Patient and public involvement (PPI), inclusion of members of the public as active partners in the research process, can be a requirement of research funding. Limited evidence has suggested that clinical trials may be particularly likely to benefit from PPI. There is a lack of critical assessment of PPI and suggestions in the literature of selective reporting of its benefits. This study aims to increase the knowledge of PPI in clinical trials by systematically investigating how it is approached within a cohort of public funded randomised trials in the UK.Documentation from the application process for all randomised trials funded by the National Institute for Health Research Health Technology Assessment (NIHR HTA) programme between 2006 and 2010 were obtained. Data relating to PPI activity and how these plans were assessed within the peer review process were extracted.Documentation to allow details of planned PPI activity to be extracted were available in 107 RCTs. PPI representation was not described in 15% with representation on TSCs, DMCs, and TMGs described in 53%, 8%, and 12% of applications respectively. A consultancy approach was described in 26%.Of the 515 reviewers comments across the trials only 211(41%) commented on PPI plans. The majority repeated the PPI plans from the application rather than commenting on their suitability.Research applicants frequently describe PPI but reviewers seem unable to comment on suitability of the approach. Evidence of impact is needed to inform future approaches for applicants and peer reviewers.


What mechanisms underlie this impact of emotion on perception? Evidence suggests that emotion-induced blindness may be distinguishable from closely related phenomena such as the orienting of spatial attention to emotional stimuli or the central resource bottlenecks commonly associated with the attentional blink. Instead, we suggest that emotion-induced blindness reflects relatively early competition between targets and emotional distractors, where spontaneous prioritization of emotional stimuli leads to suppression of competing perceptual representations potentially linked to an overlapping point in time and space.Emotional visual scenes are such powerful attractors of attention that they can disrupt perception of other stimuli that appear soon afterward, an effect known as  Most aspects of the environment resonate with emotional meaning, so an understanding of perception in the real world necessitates understanding how it is impacted by emotion. Evidence suggests that emotional stimuli themselves attract attention more robustly and are more readily detected than are non-emotional stimuli  of upright landscape and architecture photos at a rate of 10 images per second. They were instructed to search within each stream for a landscape or architecture photo that was rotated 90° clockwise or counterclockwise and to report its orientation  was equally likely to appear in the same stream as the target or in the opposite stream. Results revealed that target perception was worse following an emotional distractor only when the critical distractor appeared in the same stream as the target . At the end of the experiment, the female participants were asked to rate their level of unease about the fact that their partner had been rating other women; in two separate experiments, there was a robust correlation between self-rated unease and emotion-induced blindness  perception of neighboring targets through relatively central, late-stage mechanisms as well . The evidence reviewed in the present discussion highlights potential spatiotemporal competition mechanisms; further characterization of the loci at which emotion can impact visual processing holds promise for more fully understanding the myriad ways that it can shape our conscious perception of the world.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.


Urachal remnant disease is uncommon in adults and can present with symptoms ranging from drainage near the umbilicus to a severe abdominal infection. Most cases are referred for treatment once diagnosed either clinically or radiographically with ultrasound or computerized tomography. We present a unique case of an infected urachal cyst visualized on a series of CT scans in an adult patient with abdominal pain over a period of years. A 33-year-old-male patient presented initially with lower abdominal pain in March 2006. He was diagnosed with appendicitis based upon his exam and history. A CT scan of the abdomen was performed at that time and demonstrated extensive inflammatory changes in the right lower quadrant with possible interloop abscess . Two nonThe patient presented again in August 2011 with right flank pain and urinary symptoms. A noncontrast CT scan of the abdomen was performed and demonstrated a right ureterovesicular junction calculus with mild right ureteral dilation . Again, He subsequently presented again 3 weeks later with severe abdominal pain and induration of his lower abdominal wall. CT imaging now demonstrated interval enlargement of a complex cystic mass inseparable from the anterior superior wall of the urinary balder and abutting the posterior margin of the abdominal wall . The radAt the time of surgery, cystoscopy did not demonstrate any abnormalities of the bladder. Exploratory laparotomy was performed and an indurated mass and abscess were encountered near the area of the anterior abdominal wall and bladder. The abscess was drained and a few small calcifications were encountered and removed for pathologic examination. A complete exploration was performed and the phlegmon appeared to be limited to the dome of the bladder. This area was excised and the dome of the bladder was closed primarily in layers with absorbable suture. Drains were placed and the abdominal wall was debrided and closed. He had an uncomplicated postoperative course. Final pathology demonstrated urachal remnants with no evidence of malignancy. The urachus is an embryologic tract that extends from the bladder to the umbilicus during development . RemnantOur case highlights the potential complications related to an urachal cyst disease in one patient who was treated for multiple causes of lower abdominal pain. The initial presentation of appendicitis was the first glimpse of the cystic remnant disease. The lower abdominal inflammatory changes were nonspecific and therefore it was impossible to differentiate perforated appendicitis with a fecalith from a less common cause of infection. Since the operative and pathologic findings were consistent with appendicitis at that time, consideration of a simultaneous condition was not considered.Later when the patient presented with a ureterovesicular stone and mild hydronephrosis, the CT scan demonstrated the proximity of the lower abdominal calcifications to the bladder. However, at that time there was no obvious inflammatory changes or infection associated with the bladder or abdominal wall and his symptoms were more consistent with nephroureter obstruction. Despite the radiographic presence of the urachal cyst each time the patient was evaluated for his symptoms, he was diagnosed with a potentially more common cause of pain each time. It was not until the patient developed a severe infection of his lower abdominal wall that the urachal cyst was finally treated surgically and excised. Urachal remnant disease should be considered in any patient with calcifications or cysts adjacent to the anterior abdominal wall or bladder dome. Urachal disease can be an incidental finding radiographically or it may present once infection or some other complication develops. Our case presentation highlights the potential for early diagnosis or potential misdiagnosis due to the frequent use of computerized tomography for patients with lower abdominal pain.


The positioning of the patient on the fracture table is critical to the successful reduction and operative fixation of hip fractures which are fixed using the dynamic hip screw system (DHS). There is a standard setup which is commonly used with relative ease. Yet the positioning of patients with amputations either above or below knee of the affected side can pose a significant challenge. We describe a novel positioning technique used on a 51-year old patient with a right above knee amputation who sustained an intertrochanteric extracapsular hip fracture. Hip fractures are a common source of morbidity and mortality worldwide . The incThis standard setup is quick and is achievable with relative ease in patients with intact lower limbs. The positioning of patients with amputations either above or below knee of the affected side can pose a significant challenge. We describe a positioning technique used on a 51-year old patient with a right above knee amputation who sustained an intertrochanteric extr-capsular hip fracture.A 51-year-old male with a right above knee amputation presented to the emergency department with a painful right hip subsequent to a fall on that side. He had been mobilising with two crutches for the previous four weeks while awaiting new prosthesis for the right above knee amputation from previous infected total knee arthroplasty.Plain film radiographs revealed an undisplaced extracapsular intertrochanteric fracture of the right hip .As an active and mobile amputee with a functional prosthesis, the patient was scheduled for a DHS fixation of the right intertrochanteric hip fracture with spinal anaesthesia. Securing the amputated limb poses a challenge in patients with above knee amputations. Our setup involved the standard fracture table used routinely to position a patient for DHS fixation. Adhesive fabric tape  was used to secure the stump to the distal end of the fracture table in a similar manner to the application of skin traction. Combining a specially formulated porous adhesive and a superior woven cloth, Elastoplast now Tensoplast, provided satisfactory adhesion while remaining secure in place. Such adhesive fabric tape and a crepe bandage was used circumferentially around the distal stump to further secure the limb .The DHS fixation was uncomplicated and the patient's recovery was uneventful. The patient was mobilised full weight bearing as tolerated with physiotherapy and discharged two days postoperatively. The post operative radiographs were satisfactory  and at tThere is little in the literature regarding the management of intertrochanteric hip fractures in patients with ipsilateral above or below knee amputations. Securing the amputated limb to the fracture table poses a significant challenge. Al-Harthy et al.  describeLimbs that have undergone an above knee amputation can have short stumps that can be very challenging to position or apply traction to. To our knowledge, there is only one report on the positioning technique for patients with a fracture and an above knee amputation. Aqil et al.  describeOur technique is an alternative to those described above. While the skin traction facilitated positioning of the limb, it provided little rotation control. Our patient had an undisplaced fracture and our technique resulted in a timely and satisfactory fixation. Due to the size of the stump and the small area the skin traction is applied to, it cannot generate any significant amount of traction prior to it getting unravelled. It may be conceivably more useful in below knee amputees where adequate skin traction and therefore traction may be applied. The skin around the stump needs to be carefully inspected prior to application of this technique as any fragile areas may become prone to breaking down during the procedure if prolonged.Some level of rotation can be applied using a wooden stick or a metal bar placed within the crepe bandage limbs and applying rotation towards the desired direction. Yet if significant traction and rotation control were needed for the reduction and fixation of these fractures, the use of skeletal pin traction may be necessary. The application of such a pin carries with it the risk of injury to the soft tissues of the stump. The pin may pull out of the osteoporotic bone on application of traction.There is little in the literature regarding the intraoperative positioning of patients with a hip fracture and an above knee amputation. There is one previous report and we describe an alternative technique for the positioning of a patient with an extracapsular hip fracture and an ipsilateral above knee amputation.


The objective of this study is to discuss some of the issues and give some examples of dealing with clustering in individually and cluster randomised trial sample size calculations.Clustering often occurs in individually randomised trials and is sometimes ignored when calculating sample sizes. Examples include practitioner effects in individually randomised trials with more than one practitioner or therapist effects from group interventions where clustering may be in one arm only. Additional levels of clustering may also occur in cluster randomised trials and estimating their effects can be difficult.Sample size calculations for several recent grant applications submitted by the South East Wales Trials Unit (SEWTU) have attempted to account for clustering or reduce inter-practitioner variation in different ways.Example 1: Clustering effects in an individually randomised trial of a group intervention for drug and alcohol detoxification based in prison were estimated for the intervention arm and the sample size of both arms inflated. Example 2: Clustering effects of anaesthetist were not estimated for a multi arm trial of 4 different airways devices but sample sizes were inflated to allow for small unknown effects. Sample size estimation used comparative and equivalence methods in three parallel multi arm trials. Example 3: Possible clustering in a trial of fissure sealant vs fluoride varnish at the school or family level was not accounted for in sample size calculations. All schools in the trial are Communities First schools and likely to be fairly homogeneous. Example 4: Unknown clustering effects of weight loss slimming groups were not accounted for in the intervention arm of a cluster randomised trials of a healthy lifestyle programme in obese pregnant women. Training has been implemented to reduce variability among group leaders.There appears to be no consensus regarding dealing with additional clustering effects and best efforts are made on a trial by trial basis for sample size estimation. Access to data for the estimation of intraclustering correlation coefficients and/or dissemination of the results will benefit all researchers designing trials with clustering issues.


Two major neurological disorders – Parkinson’s disease and dystonia – are believed to involve pathology in the activity of the basal ganglia, a subcortical brain structure, whose output nuclei  projects to thalamus and modulates thalamocortical relay. While these disorders may ultimately involve different network and cellular pathologies, some pathological physiology may be shared between them because surgical treatment of both conditions includes surgical lesion or electrical stimulation to GPi . This work compares the thalamocortical relay responses to inhibitory inputs from internal segment of GPi in Parkinson’s disease and in dystonia.Experimental data suggest that both conditions are marked by stronger oscillatory activity. In dystonia this activity becomes pathologically strong in the theta and alpha bands ,2, whileThe results of the study of the “hybrid” system  reveal a substantial similarity in the properties of relay in Parkinson’s disease and in dystonia. TC relay fidelity is substantially impaired due to the pathological pattern of GPi signals in both conditions. The results are robust with respect to variations of the model details and the types of incoming excitatory synaptic input.The results suggest that even though the rhythmicity in Parkinson’s disease and dystonia are confined to different frequency bands, their effect on the dynamics of downstream circuits is similar. Thus given the differences in dystonic and parkinsonian symptoms these results suggest the existence of mechanisms beyond pathological rhythmicity and thalamocortical relay in at least in one of the conditions. On the other hand, overlap in some motor deficits of dystonia and Parkinson’s disease may be attributed to the existence of similar pathological rhythmicities and the resulting deficiencies of thalamic relay.


The project focussed on two local services in Wales that have recently moved to  an integrated health and social care intellectual disabilities service.What are the advantages and disadvantages of service integration as viewed by parents with respect to care provision for young people with intellectual disabilities?We conducted a parental survey facilitated by nursing staff in both local services.Parents were generally skeptical of any positive impact of organisational changes on quality of care for children with LD. The main issues of concern for parents, however, did NOT relate to integration but to lack of resources and quality of care provision. This has serious implications for the way in which we should evaluate organisational changes such as health and social care integration for this user group.Parental concerns cover a wide range of issues. These issues reflect the unique needs of service users. Evaluating the impact of service integration for service users need to take account of different needs and abilities in this population group. The study also helps us to appreciate the limitations of parental surveys to measure service integration outcomes.


Associated neurospinal dysraphism in combination with anomalies of the genitourinary tract is well known in children with imperforate anus. There is a broad spectrum of concomittant anomalies with the OEIS Syndrome as the most serious endpoint. OEIS is an acronym for omphalocele, exstrophy , imperforate anus and spinal defects. At present almost all cases of OEIS are diagnosed prenatally and the patients should be treated at a specialized center with a multidisciplinary team. The complex diagnostic procedures and surgical measures are addressed as well as the difficulties in achieving continence in these patients.We present data of six patients with imperforate anus and spinal dysraphism  currently managed in the spina bifida clinic of the Children’s Hospital of Cologne. Two of them presenting the complete OEIS syndrome symptoms, another two with cloacal exstrophy without omphalocele and two with major renal malformations. Only two of six patients had hydrocephalus.The often difficult and multiple reconstructive surgical procedures in these patients are described . Especially the management of incontinence is extremely complex in these patients. For instance there is no sufficient bladder capacity in patients following initial closure of bladder exstrophy and there is only a weak or no function of the anal sphincter following pull-through procedures.OEIS syndrome is a devastating combination of anomalies resulting in a neurological deficit similar to myelomeningocele. In contrast to the functional problems arising in spina bifida patients, children with OEIS syndrome have functional impairment with additional problems due to the malformed urogenital tract and anorectal system. Management of children with OEIS syndrome demands a careful management plan starting already in the prenatal period and resulting in a life-long surveillance. Treatment of these patients should only be performed by a multidisciplinary team in a specialized center.


Although there is a substantial literature about the effectiveness of psychological therapies such as relaxation for pediatric chronic pain and about mindfulness meditation (MM) for health and mental health conditions, there has been little systematic attention to the use of MM for pediatric chronic pain. This presentation will address lessons learned from our ongoing clinical trial of MM in a pediatric chronic pain service at a university clinic.We present case material from our ongoing pilot clinical trial of a manualized mindfulness meditation intervention, called Inner Resources for Coping with Chronic Pain . Participants are 30 patients diagnosed with chronic pain and aged 11 – 17 receiving a 6-week, group-based meditation intervention that includes daily home practice of the techniques. Case material from two participants will be presented to illustrate effects and precautions.Our case material indicates that patients are able to learn and practice the MM techniques, with good adherence to the home practice. A male patient with multiple pain complaints was able to learn and practice the meditation techniques and use them to cope with stressors associated with his medical conditions. A 16 year old female patient with longstanding participation in pain management that primarily involved distraction found the concurrent use of mindfulness and distraction to be confusing and ineffective.MM shows promise as an intervention for helping children and adolescents to deal with chronic pain. The children and adolescents in our clinical trial have evidenced the ability to engage with the material and adhere to regular home practice of the techniques and application of them to presenting problems. However, a note of caution is raised by the possible incompatibility of mindfulness with concurrent therapies emphasizing the use of distraction for dealing with chronic pain.


Clark's article provides a useful synthesis of theoretical and empirical work evincing the brain as a prediction machine and proposing bi-directional, prediction error estimation as a fundamental mechanism of adaptive brain function. Accordingly, in Bayesian terminology both cognitive and perceptual mental states can be understood as statistical posterior distributions formed by integrating encountered data (with specific likelihoods) with prior beliefs (in turn with their own prior distributions). In his discussion of this unifying framework, Clark elegantly describes how updating priors with the aim of minimizing prediction error can sometimes result in illusory experience. When faced with stimuli manipulated to have multiple possible hidden causes, ambiguity is resolved by selecting the most likely explanation given prior beliefs about those hidden causes. As such, in conditions such as those created for the sound-induced visual illusion  and delusional beliefs ; with a marked impact on social and occupational functioning. The underlying mechanisms giving rise to these phenomena remain unclear, and current treatment is largely based on medication to block sub-cortical dopaminergic receptors, allied to cognitive behavioral psychological approaches to reduce distress associated with these symptoms. Examination of individuals with schizophrenia demonstrates that they are less susceptible to perceptual illusions than healthy individuals. For instance, the McGurk phenomenon by which incongruence between certain lip movements and speech sounds produces the perception of alternative speech sounds appears to be exhibited to a lesser degree in individuals with schizophrenia (Pearl et al., Can the findings of reduced susceptibility to perceptual illusions be viewed as conferring a schizophrenia-related behavioral advantage? If so, is this outperformance of healthy individuals by those with schizophrenia best explained by a predictive failure? The findings of our own laboratory provide empirical evidence that predictive abnormalities are not restricted to passive sensation – in accord with Clark's suggestion of prediction as a universal neural mechanism – but extend to predictions made on the basis of self-generated movement. Individuals with schizophrenia differ from healthy individuals in their ability to estimate the level of force necessary to match a force applied directly to themselves (Shergill et al., Computational modeling has proven valuable in the characterization of behavioral and neurophysiological parameters relating to the updating of Bayesian processes during information processing in schizophrenia (for example, Averbeck et al., The study of wide-ranging illusions presents a potentially fertile means of understanding the intricacies of predictive failures in schizophrenia as each illusion draws on specific perceptual and cognitive priors. On the flip side, the study of illusion potentially provides a tantalizing model for the study of distorted reality in the healthy brain. Furthermore, given the efficacy of dopaminergic pharmacological neuromodulation in patients with schizophrenia, there is an urgent need for examination of the role of neurotransmitters in mediating predictive coding.


Postgraduate training is a dynamic activity. Over the years it is undergoing increasing standardization. In the past programs have been haphazard and inconsistent but now structured curriculum are in place. Comprehensive details related to criteria of entry, duration of training, core knowledge areas, and competencies required can be found. How program is to be run is explicitly chalked down and log books developed to be completed by trainees. In Pakistan one such model is implemented by College of Physicians and Surgeons Pakistan (CPSP). The program was developed through a well organized activity with explicit guidelines, under supervision of medical educationists, who initially trained program directors through various educational workshops. Few medical universities have also developed curriculum related to pediatric surgery but how they are developed is not known. While CPSP training program is uniform throughout the country, university program varies. There is also a comprehensive evaluation system with CPSP program and evaluation strategies are accessible to both trainees and trainers and evaluators.The magic figure of three years of residency in pediatric surgery  in CPSP model is questioned by few program directors. In United States the total duration of training in pediatric surgery after general surgery residency, is two years. The 18 months training comprise of clinical pediatric surgery and the remaining six months may be spent in related clinical disciplines to enhance the educational experience, or get involved in scholarly activities. It raises question as to how general surgery residency in US model is beneficial to those seeking career in pediatric surgery. In this model the pediatric surgery resident spends only 25% of his total training in core curriculum of his own discipline. During this time period it is expected that trainee must document a total of 800 major pediatric surgery procedures as surgeon and the service providing training must cater for at least 1200 core surgical procedures per year. It is for pediatric surgeons to ponder for unique requirements for patient population and trainees [The magic figure of three years of residency in pediatric surgery  in CPSP model is questioned by few program directors. In United States the total duration of training in pediatric surgery after general surgery residency, is two years. The 18 months training comprise of clinical pediatric surgery and the remaining six months may be spent in related clinical disciplines to enhance the educational experience, or get involved in scholarly activities. It raises question as to how general surgery residency in US model is beneficial to those seeking career in pediatric surgery. In this model the pediatric surgery resident spends only 25% of his total training in core curriculum of his own discipline. During this time period it is expected that trainee must document a total of 800 major pediatric surgery procedures as surgeon and the service providing training must cater for at least 1200 core surgical procedures per year. It is for pediatric surgeons to ponder for unique requirements for patient population and trainees [Accreditation of the services for training in pediatric surgery is another painstaking assignment. An elaborate form has been developed by CPSP to be filled in by the program directors providing details of workload, facilities offered, number and expertise of teaching faculty etc. It is an observation that departments of pediatric surgery in the country are heterogeneous thus training imparted may not be uniform. Some services may get recognition even when facilities like ICU care, minimally invasive surgery etc are not optimal. Thus need of rotation to other centers where such exposure is guaranteed, must be looked into.The two important areas not addressed with CPSP model are, compliance with the residency program, periodic evaluation and need of changes that may be required in this era of rapid technological advancement with new evidence based data related to diseases. No study has been conducted by pediatric surgeons in this regard to objectively address the issue. The Association of Paediatric Surgeons of Pakistan may gather a multi-institutional data to get some inference and suggest changes, if deemed necessary.Another important issue is evaluation of trainees. In United States continuous periodic assessment is made and feedback given while in contemporary evaluation system with CPSP only end exam is the deciding point though residents do complete log books of their training and write dissertation or a scientific paper but these are not counted in the final examination. The training institutes thus play a passive role and may feel isolated. The input from supervisors must be acknowledged at some level for which integrity of trainers themselves is an issue. The role of trainers in residency program must be assessed periodically by respective institutes and monitoring body. In addition residents should be asked to write an annual confidential report of their supervisors. This two way accountability and evaluation helps in raising the standard of training program and evaluation of both trainees and trainers.A residency program in pediatric surgery intends to impart advance knowledge coupled with hands on training to aspiring young doctors caring for children. An optimal program thus aims at producing safe surgeons, competent enough to take care of pediatric surgical patients referred to them.Source of Support: NilConflict of Interest: None declared


The atomistic modeling of protein adsorption on surfaces is hampered by the different time scales of the simulation ( The interaction of proteins with different biomaterials plays a vital role in describing their biocompatibility. Depending on the surface the overall protein structure may vary from native to unfolded A major problem that arises when using MD to study protein adsorption is the limited time scale of only a few hundred ns. The experimental time scale when these processes are investigated usually ranges from Based on the work by Voter In the present work, a comparison between classical and accelerated MD is used to show differences in the sampling of conformational changes during adsorption on a hydrophobic graphite surface. To our knowledge, it is the first time that the technique of aMD is used to study protein adsorption. We note that interest in adhesion studies focuses on the final structure and adhesion forces of the adsorbed molecule, since this is where comparison to experiment is possible. The actual adsorption dynamics are not so relevant; this feature makes adsorption a good candidate for aMD.Our protein of interest is the bone growth factor BMP-2 (bone morphogenetic protein 2) which is used to improve osteointegration by functionalizing implant surfaces All the simulations were carried out using NAMD 2.8 ayer see .For all simulations periodic boundary conditions are used with Particle Mesh Ewald (PME) After energy minimization all systems were equilibrated for 100 ps at a temperature of 310 K and constant pressure of 1 atm with the protein backbone atoms restrained in order to prevent adsorption before equilibration. Following the equilibration classical and accelerated MD simulations were carried out for 20 ns with a time step of 2.0 fs enabled by the SHAKE In order to sufficiently sample the conformational space of adsorption the implementation of accelerated molecular dynamics (aMD) We also let these simulations run for The mass weighted radius of gyration is defined as:Furthermore, principal-component analysis using the cartesian coordinates of the protein atoms was performed with the GROMACS The adsorption snapshots were rendered using VMD During the first 100 ps both classical and accelerated simulations show a similar trend. The protein approaches the graphite surface driven by attractive van-der-Waals interactions. But very soon classical and accelerated simulations show quite a different adsorption behavior. In the case of aMD, conformational transitions start to occur instantly whereas cMD simulations show very little structural rearrangements after the protein got in contact with the surface. During the accelerated simulations not only the protein motions but also the solvent motions were affected. Since dehydration of the surface is an essential but time consuming step in the adsorption process The final adsorption snapshots after 20 ns, which compare cMD and aMD simulations , clearlyThe protein, in the case of aMD, has spread completely on the graphite surface and forms a flat peptide monolayer. This can be confirmed by the temporal evolution of the radius of gyration . Here, oteps see ; this feInterestingly, both orientations in the case of aMD show the same secondary structure content after adsorption as can be seen in When comparing aMD and cMD one can clearly recognize that the helical and Additionally, we performed cartesian principal component analysis to identify the conformational space during protein adsorption . In thisComparing our results obtained by classical and accelerated molecular dynamics simulations we conclude that sufficient sampling of the conformational space is key to understanding protein adsorption. Since adsorption phenomena take place in time scales extending from The advantages of this method are – among many others see  – (i) thThe easiness of use and computational efficiency make aMD an ideal candidate for studying adsorption processes in large systems. Other interesting sampling techniques such as conformational flooding Our results suggest that the monomeric form of BMP-2 does indeed unfold on a hydrophobic graphite surface as suggested by previous results Even though the dynamics of the adsorption process have been altered, the final adsorption state is most relevant in adsorption studies, since it can be compared with experimental results. From what we know from experimental results


Simultaneous oscillation of neuron groups could provide solution to the binding problem  and simuIn our experiments the Brian simulator  featurinThere might be some number of basic mechanisms that are responsible for processing and forwarding information in the brain, including a variety of synchronizing mechanisms. In this experiment we have shown how synchronized oscillations of neurons and decision making processes can be used for binding and forwarding information between the neuron groups.


Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. The recent interest in personalized medicine has highlighted the importance of genetic variability in the pathophysiology and outcome of human disease  or Type B (Unpredictable) Table  Rieder,. While TThe importance of enhancing drug safety in children is even more telling given the drug approval process Rieder, . The usuHistorically there have been five recognized risk factors for adverse drug reactions, of which several—extremes of age and impairment of the organs of clearance—apply to children; more recently, an additional two risk factors have been added, one of which—certain genetic polymorphisms—is a direct indication of the importance of pharmacogenomics in drug safety Table  Rieder,. Given tCancer is one of the commonest causes of death for children in developed countries, but also has been one of the major—and often unsung—success stories of pediatric pharmacotherapy. Over the past five decades, there has been remarkable overall success in terms of improved survival among children with cancer  is a key enzyme in the biotransformation of 6-mercaptopurine Figure  Pacific. 6-mercaThe fact that this observation was made three decades ago raises the question of why TPMT genotyping has not been a part of routine care for children with cancer for longer than it has  gene  and in the catechol-O-methyltransferase (COMT) gene (rs9332377) with severe cisplatin induced ototoxicity , poor metabolizer (PMs) and ultrarapid metabolizers (UMs) as the result of extensive polymorphisms for the gene encoding CYP2D6 . Thus, developing strategies to evaluate risk at the onset of therapy would be of obvious utility and as well would provide important insights into the pathophysiology of these adverse events, which remains unclear (Rieder, One of the most feared patterns of adverse drug reactions among children is drug hypersensitivity such as Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (Elzagallaai et al.,  Rieder, .*5701 has reduced the risk of serious skin rash from 3% to zero (Phillips et al., Initial pharmacogenomic studies in drug hypersensitivity have been somewhat disappointing Rieder, . Over thThe examples cited above should not be taken to mean they are the only care areas in which pharmacogenomics for children has the potential to improve drug safety. There are a number of other drugs commonly used in children for whom pharmacogenomic studies offer great potential in improving safety and efficacy (Downing et al., There is perhaps no area in which there is greater need for better defining therapy than pediatric psychopharmacology Arango, . While tWhen considering these studies there are serious questions that need to be asked, such as which should be priority drug targets for study? This issue has been given careful thought by a number of investigators and algorithms have been developed to identify targets for further study (Shaw et al., The use of pharmacogenomic information to inform diagnosis and guide therapy for children provides a series of interesting and unique ethical challenges. Implicit in therapy for children is the ethical conflict that the person giving consent—a parent or guardian—is not the one receiving the therapy. As an example, research conducting in the setting of childhood cancer demonstrated that when facing difficult therapeutic choices parents have difficulty in distinguishing their understanding of the situation from their child's experiences (Levi et al., A major additional challenge germane to pharmacogenomics is the concern that secondary information obtained during genetic testing may have a distant impact on access to insurance, employment or care (Netzer and Biller-Andorno, Our group has worked with parent groups in studying the ethical acceptability of genetic testing for their children and have found that their most important concerns were securing proper informed consent including ensuring that they had enough information to make a well informed decision. An additional concern was that their health care providers had the background and training to make appropriate decisions based on the results of genetic testing. This speaks strongly to the importance of patient and parent empowerment as well as to the need for including considerations on how to use genetic information for diagnosis and therapy in undergraduate and postgraduate health care professional training.One of the major directions that medical education and care has made over the past several decades has been in the development of evidence-based medicine and in clinical guidelines informed by evidence to enhance and optimize patient care. Our group and others are working to incorporate the use of genetic information into guidelines on the diagnosis and therapy of common and important conditions. One area in which this is most likely to take fruit in the short term is the area of pediatric oncology, where guidelines are being written to incorporate the results of pharmacogenomic analysis into the initial assessment, monitoring, and therapy of children with cancer. Cancer and chronic disease offer the potential for pharmacogenomic analysis as therapy is being planned, which provides the opportunity given real-time turn-around of genetic testing to be able to better define which children are at special risk for adverse drug events and to better plan how therapy might be more closely monitored or modified in these children.The potential of pharmacogenomics in improving therapy for children also applies in the development of new therapeutic agents, for which the potential for genetic variation impacting on efficacy and/or safety should be part of the research considerations and clinical trial design. Historically therapy for children has lagged behind therapy for adults—it is important that this should not be the case in the era of personalized medicine.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The firing rates of neurons in primate motor cortex have been related to multiple parameters of voluntary movement. This finding has been corroborated by stimulation-based studies that have mapped complex movements in rodent and primate motor cortex. However, it has been difficult to link the movement tuning of a neuron with its role within the cortical microcircuit. In sensory cortex, neuronal tuning is largely established by afferents delivering information from tuned receptors in the periphery. Motor cortex, which lacks the granular input layer, may be better understood by analyzing its efferent projections. As a primary source of cortical output, layer 5 neurons represent an ideal starting point for this line of experimentation. It is in these deep output layers that movements can most effectively be evoked by intracortical microstimulation and recordings can obtain the most useful signals for the control of motor prostheses. Studies focused on layer 5 output neurons have revealed that projection identity is a fundamental property related to the laminar position, receptive field and ion channel complement of these cells. Given the variety of brain areas targeted by layer 5 output neurons, knowledge of a neuron's downstream connectivity may provide insight into its movement tuning. Future experiments that relate motor behavior to the activity of neurons with a known projection identity will yield a more detailed understanding of the function of cortical microcircuits. One of the great achievements in neuroscience is our detailed understanding of the circuitry and function of the visual system. A well-defined anatomical framework and an established parameter space for visual stimulation have expedited research on the computations performed by the visual cortex. A particularly productive approach has been to develop circuit models of the visual cortex based on its multiple input channels and to associate these microcircuits with the macroscopic functional areas of visual cortex  type corticostriatal axons synapse in the ipsilateral striatum before continuing on toward the spinal cord. This differentiates them from intratelencephalic (IT) type corticostriatal neurons which cross the midline to project to the striatum and contralateral cortex but do not leave the telencephalon. IT and PT type neurons preferentially innervate direct and indirect pathway neurons of the striatum, respectively (Reiner et al., Neurons forming the corticospinal tract are predisposed to possessing movement tuning, but other descending pathways such as the rubrospinal tract are also heavily involved in motor control Lemon, . Nor is Movement tuning is a well-documented yet controversial property of motor cortex that has been successfully exploited for direct cortical control of neural prostheses (Hochberg et al., 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.


This review is focused on discussing in some detail possible neuroprotective functions of microglial cells. We strive to explain how loss of these essential microglial functions might contribute toward the development of characteristic neuropathological features that characterize Alzheimer’s disease. The conceptual framework guiding our thinking is provided by the hypothesis that microglial senescence accounts for impaired neuronal protection and consequent neurodegeneration. The role of CNS microglial cells in the development of Alzheimer’s disease(AD) has been the subject of considerable interest since McGeer’s initial description of reactive microglia in human AD brain in 1987 , and that it represents an immunologically subdued environment  or ferrous (Fe+2) ions. We propose that the sequestration of free iron in the CNS by ferritin in microglia constitutes an important neuroprotective mechanism that becomes most relevant when there is a breach in the BBB and the possibility exists of free iron entering the brain parenchyma. The evidence for this mechanism of microglial neuroprotection is as follows: we and others have previously reported that many of the dystrophic (senescent) microglia in human brain are positive for the iron storage protein, ferritin  A final aspect of microglial neuroprotection within the scope of this discussion concerns their emerging role in the regulation of the plasticity of neuronal circuits, that is, their involvement in the pruning/elimination and maintenance of synaptic connections. This aspect of the microglial functional repertoire was recognized for the first time more than 40 years ago by Blinzinger and Kreutzberg , yet it via mitosis of resident cells undergo programmed cell death which reduces cell numbers back to baseline  and certainly to studies in human brain which reveal a lack of Aβ phagocytosis by microglia. Thus, the relationship between Aβ, microglial activation, and/or neuroinflammation remains enigmatic and perplexing even after more than 20 years of intense research. If one also considers the alleged causal connection between amyloid deposits and neurofibrillary degeneration the picture gets blurred even more as this connection seems to grow weaker and evidence is mounting against rather than in favor of it.Countless studies in laboratory animals involving experimental CNS lesions have shown that microglia become activated rapidly in response to neuronal injury (Kreutzberg, Yet another issue that complicates our understanding of neuroinflammation in AD is found in the fact that primary infections outside of the CNS influence the state of microglial cells. In particular, sepsis, which is more commonly found in elderly patients due to compromised immune function, will induce microglial activation within the brain (Lemstra et al., The discovery of dystrophic microglia in human brain represents a critical step in conceiving the microglial dysfunction hypothesis because it raises the possibility that microglia are subject to senescence and degeneration (Streit et al., The morphological abnormalities that characterize dystrophic microglia have been described in detail before (Streit et al., With regard to the aforementioned neuroprotective roles of microglia, there are a number of interesting points to consider in terms of how deterioration of these neuroprotective functions could be critically important in the development of aging-related neurodegenerative diseases. Phagocytosis of debris by microglia is an essential cellular activity that ensures maintenance of a clean, debris-free brain parenchyma, and is conducive toward facilitating optimal interneuronal electrochemical signaling. A substantial decline in microglial phagocytosis due to cell senescence and/or degeneration would almost certainly contribute to NDD development (Neumann et al., For quite some time now the presence of increased brain iron and/or a disturbance in iron metabolism has been seen as a major factor contributing directly to free radical mediated neuronal degeneration (Jellinger et al., As mentioned, there is an increasing number of recent studies that suggest significant involvement of microglia in synaptic plasticity (Tremblay et al., As the brain’s innate immune system one might be inclined to think of microglia primarily as immunological defenders that fight invading microorganisms. However, in so doing one underestimates their importance as supportive and neuroprotective glial cells essential for helping to maintain neuronal functioning in the normal CNS and especially their crucial involvement in CNS repair and regeneration during injury and disease. We believe that microglial neuroprotection constitutes a most important aspect of the cells’ biological significance because it defines a single common denominator that contributes to improved understanding of CNS development, normal adult brain function, as well mechanisms of injury, disease, and repair. Specifically, with regard to aging-related neurodegenerative diseases, which represent one of the greatest challenges for biomedical science in this day and age, we think that the concept of CNS immunosenescence has considerable potential for advancing progress in terms of new and improved approaches toward treatment and prevention.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.


Diagnostic reproducibility and accuracy in cytology and histology are the main issues in Oncologic Screening of cervix, breast and colorectal cancer : it can be achieved by programs for quality assurance (QA). The slides set standard represents the most used method to compare diagnostic proficiency, the chance of interpreting microscopic digital photographs provided an interesting alternative to read conventional microscope slides.The whole digital slide observed in a computer screen is a third, interesting, option to reach the goal. In fact all the information on conventional samples are transferred into a file, easily archived, catalogued, duplicated or advice for quality control, but is especially available at distance and from multiple locations simultaneously with drastic reduction of time needed to achieve proficiency test reproducibility ., educational programs with integrated digital slides are poorly developed or proficiency tests for continuing education and professional updating are easily accessible.The production of digital slides with modern scanners is relatively simple and quick. All suppliers offer services into private or public networks server in the literature  and softA project on Virtual Microscopy and Digital Pathology has been conducted in Emilia-Romagna Region  with the goal to promote quality in diagnostic cytology and histology in Screening programs by testing a different system involving pathologists and cytologists using digital slides, with a faster and reproducible program easier to manage than standard diagnostic sets and by distance for retraining of patrhologists with a final consensus meeting.The aim has been reached with the realization of a management system for cytological and histological whole-slides digital images and related clinical data and the building of a picture archive and communication system (PACS) among pathologists of our (and probably other) region. This must be backed by software for the realization of network slide seminars to perform periodic diagnostic reproducibility and proficiency test. The cases, collected and properly catalogued in an online, easily accessible and systemic digital archive of slides, with diagnoses discussed in clinical and pathologic audit meetings and validated by experts, can be used as diagnostic reference tools (case registry online ). The cataloguing and indexing is performed with NAP codes derived from SNOMED , which cThe cancer screening group of the Emilia-Romagna Region  set up a picture, archive and communication system (PACS) devoted to pathologists for cooperative diagnosis, teaching and training, teleconsulting, documentation of rare cases and pilot experiences; furthermore selected cases are catalogued in the PACS with the aim to check the diagnostic concordance in regional oncologic screening . The PACS system is made by two Aperio scanner and an adequate internet server where the described programs perform, . An e-learning platform (Docebo)  has beenNowadays the diagnostic reproducibility has been performed in colorectal and cervical cancer screening , and for breast cancer is ongoing (Bologna June 2012). In all three slide seminars a number of cases have been selected by a committee of pathologists working in regional anatomo-pathologic units.Colorectal cancer screening was the first retraining slide seminar for pathologists performed with these features in our region and probably in Italy.Three regional units  were involved by sending representative histological cases of all main diagnostic occurrences to test the diagnostic reproducibility; 28 histological cases were collected. A definite and limited time interval was indicated to study slides, then a consensus conference was organized in the same day.The second Seminar of QA to test the diagnostic reproducibility was performed in cervical cancer screening program; 30 cytological and 30 histological cases have been selected by a committee of pathologists among the cases proposed by the regional units. All main diagnostic occurrences were represented, basic clinical information and relevant follow-up information were available; the cases have been completely anonymized.A 30 days interval was indicated to study the slides, then a consensus conference has been programmed at the end of the evaluation to present the results and discuss cases. Before the meeting each participant received a report with the gold standard diagnosis performed buy the committee and her/his diagnosis and concordance result.colon-rectal QA and the diagnostic reproducibility have been evaluated matching their results with the final gold standard diagnosis reached during the consensus conference. The observed agreement was 69% and the overall performance of the participating pathologists was assessed with a statistical analysis using Cohen’s kappa: the average value was 0.64 .15 pathologists of regional units attended the cervical cancer screening QA.95 cytologists and 32 histopathologists have been involved in the The diagnostic reproducibility has been evaluated using the final diagnosis reached in the consensus conference: in 2 out of 30 cytological cases the diagnosis was different from the diagnosis of the committee, while all histologic diagnoses were in agreement. The overall performance of the participating readers is reported in table Whole digital slide is suitable for proficiency tests and the internet e-learning platform allows to share cases and to get the answers from participants, in a easier way than by of a set of conventional slides.The quality of whole slides is very good, approaching optical microscopic resolution.In a cytological environment the bias is to get a perfect focus in all parts of the slide; the wider area of slide to examine and the higher number of diagnostic classes may justify a worse agreement of the pathologists and a poorer performance (lower Cohen’s kappa) than histology.We have produced an integrated environment that includes many of the modern aspects of digital pathology that can be shared with the PACS system in many laboratories of the region, including quality promotion and control of image interpretation in cytology and histology applied to cancer screening.


PopulatThe coding of single stimuli in population codes is relatively well understood , and in Theoretical studies  have thWe investigate the theoretical implications of these findings by comparing different encoding strategies and examine the decoding accuracy. The goal is to find the optimal encoding scheme for multiple stimuli.We investigate the theoretical implications of these findings by comparing different encoding strategies and examine the decoding accuracy. The goal is to find the optimal encoding scheme for multiple stimuli.In our current study, we focus on the simultaneous coding of visual stimuli representing overlapping movements of two groups of points in different directions. We investigate different ways of decoding these, among them a Maximum Likelihood decoder and estimate error rates made by these predictors, comparing to maximum rule to a linear rule.


To the Editor: Wagner and colleagues report nosocomial dengue transmitted by needlestick and note that it is the fourth case of nosocomial dengue to their knowledge (nowledge . In the nowledge . Three onowledge –5.We have recently published a case of nosocomial dengue infection that was transmitted by mucocutaneous exposure to blood from a febrile traveler who had recently returned from Peru . During We agree that nosocomial transmission may become more common in temperate areas as more travelers return home with acute dengue fever. As Wagner and colleagues pointed out, travelers visiting Southeast Asia have the greatest risk of acquiring dengue infections because of the high endemicity of these viruses there. Our report further illustrates the occurrence of dengue infection in the Americas  and the


This article has been republished to address equation and symbol formatting errors and errors in figure citations. This republication addresses the errors referenced in the previous formal correction. The publisher apologizes for the errors.


Type1 restriction modification system are intriguing multifunctional multisubunit molecular motors that can catalyze both restriction and modification activity. The type 1 RM enzymes binds to its target sequence and its activity as an endonuclease or methyltransferase is determined by the methylation state of the target sequence. If the target sequence is unmodified, the enzyme while bound to its target site is believed to translocate or pull the DNA towards itself simultaneously in both directions in an ATP dependent manner.The crystal structure of the motor subunit R has been determined by our group but the molecular mechanism by which these enzymes translocate and cleave the DNA is not fully understood.Our current research effort focuses on full-length three-dimensional structures of the R-subunit, utilizing computational and bioinformatics methods. Modelling of missing loops of residues of the crystal structure is done by Modeller9v2. Optimization of intersubunit contacts is performed by energy minimization followed by molecular dynamics simulations in solution at 300K. The dynamic behavior of WT and mutant holo and apo systems is explored by molecular dynamics simulation in GROMACS using the AMBER99SB force field. Conformational changes connected to coupling of translocation and endonuclease activity are observed and QM/MM methods are applied to calculate the contribution of the residue to the overall binding energy of ATP in the binding pocket.


The goal of this Research Topic was to bring together articles representing the spectrum of current research aimed at understanding the functional organization motor cortex at the level of microcircuits.The original research articles in this collection address a wide range of aspects of motor cortex microcircuits. The monkey's motor cortex is an especially important model system because of the similarities to the human brain, and the ability to train monkeys to perform complex movements. However, information about the cellular composition of different primates has been limited; Young et al.  now descin vivo dynamic activity across motor cortical layers in relation to movement. Harrison and Murphy (The review-type articles provide new syntheses of current knowledge about different aspects of motor cortex function and dysfunction. Kaneko  focuses d Murphy  emphasizd Murphy  address d Murphy  discussed Murphy  review dd Murphy  review ed Murphy  review tWe are impressed not only with the diversity of contributions included here, but even more so we were delighted that researchers from all walks of motor cortex investigation enthusiastically steered their research toward the microcircuit theme pursued in this volume. More than ever it seems clear that we all are working toward a common goal, i.e., describing motor cortical function in terms of the transactions in identified cellular circuits. We thank the authors for their contributions, and are additionally grateful to the many reviewers who contributed their efforts.


There has been a complete turnaround in scientific thinking about malnutrition as a protective factor to that of a major determinant of diabetes. Development of Type 2 diabetes is attributed to a combination of genetic susceptibility and precipitation factors in adult or early adult life. Current trials and preventive interventions are based on this gene-obesity model causing glucose intolerance necessitating food restriction for management. However when we compare the burden of low birth weight and intrauterine growth restriction with that of type 2 diabetes it can be hypothesised that good nutrition during intrauterine development and early childhood is more important. Foetal programming due to under nutrition can result in intergenerational transfer of long latency disorders.This hypothesis led to the establishment of the Pune maternal nutrition study and Pune children study involving cohorts. The Pune children study involving 400 children has completed 21 years of follow up and has shown an inverse relationship between birth weight and risk of diabetes mellitus measured by high glucose and high insulin levels. The maternal nutrition study which started with 2675 pregnant women in six villages has now completed 17 years. Both the mothers and children are being followed with very good follow up rates. The study involved consensus building among village leaders, consultation of experts, focus group discussions and training of local girls as Auxiliary Nurse Midwives (ANMs). The study involves assessment of weight and haemoglobin of young women, nutritional intake during pregnancy, foetal growth monitoring, biochemical assessments, storage of maternal and cord blood samples, detailed anthropometry at birth and continuing monitoring for cardiovascular disease risk markers. A steering committee of all stakeholders was constituted to oversee the study. The observations have shown that the intra abdominal fat content of Indian babies is higher. Low vitamin B12 levels, folate levels and high homocysteine levels are shown to be associated with low birth weight and insulin resistance in offspring. This demonstrates that maternal micro nutrient status influences risk of diabetes in the offspring and birth weight is a marker of intrauterine environment. Policy implications include ensuring the health of the young girl and addition of vitamin B12 along with folate for pregnant women. The biochemical estimation was made possible by storage of samples in biobanks which is a most useful resource for subsequent measurements, but there are ethical concerns and issues of subject approval.


Docking is possibly the most widely used technique in structure-based drug design. It is recognized as extremely useful to guide the development of active molecules as well as in virtual screening to identify new leads. But docking is also notoriously imperfect and many aspects need to improve. In this talk I will present our work on two different sources of errors in the docking predictions: protein-ligand interaction potentials and internal energy of the ligands. The use of higher-level calculations offers an opportunity to obtain better quality results and offers a glimpse of the full potential of the technique, but introducing this information back into fast and general scoring functions remains a challenge.


Several hypotheses have been proposed to explain the unexpected results of the first completed efficacy clinical trial of a vaccine against dengue virus C). This is distinct from vaccine efficacy against infection (VEI), and potentially a very important distinction.However, we believe that in addition to questioning the immune response elicited by the vaccine, it is important to discuss the interpretability of efficacy results for dengue vaccine trials that are based exclusively on clinical outcomes. The study by Sabchareon measured vaccine efficacy against clinically apparent infection  are equal in the control and vaccine groups.VEC and VEI. I would seem to be ineffective in a trial based only on clinical outcomes.Dengue disease is caused by four interacting viral serotypes. Risk factors for symptomatic disease have not been fully characterized. There is substantial evidence that preexisting, naturally acquired immunity against a heterologous serotype is a significant risk-factor for the development of clinical disease C and VEI under different assumptions of the impact of prior heterologous immunity on the probability of symptomatic disease, we developed an analytical framework  (C could lead to prematurely abandoning vaccines that could have promising population-level impacts or moving forward with an overly optimistic estimate of a vaccine's impact.To explore the agreement between VEdisease) . DiscardC and VEI also raises questions about one of the conclusion of this vaccine trial: that the “absence of any sign of disease enhancement…in the presence of non-protective immune responses” to DENV-2 serves as evidence against vaccine-induced enhanced severity of disease. With the inclusion of only clinical outcomes, it is impossible to know what number of individuals in the vaccine or control groups experienced infection and thus what fraction of infections experienced clinical outcomes. Tradeoffs between protective immunity and immunity that may predispose individuals to severe outcome again obscure the results.The discrepancy between VEC the primary measure of vaccines I will be necessary to determine the proportion of the population that needs to be vaccinated in order to control transmission. We acknowledge that measures of infection  are imperfect and resource intensive, but surveillance for infection has been performed routinely in other cohort studies While we agree with WHO guidance that clinical disease should be the primary end point of dengue trials and thus VEText S1C and VEI.Description of the analytical framework developed to explore the agreement between VE(PDF)Click here for additional data file.


The aim of the workshop is to explore the effects of footwear design on lower limb motion and discuss research findings relevant to the clinic and physical activity. Delegates will be actively involved in a motion capture process where important lower limb joint stress variables will be displayed in real time. The University of Sydney researchers will raise footwear issues from a range of areas such as children physical activity, adult walking and running, specific footwear such as thongs (flip-flops), dance and experimental methodology.During or on completion of this workshop, participants will be able to:• Critically analyse footwear characteristics that are likely to influence lower limb function during physical activity.• Experience the use of state of the art technology to analyse lower limb mechanics.• Discuss the models and methods used to build knowledge about the effect of footwear on lower limb mechanics.• Recount clinical and research outcomes for the effect of footwear on lower limb biomechanics during physical activity.• Apply biomechanical principles to the effective choice of footwear for a range of physical activities.


Eating disorders can be a life threatening illness not only due to the effects of starvation, but also the effects of impaired capacity. At Robina Hospital, patients admitted with a BMI < 14 are admitted to the Acute Medical Unit (AMU) for nutritional restoration and medical management before being transferred to a suitable mental health ward for ongoing treatment.The AMU at Robina has been managing patients with eating disorders, in particular Anorexia Nervosa for a number of years. The treatment plan implemented by the Acute Medical team is considered to be of a very high standard by the Eating Disorders Outreach Service (EDOS), a specialist consulting liaison service provided by the Royal Brisbane and Women's Hospital. The AMU prides itself on developing a cohesive multidisciplinary team approach, striving for best practice management by utilising protocols and guidelines developed by the EDOS service.This presentation will discuss the experiences of the Acute Medical Team in managing eating disorder patients. It will outline the team structure, current practices and guidelines used and identify areas of improvement recognised through lessons learned.The aim is to present information and experiences that may assist other acute inpatient medical settings in managing eating disorder patients discussing evidence based strategies developed to support and improve the management and physical health of patients with eating disorders.Care in Inpatient and Community Settings stream of the 2013 ANZAED Conference.This abstract was presented in the


For the past decade the field of proteomics has transitioned from a highly specialized research area into a conventional technique widely employed by plant biologists. This approach now encompasses basic protein identification to advanced comparative studies. The result has been an abundance of proteomics data, often not readily available to the research community  often represent the functional state of a protein and are a significant objective for many proteomic studies. A number of resources have been developed to interact with these phosphoproteomic datasets. Initial phosphoproteomic surveys involved Arabidopsis and one of the first phosphorylation-based databases created in any species was PhosPhAt (Arsova and Schulze, The proteomics community has created an array of online tools that can be used to support various technical approaches in mass spectrometry. The MRMaid utility was designed to facilitate the selection of peptides for targeted proteomic analyses (Fan et al., The range of proteome resources highlighted in this Research Topic reflect the diversity of proteomic-based applications in plant sciences. The principle objective for many these research groups has been focused on cataloguing or collecting data in an effort to capture information. Indeed, the creation of many data portals likely reflects an attempt to make sense of one's own data. This collection highlights the diversity and range of plant proteomic resources and utilities available to the plant research community.


Information regarding the first and last authors is incorrectly omitted from the Competing interests statement. The Competing interests statement should read: "One of the authors (Dr. Juhl) is affiliated with Indivumed, GmbH. A provisional patent application has been filed by Georgetown University related to the technology described in this paper. Drs. Wellstein and Shivapurkar are named as inventors on this provisional patent application.This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials and does not provide a conflict of interest."


More than 500 delegates and speakers from twenty countries gathered to hear about best practice and innovation in trauma care, pre-hospital care and major incident management. In addition the Norwegian Air Ambulance hosted a day devoted to air ambulance medicine and a parallel symposium examined key aspects of cardiac arrest. This produced to an expanded programme that appealed to a wide range of professional groups. This supplement describes some of the key points made by speakers and also focuses on two innovative aspects of training for penetrating trauma. Firstly resuscitative thoracotomy training for non-surgeons based on a one-day practical workshop held during the conference and secondly the training of young offenders to administer immediate care at the scene of injury – based on an abstract accepted for presentation. The posters and oral presentations submitted cover a wide range of subjects and the accepted abstracts are published at the end of this supplement. Dates for the 2013 conference can be found at http://www.londontraumaconference.com.The sixth London Trauma Conference was held at the Royal Geographical Society in London between 4


Information regarding a possible competing interest of the sixth author is incorrectly omitted from the Competing interests statement. The Competing interests statement should read: "James A. Colbert was an editorial fellow at the New England Journal of Medicine. Navindra Persaud is an Associate Editor for the Canadian Medical Association Journal. Peter Gill is a member of the Editorial Advisory Board of the CMAJ. All other authors have declared that no competing interest exists. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials."