivocally that electrical coupling, especially when dendrites are active, increases the dynamic range in comparison with the uncoupled case.Our two results put together imply that to maximize the dynamic range of a population of vertebrate ganglion cells the best configuration would be cells with large and active dendritic trees coupled by gap junctions.We worked with a sample of 20 morphologically and biophysically detailed models of ganglion cells from the tiger salamander (for details see Methods). Cells belonged to four different morphological groups (5 per group), based on the size and complexity of their dendritic trees 1 to 2.103 pA in steps of 10 pA. In The dynamic range of each cell in the sample was determined from its F-I curve (see Methods). To obtain the F-I curve of a cell model, we submitted it to somatic step current injections ranging from 10The transition from tonic firing to rest observed in versus number of dendritic branches , the dynamic range is only marginally larger when the compartment is active in comparison with when the compartment is passive. However, for larger areas the behaviors of the cases diverge dramatically: the dynamic range for the active case constantly increases with area while the dynamic range for the passive case constantly decreases with area. The difference Γ between the dynamic ranges for the active and passive cases is shown in The results of this experiment are given in The second study was designed to assess the effect of electrical coupling between ganglion cells on the collective dynamic range of the cells. We simulated a 3×3 square array of ganglion cells coupled via dendrodendritic gap junctions as shown in 1 to 105 pA. This central neuron excites the other neurons via gap junctions so that we can relate the steady state firing frequency of each one of the nine neurons in the array to the amplitude of the applied current input. In our experiments, step current inputs were applied to the central neuron of the array with amplitudes varying from 10Each coupled cell exhibits a F-I pattern similar to the one of the single cell in Although the enhancement was similar for the simulations with passive and active trees, the maximum dynamic range was obtained for the coupled array of ganglion cells with active dendrites . This ref given in f was calculated as IA/IP, where IA is the maximum current amplitude for the indicated cell of the coupled array with active dendrites and IP is the maximum current amplitude for the same cell with passive dendrites. The calculated value of f = 2.94 shows that when cells in the coupled array have active dendrites the chosen cell can respond to inputs almost 3 times higher before saturation when compared to the same cell in the same coupled array but with all cells in the array with passive dendrites.A quantitative estimate of the contribution of active dendrites to the further enhancement of the dynamic range of a cell in the coupled array is provided by factor An indirect way to assess the dynamic range of the coupled array of ganglion cells is by measuring the dynamic range of the pyramidal neuron that receives input from them. The main result of our simulation studies with morphologically reconstructed ganglion cell models is that active dendrites enhance the dynamic range of the cells. The other two important results are that (1) for isolated ganglion cells, the dynamic range has positive and significant correlation with the size of the active dendritic tree , and (2) by coupling ganglion cells via gap junctions the dynamic range of the coupled cells is further enhanced, being greater than the average dynamic range of the individual cells.Why a cell with active dendrites has a larger dynamic range than a morphologically similar cell with passive dendrites? Passive dendrites act as current sinks. Current injected at the soma escapes to dendrites reducing the efficiency of the input current in making the cell fire. Active dendrites, on the other hand, allow soma-generated spikes to propagate into the dendritic tree. These in turn generate dendritic spikes, which interact nonlinearly across the dendritic arbor leading to creation and annihilation of spikes and the consequent enhancement of the cell’s dynamic range This explains the lower values of dynamic range for ganglion cells with passive dendrites in comparison with ganglion cells with active dendrites. It also explains the positive correlation between dynamic range and size of the dendritic tree for cells with active dendrites and the negative correlation between dynamic range and size of the dendritic tree for cells with passive dendrites. Since passive dendrites act as current sinks, the larger the dendritic tree, the more space for current to sink. On the other hand, larger dendritic trees have more active ion channels to support spike creation and summation.per area rather than per dendrite.And why dendritic surface area correlates better with dynamic range than with number of dendritic branches? The stronger correlation of dynamic range with dendritic surface area than with number of dendritic branches means that dendritic surface area is a better predictor of dynamic range than number of dendritic branches. As commented above, the critical factor for the enhancement of the dynamic range of a cell is to have active ion channels distributed over its dendrites. So, surface area correlates better with dynamic range simply because it is a better estimator of the number of ion channels in a dendritic tree than number of dendrites. This is because the number of ion channels in a dendritic tree is determined by channel densities A demonstration that the key factor to enhance the dynamic range of a ganglion cell is the number of active ion channels in its dendrites is given by the results shown in Our results show that when ganglion cells are coupled by gap junctions their dynamic range is much higher than the average dynamic range of isolated ganglion cells. Even ganglion cells with passive dendrites, when coupled by gap junctions, have a larger dynamic range than isolated ganglion cells with active dendrites. The average dynamic range of these latter is 11.30 dB and the dynamic range of the former is 31.9 dB. When the coupled cells have active dendrites, the dynamic range of the array is a little higher: 34.7 dB.Why coupled cells with passive dendrites have a larger dynamic range than isolated ganglion cells with active dendrites? The reason for this is that dendrodendritic coupling by gap junctions interlinks the somata of the cells, which have active ion channels, transforming the system into a spatially extended excitable medium. The mechanism responsible for the enhancement of the dynamic range of the coupled ganglion cells with passive dendrites is, therefore, the same one responsible for the enhancement of the dynamic range of an isolated ganglion cell with active dendrites, namely nonlinear summation of spikes Based on our results on the dynamic range of coupled ganglion cells we can make two predictions: (1) blockade of gap junctional coupling of ganglion cells in the vertebrate retina should strongly reduce (approximately by 40%) the output dynamic range of the retina; and (2) selective suppression of dendritic (but not somatic) spiking of coupled ganglion cells in the vertebrate retina should reduce the output dynamic range of the retina by a much smaller factor (approximately 9%). These reductions could be verified by simultaneous recording from lateral geniculate nucleus pyramidal cells.In a previous work, we used a detailed model of the scotopic pathways that convey information from rods to a single ganglion cell of the vertebrate retina to study the effect of coupling by gap junction at the first stages of these pathways on the dynamic range of the ganglion cell We further predict, based on our results, that it is unlikely that any type of ganglion cell would have a passive tree or a very low channel density at the dendrites. We also predict that, if there are uncoupled ganglion cells in the retina, these are distributed over the retina so that cells with large dendritic trees (which imply large dynamic ranges) are able to integrate signals from circuits mediated by rods and cones responding to dim and bright light conditions. On the other hand, ganglion cells with small dendritic trees should be specialized to photopic or scotopic conditions. These predictions could be experimentally confirmed in the future with a detailed study on the distribution of morphologically distinct ganglion cells over the vertebrate retina.Future investigations can provide a better understanding on the roles of cell connectivity and membrane properties on the dynamic range of the retina. The model can be further improved with a more realistic synaptic input distribution over the dendrites of ganglion cells and also extended to include the main circuits involved with dim and bright light processing in the retina.Ambystoma tigrinum) retina http://senselab.med.yale.edu/modelDB). The reconstructed neurons were classified into four groups: medium-complex (MC), medium-simple (MS), small-complex (SC), and small-simple (SS) We worked with a sample of 20 morphologically reconstructed, three-dimensional ganglion cell models from the tiger salamander (A), one calcium-dependent channel (KCa). The dynamics and parameters of the calcium current were able to fit the high-voltage activated component of the calcium current (L-type) described in a previous experimental work A channels have inactivation kinetics. The channel densities for each group of compartments are given in The same set of active ion channels were placed in all ganglion cell models. Each model has four voltage-dependent channels  was calculated as:Na and IK currents and the T-type calcium current. The values of the parameters used to model these channels can be seen at the original work The single compartment model of a lateral geniculate nucleus pyramidal neuron used to obtain We used experimental evidence of dendrodendritic bidirectional gap junctions connecting ganglion cells tbinding  = 0.2 ms, tunbinding  = 1.1 ms), activated by square-wave transmitter pulses of amplitude 1 mM and duration 0.3 ms The excitatory chemical synapse between the axon of a ganglion cell and the LGN pyramidal cell was modeled by a closed/open gating scheme (The network model consisted of 9 ganglion cells and a single LGN pyramidal cell. The ganglion cells were arranged in a 3×3 square grid and connected by gap junctions as shown in 1 pA to 105 pA separated by steps of 10 pA. We consider 0.3 seconds a period sufficiently long for a reliable estimate of the ganglion cells’ firing frequency and to obtain the dynamic range of the ganglion cells and the pyramidal neuron. The simulations were performed in NEURON 7.1 To obtain the average response of the ganglion cells and the pyramidal neuron for a given amplitude of current clamp, we stimulated the network with the current for 0.3 seconds and counted the number of spikes during this period. We used current amplitudes in the range from 10


The standardised mortality ratio (SMR) is a key parameter by which ICUs quantify their performance. We report the effect of increased ICU consultant numbers on mortality and SMR in a central London teaching hospital.The study was registered with the Clinical Audit Support System. Data were collected prospectively from March 2005 to date by a dedicated audit team and were analysed as part of routine audit.Table In this study we describe the remarkable reduction in both mortality and SMR that has occurred in the general ICU at King's College Hospital over the past 5 years. The improvement in outcomes was associated with a quadrupling of ICU consultant numbers. We hypothesize that this increase in intensivist numbers allowed the reinforcement of a closed model of ICU care. We are now further analysing these data to search for quantitative improvements in surrogate markers of quality of care over the same time frame.


Most of our cognitive life depends on our brain's ability to generate internal representations of the external world. The hippocampus is a brain structure that supports the formation of internal representations of the spatial environment  could suggest that once sequentially active cell assemblies are bound into a temporal sequence during theta they no longer need the theta oscillation for them to be expressed at a later time. This scenario would be consistent with the third prediction that posits that compressed temporal sequences of novel place cells should not be expressed before the novel spatial experience. However, temporal firing sequences reflecting the future order of place cell firing and future novel trajectories can be expressed during sharp-wave ripple epochs occurring during sleep or rest in naïve animals before they had any experience on long linear tracks (Dragoi and Tonegawa, We explored the role of synaptic plasticity of intrinsic hippocampal circuitry in the internal organization of the hippocampal network in sequential cellular assemblies (Dragoi et al., The existence of preconfigured cellular assemblies and the phenomenon of preplay lead to a novel concept that an animal's encounter with a novel spatial experience is encoded in the hippocampus, in part using blocks of pre-made cellular firing sequences rather than creating all the sequences de novo in response to the external cues. This mechanism may contribute to the role of the hippocampus in prospective coding (Schacter et al.,


HIV drug resistance has proved to one of the greatest challenges to effective and durable viral suppression. Selection of drug resistance mutations and widespread cross-resistance between agents of a class are a main obstacle when administering antiretroviral agents in clinical practice. This has been perhaps the greatest barrier to incorporating HIV care in to routine medical management administered by general practitioners. As opposed to many other disease states where the development of effective therapy allowed for simple widespread use as part of general care, HIV drug resistance has mandated cumbersome, resource consuming and demanding medical practice from both clinicians and even more so patients. Extremely demanding lifelong drug taking behavior by patients, high level clinician knowledge and expertise; and expensive monitoring technologies are all required for durable clinical benefit from antiretroviral therapy due to resistance.But knowledge and understanding of drug resistance has also brought great improvement in HIV care. Technologies to detect and identify resistance as well as rapid and reasonably accurate interpretation have been developed and refined. A far greater understanding of resistance and its consequences by providers and patients have molded our highly effective modern care. Development of improved drugs including those with unique mechanisms has greatly benefited from our growing knowledge.As we move forward to the next decade of HIV care, we need to revisit how we relate to and address HIV drug resistance. Old assumptions need to be challenged; data needs to be critically evaluated considering our new and improved drugs, and widespread treatment of patients in resource limited settings need to be specifically prioritized as challenges may not be identical. How should our much improved (but expensive) resistance assays be used? To what degree do we need to continue to closely monitor HIV drug resistance and in what settings? Is resistance still a high priority when designing optimal drug combinations for our patients – those naive and those drug-experienced? How can we minimize the barrier resistance presents to more simplified and widespread antiretroviral therapy? These are important issues we must address to guarantee the best care for the most patients in coming years.


The authors would like to make the following corrections to their published paper:50 fold changes for the NAI-resistant viruses reported in There was an error in calculation of ICWe apologize for any inconvenience caused to the readers.


We alsoet al.  . In thiThe autopsy lungs of severe asthmatics and controls were examined by immunohistochemistry to reveal the lymphatics and morphometry using an image analyzer system was applied to compare the distribution of airway lymphatics in the same level of airways among these asthmatics and controls. We also estimated the degree of airway smooth muscles and fibrosis around the airways which would interrupt or disrupt airway lymphatics.The total area of airway lymphatics in each lung was found to be positively correlated with the airway radius. The distribution areas of lymphatics in larger airways of both types of asthmatics were significantly decreased than controls, and the severe asthmatics with increased muscle layers only in larger airways were found to have less lymphatics in these airways than the other group of severe asthmatics with increased smooth muscles in whole airways. The lymphatics around smaller airways were also reduced in both phenotypes of asthmatics without statistic difference. The airway lymphatics of these severe asthmatics were interrupted by both thickened muscle bundle layers and fibrotic tissues developed in the airway walls.These results indicate disrupted airway lymphatics as a novel cause of mucosal edema in severe asthmatics.


The implementation of National Digital Health project get a high opinion from leaders at all levels and domestic and foreign experts, its research get a tremendous impact on construction of health information, play a technical supporting role of boosting health care reform and servicing people health, and make important significance to promote the development of Chinese public health care.


The Building Bridges initiative was designed to promote positive cross-cultural interactions among young people and improve the mental health of migrant and refugee populations by addressing race-based discrimination. The goal of the evaluation was to build the evidence and knowledge base for promoting mental health and wellbeing by reducing discrimination through promoting cooperative intercultural contact. The design of the evaluation was multi-level with data collected at the individual, organisational and community levels to evaluate change associated with program participation and examine barriers and enablers to implementation.The evaluation used a before and after design. It examined characteristics of participants, the environment for intercultural contact , attitudes to people from other cultures and Basic Psychological Needs . Both quBuilding Bridges was effective in reaching children and young people who were affected by discrimination and for whom improving intercultural relations was a priority. Building Bridges projects all scored highly on their ability to provide an environment for effective intercultural contact. The results suggest that performance against the Equal treatment and Shared goals/Co-operation is important for how participants feel about themselves and others. Institutional Support for intercultural contact may be critical for translating these gains into meaningful changes in intercultural relationships.The analysis of the impact of the intervention showed that attitudes to intercultural relationships remained the same or improved marginally for people with nationalities other than Australian over the course of the intervention. However, attitudes to intercultural relationships declined for people with Australian ethnicity bringing them in closer alignment with the attitudes of participants with nationalities other than Australian. There was also evidence of positive effects on mental wellbeing with particular improvements for people with ethnicities other than Australian. Overall, the results suggest of a shift in power relations between the populations involved which had positive health effects.Overall, Building Bridges is a pilot program that has benefited the individuals, organisations and community involved and has yielded important learnings about the implementation of pro-diversity programs. The evaluation findings challenged assumptions about the impact of living in a multicultural society on intercultural relations and make a significant contribution to our understanding of pro-diversity interventions.


To the Editor: We have critically read the brief report by Dr. Taha et alUnfortunately, this study recruited only male medical students and hence lost an opportunity to explore simultaneously the water pipe smoking behavior of female medical students. This is a major caveat because a comparative study involving both genders might have substantiated or refuted already emerging findings; one of them is that water pipe smoking is more common among females. Another limitation of this study is that the authors designed a new questionnaire rather than using one of the most relevant standardized questionnaires developed jointly by international health organizations, including the World Health Organization, the Canadian Public Health Association and the US Centers for Disease Control and Prevention. In doing so, the authors fell short of assessing the specific and relative social and cultural beliefs of male versus female students in Saudi Arabia, as medical students in medical colleges often hail from different regions. Furthermore, this study did not add anything major or new to the existing literature on shisha smoking. However, one finding and related explanation is noteworthy: mothers of water pipe smokers had an advanced education compared with mothers of those of nonsmokers. According to this study this result was speculatively attributed to two factors including shisha smoking as a prestige behavior and an indication of a modern standard of living. However, the commentators feel that these explanations might not be true because mothers were not asked about the explanations underlying the linkage between their higher education and shisha smoking. This finding needs further study. There might be more plausible explanations: shisha smoking in modern times is merely a continuation of a very old traditional behavior of the Eastern world and it may not be a prestigious behavior at all; rather it may reflect low status. A study that recruits a larger sample representative of all Saudi medical colleges might truly shed light on this finding and a more detailed explanation must be included in the measurement tools.4Finally, shisha smoking is a global health problem of the young population and needs effective preventive strategies across the world, including health warning labels on water pipe tobacco products and related accessories.The author of the original report declined to respond


To review existing methods to specify condition specific prevalence of and experience of the use of CAM in children in the US and begin to specify a strategic data plan to support evaluation of pediatric integrative medicine.Qualitative  and quantitative methods were used to evaluate the National Health Interview Survey’s Children’s CAM Supplement (2007), the Medical Expenditures Panel Survey (2008) and the National Survey of Children with Special Health Care Needs (2009/10), and to compare findings and specify strengths and weaknesses of each.Using the NHIS Child CAM Supplement method for asking about reasons for the use of CAM in children, we would conclude that fewer than 15% of all children using CAM do so for specific health conditions. However, over 91.7% of all child CAM users had parents who indicated in the larger NHIS that their child had one or more of 59 health problems or conditions assessed and over half of these had 3 or more health conditions. Nearly 40% of all child CAM users met criteria for having a special health care need. Linkage of NHIS and MEPS datasets result in 2411 cases of data - insufficient to validly explore the many condition specific patterns and associations critical to better understanding the need for and impact of integrative medicine for children. NS-CSHCN findings reveal similar overall prevalence and patterns of use and offers alternative methods for consideration.NHIS Child CAM Supplement methods are not valid for assessing CAM use among children with specific health conditions. Alignment with methods used in conventional medical care will enable comparisons between and relationships among CAM and conventional medicine use in the care of children’s health conditions. A strategic approach to ensuring sufficient and valid data are collected across all national surveys is indicated.


Participant recruitment is understood to be one of the most difficult aspects of the research process. Researchers are now devoting increasing amounts of time and resources to understand how participants decide to take part in research and what researchers can do to make their work appeal to potential participants. The purpose of the study is to assess the problems experienced by researchers in Northern Ireland when recruiting human participants into trials and studies and to gain insight into how researchers handle and overcome these issues. The main research question being addressed by this research is to develop an understanding of the problems experienced by staff when recruiting human participants to research projects. Methods used to increase study recruitment were also examined. The participants in this research are investigators and other associated staff on research studies based in Northern Ireland. Potential participants were identified through contacts with research active organizations such as the academic researchers in Queen’s University Belfast and research physicians and clinical trialists employed by the Belfast Health and Social Care Trust. Each organization forwarded on the survey request via email or newsletters. Researchers willing to take part accessed the questionnaire through the Survey Monkey website. This study utilised a cross-sectional questionnaire design.


Secondary growth and the development of woody tissue is a key process in the formation of woody biomass. The gene family of Class III HDZip genes has been shown in the herbaceous Arabidopsis model to play a central role in regulating polarity and vascular development. While Arabidopis is a poor model for investigating processes of wood formation, in this project all poplar Class III HDZip genes were cloned and expressed in hybrid aspen as a tree model system. To circumvent an endogenous regulation mechanism involving microRNAs the sequences were also mutated to render them microRNA resistant. Lines expressing the mutated Poplar ortholog of the Arabidopsis Revoluta gene (Populus Revoluta PRE) show a spectacular phenotype with stunted growth, radialized and rolled leaves, and a double and at times triplication or quadruple layer of the xylem, suggesting the formation of multiple layers of cambium. ClassIII HDZip genes have thus been shown to be crucial for the formation of lignified tissue in trees.


The recently occurred pandemic H1N1 has given lessons on the significance of a multisectorial approach in developing mechanism for responses and preparedness against the spread of communicable diseases. This approach can expand beyond the administrative jurisdiction of a country when there is transboundary movement of diseases when measures taken require cross-border coordination. In this notion, regional integration appears to be a mechanism to address this challenge.The Asia-Europe Foundation (ASEF) Network for Public Health launched in May 2009 was established as part of the wider initiative of Asia-Europe Meeting (ASEM) Foreign Ministers’ Meeting in combating possible human influenza pandemic. Financially supported by the Government of Japan for a period of 5 years (2009-2013), the ASEF Network is part of the wider ASEM Initiative for the Rapid Containment of Pandemic Influenza which also includes a regional stockpile.The paper will highlight the three thematic working groups of the ASEF Network and their activities for the past two years and how these activities have contributed in building bridges among public health stakeholders in Asia and Europe.


Whereas astrocytes have been in the limelight of scientific interest in brain energy metabolism for a while, oligodendrocytes are still waiting for a place on the metabolic stage. We propose to term the interaction of oligodendrocytes with astrocytes and neurons: NOA (neuron–oligodendrocyte–astrocyte) interactions. One of the reasons to find out more about metabolic interactions between oligodendrocytes, neurons, and astrocytes is to establish markers of healthy oligodendrocyte metabolism that could be used for the diagnosis and assessment of white matter disease. The vesicular release of glutamate in the white matter has received considerable attention in the past. Oligodendrocyte lineage cells express glutamate receptors and glutamate toxicity has been implicated in diseases affecting oligodendrocytes such as hypoxic-ischaemic encephalopathy, inflammatory diseases and trauma. As oligodendrocyte precursor cells vividly react to injury it is also important to establish whether cells recruited into damaged areas are able to regenerate lost myelin sheaths or whether astrocytic scarring occurs. It is therefore important to consider metabolic aspects of astrocytes and oligodendrocytes separately. The present review summarizes the limited evidence available on metabolic cycles in oligodendrocytes and so hopes to stimulate further research interests in this important field. The body of research from the last century has established the present view of contiguous neurons in continuous, dynamic interaction with several types of glial cells . The interactions between neurons and astrocytes characterized by the glutamate–glutamine(–GABA) shuttle have received considerable attention since its discovery in the 1970s  an increase in MCT1 was observed in the spinal cord  described above be extended to a tri-cellular one including oligodendrocytes? The lack of knowledge available on the metabolic role of oligodendrocytes in the brain was highlighted recently with two publications in Nature  has a tri-cellular compartmentation , NAA is then assembled and released from neurons and hydrolyzed to acetate and aspartate −1  for the synthesis of oxaloacetate? Aspartate is an essential member of the malate aspartate shuttle which is the major shuttle for reducing equivalents from NADH from glycolysis into the mitochondria  interactions. Well-designed experiments are necessary to find answers to these and other questions concerning the referred metabolic pathways and cycles in oligodendrocytes.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.


Clients across Hunter New England Area Health Service (HNEAHS) with complex diabetes foot complications traditionally had to travel to Newcastle to access multidisciplinary high risk foot services; with some travelling up to five hours each way to attend the High Risk Foot Clinic in Newcastle. Ideally rural clients should be able to access multidisciplinary high risk foot services close to their home.A six-month pilot Telehealth High Risk Foot Clinic was established between Newcastle and Tamworth, with clinicians in Newcastle providing Telehealth multidisciplinary input for clients attending the Tamworth Podiatry Clinic.Over the six month pilot phase (February – August 2010) a total of eight clients were seen through the HNEAHS Telehealth High Risk Foot Clinic; seven presented with foot wounds and one presented with an acute Charcot Neuroarthropathy. Two clients (25%) refused gold standard treatment; one was subsequently discharged from the High Risk Foot Clinic and the other did not return for follow-up treatment. Of the remaining six clients, four (75%) achieved successful resolution of their presenting complaint. Clients surveyed in the evaluation phase indicated that they would prefer to attend the Telehealth clinic at Tamworth as it is closer to home, meaning less travel time and expense as well as reducing the impact on their work and/or family commitments. None of the clients felt unsatisfied in any way about the Telehealth model and all felt very satisfied by the impact that the clinic made on their quality of life. A cost analysis of the pilot model showed that this type of service is of cost benefit and has the potential to prevent lower limb amputations in high risk clients residing in rural areas.The pilot clinic resulted in many positive benefits to high risk foot clients living in rural areas. Good clinical outcomes were achieved, the client’s quality of life was improved and cost benefits were attained. Also of note, were the strong relationships that were formed between Newcastle and Tamworth; resulting in rural clinicians being empowered with knowledge of the management of the high risk foot.


Patients with Complex Regional Pain Syndrome (CRPS) experience distressing changes in body perception. However representing body perception is a challenge. A digital media tool for communicating body perception disturbances was developed. A proof of concept study evaluating the acceptability of the application for patients to communicate their body perception is reported in this methods paper. Thirteen CRPS participants admitted to a 2-week inpatient rehabilitation program used the application in a consultation with a research nurse. Audio recordings were made of the process and a structured questionnaire was administered to capture experiences of using the tool. Participants produced powerful images of disturbances in their body perception. All reported the tool acceptable for communicating their body perception. Participants described the positive impact of now seeing an image they had previously only imagined and could now convey to others. The application has provided a novel way for communicating perceptions that are otherwise difficult to convey. Changes in body perception can occur following peripheral injuries, or central nervous system damage  the ability of the body perception tool to represent participant’s experience, (ii) their reactions to using the tool, (iii) limitations and aspects for refinement.Reflecting the CRPS population, participants were predominantly female 10 female). Ages ranged from 24 to 64 years (median 54), and CRPS duration ranged from 6 months to 7 years (median 14 months). Ten had an upper limb affected and three a lower limb (one participant had both upper and lower leg on one side affected). The characteristics of each participant are listed in Table 0 female.The participants produced powerful images of the disturbances in body perception they experienced. Some examples supported with quotes of participants’ verbal descriptions are given in Figure Alterations in scaling were common with participants feeling that limb parts were either larger or smaller than normal and these perceptions were illustrated on the computer model  in many cases. This was because he wanted responses first hand and initially it was to help train the nurse in using the tool. This lack of independence in the evaluation could have led participants to be more positive about the application than they might otherwise have been. However both the nurse and the software developer stressed their desire for the participant’s honest opinions in order to establish the acceptability of the body perception application to patients and for identifying aspects that needed to be changed.Areas for improvement to the application were identified, for example animation of perceived involuntary movements and creating more sophisticated depictions of sensation. However future use of the application needs to be considered before adding greater levels of detail and complexity. With increasing use of telemedicine, future versions of the application could be made to enable the software to be used by patients independently of clinicians in their own homes over the internet. The participants tested seemed to like using the application with the nurse; perhaps because it was new to them and may have appeared complicated. One of the participants even expressed the view that she was likely to have been less honest if she had used it on her own. However with the increasing use of finger activated tablets development of the tool using touch screen operation that is intuitive and user-friendly is important for its future development. Manipulation using finger drags and taps to turn the avatar, enlarge and shrink parts, and drop on textures and color will need to be robust for use on these smaller screens. The operations will have to be easy to complete with the non-dominant hand, since in some individuals their condition will have affected dexterity in their preferred hand. Further careful evaluation of independent usability and comparison of results between methods of delivery will be needed to determine reliability.There is also further work to do in exploring the best form of the avatar for patients to represent their disturbed body perception. Previous research using body image morphing techniques with fit healthy people and with obese people has indicated that body perception is influenced by the form of the image presented (Stewart et al., Further development and evaluation is in progress to determine the use of the body perception application with people with stroke. A significant prevalence of phantom limb in the form of postural illusions of limb position has been found in people with stroke (Antoniello et al., Since there is potential to “repair” distressing body perception using rehabilitation interventions (Flor et al., Another potential function of the body perception application is to quantify changes in predominant features in response to treatment. Other investigators have taken measurements of scaling from photo software. Vector deviations of image manipulations of a patient’s representation, relative to a reference photograph, were obtained to measure perceived size changes of one side of his face (Rode et al., This proof of principle study has shown that the body perception tool provides a powerful vehicle for communicating and representing changes in body perception.We envisage that this tool could extend beyond being a very useful communication device between patients and clinicians and also become a meaningful process measure and an interactive tool for intervention.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.


DNA barcoding generates a unique identification tag for individual species based on the sequence of a short stretch of DNA. For this study we evaluated the potential of DNA barcoding methods for identification of medicinal plants using examples from the Lower Rio Grande Valley border region in Texas. Many plants that enter the supply chain are not evaluated for correct identification and better and faster methods are needed for identification of fragmented samples.We sequenced several genomic regions, both nuclear and chloroplast, in order to assess variability and ability to identify highly fragmented plant material or otherwise incomplete specimens. Unidentified samples were compared with data available in Genbank and with an extensive collection of known reference materials.We successfully used phylogenetic techniques for correct placement of the unidentified samples and potential applications for this method are discussed. We compare this method with the Genbank-BLAST search technique that is widely used for sequence matching.In conclusion, DNA barcoding can be effectively used as an identification method for medicinal plant preparations that allows fast and efficient control for distributors, provides information to customers, and, in case of a poisoning accident, might aide in determining correct treatment and countermeasures. Our studies also showed that comprehensive databases for reference materials need to be carefully assembled and curated to provide reliable information for comparisons. Currently existing databases do not fulfill this requirement leading to potential misidentifications.


Most studies have analyzed the factors affecting paternity insurance and dominance tenure separately. We use a long term data set on Alpine marmots to investigate the effect of the number of subordinate males on both paternity insurance and tenure of dominant males. We show that individuals which are unable to monopolize reproduction in their family groups in the presence of many subordinate males are likely to lose dominance the following year. We also report that dominant males lose body mass in the year they lose both paternity and dominance. Our results suggest that controlling many subordinate males is energetically costly for dominant males, and those unable to support this cost lose the control over both reproduction and dominance. A large number of subordinate males in social groups is therefore costly for dominant males in terms of fitness.Paternity insurance and dominance tenure length are two important components of male reproductive success, particularly in species where reproduction is highly skewed towards a few individuals. Identifying the factors affecting these two components is crucial to better understand the pattern of variation in reproductive success among males. In social species, the social context ( The number of offspring sired per year and the length of reproductive life are two major components of lifetime reproductive success The social context which dominant males have to cope with may be a key element of reproductive success. Subordinates within and outside the social unit compete with dominants both to reproduce and to reach dominance Suricata suricattaPapio cynocephalusMarmota marmotaMandrillus sphinxi.e. few subordinates), while males facing highly competitive situations (i.e. a large number of subordinates) should be unable to insure paternity and should lose their dominant status rapidly. In other words, the males which lose control over reproduction, due to challenging social conditions, will also lose dominance in their social group rather rapidly.To date, most studies have analyzed factors affecting paternity insurance and dominance tenure separately. As expected, dominants do lose paternity when they are confronted by a large number of subordinate males, for example in meerkats The mechanisms by which the number of subordinate males reduces the ability of the dominant male to secure paternity and to maintain dominance are not well understood. One possible explanation is that it may be energetically costly for dominant males to control potential competitors present in the social unit The Alpine marmot is a mammalian cooperative breeder, socially monogamous, which lives in family groups of 2 to 14 individuals comprising a dominant reproductive pair, mature and immature subordinates of both sexes and pups of the year Here we use a 18-year data set to (1) examine the effect of the number of potential competitors on the probability of losing both paternity and dominance in the male Alpine marmot; (2) test the prediction that males unable to monopolize reproduction are also unable to maintain their dominant status over time. We examine whether the probability of losing dominance is correlated positively with the occurrence of extra pair paternity (EPP) in the previous reproductive event. Finally, we attempt to identify the underlying mechanisms by investigating the link between the number of subordinates and the body mass of the dominant animals. We thus (3) test the prediction that the number of potential competitors influences dominants' body mass; and (4) examine whether the dominant male body mass influences its probability of losing dominance.Both the probability of maintaining dominance  and the The likelihood that the dominant male would lose its dominance is multiplied by 2.16 [CI95%: 1.23–3.79] when an EPP occurred at the previous reproductive event  declines . A male with a large number of male subordinates is in lower body condition and may consequently be more likely to lose paternity and then dominance.How do social factors affect the ability of dominant males to monopolize reproduction and secure dominance? One explanation is that it is simply impossible for dominant males to control each of numerous subordinates with fighting abilities We suggest that the general process by which the number of subordinates imposes costs on the dominants is that controlling many subordinate males leads to an energetic cost for these males, and this leads to losing body reserves. This mass loss may in turn lower their capacity to guard their mate effectively, thus allowing other males to gain extra-pair paternity and lowering the dominant male's ability to win contests for dominance. The cost generated by the presence of competitors in social groups may counterbalance the benefits provided by social living Préfecture de la Savoie. Sophie Lardy is authorized for experimentation with animals, issued by the French Ministry of Agriculture and Fisheries (diploma n/0ETRY20090520). French law does not demand approval by an ethical committee.The field work conducted in the Alpine marmots was undertaken after acceptance of the project by the scientific committee of the Vanoise National Park, and after the deliverance of the permit number AP n 2010/121 by the Alpine marmots are cooperatively breeding rodents which live in family groups where only the dominant pair reproduces, as a rule. Both males and females may stay as dominants on the same territory for several years , until they die or get evicted by a competitor. Eviction is generally followed by death, for dominants of both sexes Taraxacum densleonis). Once captured, the animals were tranquilized with Zolétil 100  were used thereafter. An additional correction for body size  did not change the results, so we present only the results with RBM. The influence of RBM on the probability of losing dominance was investigated first. Generalized mixed models (GLMM) with male identity within territory as random factors, a logit link function and a binomial error distribution were used to account for repeated measures and for the binomial distribution of the dependent variable. To verify that the effect of the number of subordinates on male RBM was not an effect of resource limitation due to high densities of individuals in the territories, the effect of the number of subordinates on dominant female RBM was also studied with the same procedure as the one used for males. The RBM of males staying dominant was then compared to the RBM of males losing dominance using linear mixed models with male identity within territory as random factors to account for repeated measures. Finally we compared the RBM of a male (Statistical analyses were performed with R 2.10.1


The organization of networks of interacting species, such as plants and animals engaged in mutualisms, strongly influences the ecology and evolution of partner communities. Habitat fragmentation is a globally pervasive form of spatial heterogeneity that could profoundly impact the structure of mutualist networks. This is particularly true for biodiversity-rich tropical ecosystems, where the majority of plant species depend on mutualisms with animals and it is thought that changes in the structure of mutualist networks could lead to cascades of extinctions.We evaluated effects of fragmentation on mutualistic networks by calculating metrics of network structure for ant-plant networks in continuous Amazonian forests with those in forest fragments. We hypothesized that networks in fragments would have fewer species and higher connectance, but equal nestedness and resilience compared to forest networks. Only one of the nine metrics we compared differed between continuous forest and forest fragments, indicating that networks were resistant to the biotic and abiotic changes that accompany fragmentation. This is partially the result of the loss of only specialist species with one connection that were lost in forest fragments.We found that the networks of ant-plant mutualists in twenty-five year old fragments are similar to those in continuous forest, suggesting these interactions are resistant to the detrimental changes associated with habitat fragmentation, at least in landscapes that are a mosaic of fragments, regenerating forests, and pastures. However, ant-plant mutualistic networks may have several properties that may promote their persistence in fragmented landscapes. Proactive identification of key mutualist partners may be necessary to focus conservation efforts on the interactions that insure the integrity of network structure and the ecosystems services networks provide. While there is much to be learned about the dynamics of mutualisms from the study of pair-wise interactions et al.et al.Despite these advances, however, most studies of mutualist networks fail to consider the complexity of the landscape in which these communities are embedded Mutualisms between ants and specialized plants known as myrmecophytes are a defining feature of tropical forests We evaluated the effect of habitat fragmentation on the structure of mutualistic networks using the community of ant-plant partners found in an experimentally fragmented landscape in the central Amazon. By comparing these networks in continuous forest sites with those in forest fragments, we provide the first empirical test of the effects of habitat fragmentation on network structure that have been put forward in prior theoretical and empirical work. To do so, we begin by comparing the diversity of ants and plants in fragments and continuous forest. Because species diversity of both plants and animals decreases in tropical forest fragments All necessary permits were obtained for the described field studies. All research was conducted with the approval of Brazil's National Council of Scientific and Technological Development  and the Brazilian Institute of Environment and Renewable Natural Resources .et al.We conducted our study in the lowland tropical forests of Brazil's Biological Dynamics of Forest Fragments Project . From October 2001 to February 2002, we conducted surveys of the comprehensively described ant-plant mutualist community Azteca species as a single taxon because of unresolved taxonomy of this group. We also pooled all Pouruma (Cecropiaceae) into a single taxon because of the difficulty in classifying individuals to species with floral characters and no individuals were fertile during our surveys. Finally, difficulty in distinguishing among juvenile Tachigali trees led us to exclude smaller individuals found in two CF plots  and two FF plots , although all adult trees were readily identified.In each of our eight study sites we established a 100 m×100 m plot in which we mapped all ant-plants and recorded the presence and identity of ant colonies in their domatia; vouchers of plants and ants were collected to confirm identifications. Here we analyze the network connections between the 12 myrmecophytes we recorded in our surveys and the 10 obligate ant species associated with them reported in Hypotheses about network structure can be addressed using both qualitative and quantitative approaches. Qualitative metrics are calculated from binary interaction matrices while quantitative metrics include information on the frequency of individual interactions. Qualitative metrics are still commonly used to study networks, and hence they are useful for comparing the results of our work with those of other studies. However, the frequency of an interaction between species is an important measure of its strength and hence importance To determine if ant and plant species richness was lower in fragments (Hypothesis 1), we compared the number of ant and plant species in the networks. We then tested whether there were fewer realized interactions between ants and plants in fragments  by comparing the number of links per species, network connectance , and linkage density (quantitative) for each treatment with separate one-way ANOVAs. Because there is the potential for correlation among different metrics of network structure et al.Finally, to test if networks in fragments and continuous forest were equally resilient to disturbance (Hypothesis 4) we calculated the network robustness (R) to simulated extinction of ant or plant species . The quaWe censused N = 322 myrmecophytic plants in forest fragments and N = 653 in continuous forest; for a detailed description of these results see We found that networks in continuous forest had significantly more plant species than networks in forest fragments  were associated with only one ant species in continuous forest sites. Such associations formed isolated subwebs, which are common in symbiotic interaction networks It is also important to emphasize that ant-plant mutualistic networks have several unique properties that may promote their persistence in fragmented landscapes. Nested mutualistic networks are expected to be resilient to species losses if extinctions involve specialists that are involved in fewer interactions within the network In general, it appears that the resilience of mutualistic networks is enhanced by higher species richness, network connectivity, and through strong, symmetric interaction within highly nested networks Although our study was not designed to compare within-habitat variation in the structure of networks, it appears that replicates within a single habitat class were often quite variable. Within habitat heterogeneity is hypothesized to have a major influence on network topology Azteca remains challenging and has yet to be fully resolved for our study sites Azteca species in a single taxon for our analyses. Our ongoing molecular analyses are attempting to determine the number of Azteca species colonizing myrmecophytes, and including multiple Azteca species species will clearly alter the structure of networks. However, the overall conclusion that networks are similar in forest fragments and continuous forests will likely remain unchanged – with the exception of Cordia nodosa, plant species colonized by Azteca are relatively rare Three important caveats to our results bear consideration. First, the taxonomies of the ant genus Allomerus octoarticulatus and Hirtella myrmecophila in our network), it may be possible to focus conservation efforts on those species in addition to the more commonly targeted rare or endemic ones as a means of ensuring the integrity of network structure and ecosystem services these networks provide We conclude that the redundancy built into mutualistic networks and the limited number of 1∶1 interactions in tropical ant-plant systems makes these networks inherently resistant to the effects of fragmentation, at least in the short term Table S1Tables for one-way ANOVAs of nine network metrics. The metric with a significant p-value  is in bold.(DOC)Click here for additional data file.


PLoS Computational Biology we have tried to support this evolution through a collection of educational articles pertinent to the undergraduate level and beyond. It is only natural that we would take the next step Bioinformatics is now an integral part of biology and biological research. The field began with a few people from other disciplines teaching themselves and each other the techniques that are now considered commonplace. These pioneers then began graduate programs We now introduce a subsection of the Education section with articles devoted to teaching bioinformatics in secondary schools that is derived from the work of the Education committee of the International Society for Computational Biology (ISCB), who identified a need to address the issue of incorporating bioinformatics into secondary school biology classes. They also recognized the interest among researchers to build and participate in outreach programs at the secondary school level given that many funding agencies worldwide encourage such a component in grant applications.To move the ball forward on secondary school bioinformatics education, at ISCB's 2010 international conference, Intelligent Systems in Molecular Biology (ISMB), the ISCB Education committee organized a half-day tutorial aimed at secondary school biology and chemistry teachers in the Boston area interested in learning about bioinformatics and how to include it in their curricula. The tutorial also attracted researchers involved in organizing or formulating outreach programs in their community. The main focus of the ISMB tutorial was the presentation of lesson plans by a secondary school teacher  who has successfully incorporated bioinformatics into his courses for more than five years. His is one example of such an effort and is embraced in the Ten Simple Rules and its supplementary material found in this issue. Also in this issue we have an article by Suzanne Gallagher and colleagues on the experience of teaching secondary school level bioinformatics in Boulder, Colorado.There are many examples of outreach efforts to high school students that we would like to feature in coming months, which incorporate bioinformatics into their programs see .Briefings in Bioinformatics was dedicated to bioinformatics education There are many other examples of educators doing similar work in school districts worldwide. A recent issue of We encourage feedback of any form, including comments on this editorial, and hearing about your experience teaching bioinformatics to secondary school students.


There is a significant body of research indicating having a genetic condition is emotionally burdensome for the individual and their family. One goal of cancer genetic counselling is to assist patients to adapt to the news that they and family members are at significantly increased risk of developing cancer. Numerous studies have shown that the majority of patients who attend cancer genetic services do not report significantly increased long-term psychological distress. However, a small number of patients present with pre-existing complex psychological issues or particular personality traits which are not readily apparent. This subgroup of individuals may experience adverse psychological responses and complex adjustment challenges following their participation in the genetic counselling process.


Optimizing Delivery of Health care Interventions (ODHIN) is an ongoing European project  involving research institutions from 9 European countries using the implementation of Early Identification and Brief Intervention (EIBI) programmes for Hazardous and Harmful Alcohol Consumption (HHAC) in Primary Health Care (PHC) as a case study to better understand how to translate the results of clinical research into everyday practice. The Italian National Health Service (ISS) is the project leader of the Work Package 6 assessment tool. The aim of the ODHIN assessment tool is to formalise, operationalise and test the questionnaire developed under the PHEPA project in order to produce an update instrument to assess the extent of implementation of EIBIs for HHAC throughout PHC settings. The ODHIN assessment tool has been conceived as a semi-structured questionnaire for the identification of the state of the art, gaps and areas in the country that need further work and strengthening; to monitor the adequacy of brief intervention programmes for HHAC in order to provide recommendations to improve and optimize delivery of health care interventions. It analyses 24 questions distributed across 7 key sections. Data have been collected from 9 ODHIN collaborating countries  and from other 14 European countries who have agreed to share their national experience with the ODHIN partners . Preliminary data on the state of the art of the implementation and the extent of EIBI for HHAC throughout PHC settings across 23 European participating countries will be presented. Identified areas where services require development or strengthening across the participating countries as well as examples of good practices between countries will be also discussed.


PLoS Medicine editors discuss new research studies on the risks associated with mode of childbirth following caesarean section.The  PLoS Medicine publishes two research articles with new data that should help women and clinicians make better informed decisions about childbirth This month, planned, as opposed to actual, birth mode, which therefore helps clinicians to counsel women on the outcomes associated with their choice.One study The second study this birth, but for subsequent births too. For example, as highlighted by Crowther and colleagues The bigger issue raised by these findings relates to how clinicians and women can work together to make the best possible decision when so many questions remain unanswered. The existing research presents an incomplete picture of the entire set of possible risks associated with the options that women and clinicians have; under-studied issues relate to the implications not just for


Identification of prognostic and predictive biomarkers is important for targeting treatments to patients and for the design and analysis of randomised controlled trials. Cox proportional hazards modelling is a standard method for assessing prognostic value of clinical biomarkers where time to occurrence of an event is the primary outcome of interest. An important issue in the analysis of prognostic factors is the functional form of the relationship between the factor and outcome specifically for continuous covariates. Continuous covariates are often simplified assuming a linear relationship with log-hazard or dichotomisation which may be inappropriate leading to loss of efficiency in statistical tests, bias and incorrect conclusions. The effects of important prognostic biomarkers may go unrecognised due to simplistic assumptions made in statistical modelling.Two polynomial based strategies, restricted cubic splines and fractional polynomials, are compared directly for determining the functional form of non-linear relationships between prognostic biomarkers and survival using two real datasets from randomised controlled trials in advanced pancreatic cancer and cardiac surgery. Fractional polynomials are an extended family of curves including non-integer and negative power terms. Spline functions are piecewise polynomials connected across intervals of a variable constrained to meet at the ‘knots’.Multivariable models were constructed based on Cox proportional hazards regression using backward elimination. Internal validation to directly compare the fit of the restricted cubic spline and fractional polynomial strategies was carried out by calculating the sampling distribution of the difference in AIC between the models using nonparametric bootstrap analyses. Further analysis recalculated the univariate fractional polynomial transformation within each bootstrap resample to compare directly against a 5-knot restricted cubic spline. The influence of the size of the bootstrap samples was also investigated.The fitted functions generated by splines and fractional polynomials were similar resulting in comparable models. The methods are generally different in the extremities where there is often a paucity of data. Larger differences were seen between the two methods when sample sizes were reduced due to the reduced power to detect small effects but also to detect nonlinearity.Multivariable fractional polynomial transformations are an alternative approach to restricted cubic spline transformations for multivariable model building of continuous biomarkers with non-linear relationships with outcome.