Dang and colleagues recently reported in the journal that tumor response to definitive chemoradiation, as assessed using the RECIST criteria, and the risk of radiation pneumonitis were positively correlated in patients with non-small cell lung cancer (NSCLC). We had previously reported similar findings in a study that used positron tomography both to measure tumor response and to assess normal tissue toxicity in patients treated with chemoradiation for NSCLC. Taken together these reports suggest that radiosensitivity of normal tissues and tumors may be strongly linked in a proportion of patients with lung cancer. We read the recent article published in the journal by Dang and colleagues with interest . These a


The Editorial on the Research TopicMolecular Regulation and Therapeutic Potential of Thermogenic Fat CellsMuch of systemic metabolism depends on the activity and function of adipose tissue. Adipocytes in mammals fall into two categories classified by their primary functions: white fat cells that mediate energy storage and thermogenic fat cells that counteract hypothermia and obesity through adaptive thermogenesis. Whereas white fat and its function as an energy reservoir and endocrine organ have been studied for decades and are relatively well understood, until recently, many aspects of thermogenic fat biology have remained elusive.It has long been appreciated that the thermogenic brown adipose tissue that exists in the interscapular depots of small rodents, hibernating mammals, and human infants provides significant evolutionary advantages against cold stress . The lasPark et al.; Mueller; Bayindir et al.]. Reviews and a perspective article next explore how mitochondrial function, including redox homeostasis, is regulated within these thermogenic adipocytes . Central control of adaptive thermogenesis and other functions of thermogenic adipocytes are also highlighted . Importantly, several articles illustrate that interconnections exist between adipose tissue function and overall metabolic health, and how to increase the content and activity of these cells to ultimately fulfill their therapeutic potential in humans . As technology has advanced, novel interdisciplinary approaches have been developed to harvest the thermogenic capacity in fat tissue toward the control of obesity and metabolic diseases . We anticipate that all these articles will help the scientific community, both experts in the brown and beige fat area and newcomers entering the field to understand the molecular mechanisms of brown/beige fat development and induction, and appreciate the physiological impact of thermogenic fat activity. I would like to thank all the authors and reviewers for their contribution and discussion to put together this wonderful topic that may inspire further interest in this exciting new field.In this research topic, leading experts in the energy metabolism field provide an overview of our current understanding of these metabolically active fat cells. We begin our discussions with mechanistic insights on the transcriptional regulation of thermogenic fat cells [JW conceived and wrote the manuscript.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Casemix Grouper software is a tool to improve efficiency and quality of care in hospitals and medical centres. The utilisation of Casemix Grouper among hospitals is very limited and depends on their existing local machine and hardware. While Casemix Grouper provides a crucial output in the form of Casemix groups, the hardware machine should not be a limiting factor to hospital. Thus, the objective of this development was to provide the utility for end user to use the Casemix Grouper on web environment.The conventional way of providing Casemix Grouper service is by deploying standalone software at user’s local machine. This will create problem when user’s machine are diverse and does not meet the requirement for running the Casemix Grouper. The online Casemix Grouper will have 2 modules, which are for user and for the admin. The user module includes the authentication login and then uploading the input file. Developing a web based using Java Servlet Page (JSP) will provide access to all the available browsers on any operating system, so that end user can upload the Casemix input file. After the input file has been uploaded, online grouper will process the input file and generate an output file. The user will receive the output file via user-registered email. The admin module will also have authentication login and will be able to monitor the whole process for each users.With the implementation of Casemix Grouper as a web-based application, user can now avoid the stringent hardware requirement on their local computers for standalone Casemix Grouper. The end users can now focus only on generating the input file and will receive output file without extra effort. This usage of web application of Casemix Grouper software will facilitate the provision of efficient and quality care in hospitals and medical centres.


When it comes to prevalidation, it is assumed that a higher preoperative level of physical activity leads to better postoperative recovery. However current literature is inconclusive about the effect of prevalidation on functional recovery of patients with primary osteoarthritis (OA) who underwent a THA or TKA. Therefore the aim of this study is to analyse one of the major assumptions underlying the potential effectiveness of prevalidation namely the relationship between preoperative physical activity level and postoperative recovery one year after THA or TKA in a group of 658 OA patients.From 2006 to 2012, 1061 patients underwent a primary THA or TKA at University Medical Center Groningen. Preoperative and one-year postoperative patients filled in the SQUASH questionnaire to get an impression of their physical activity level, and the WOMAC questionnaire to obtain insight into degree of recovery. Missing data were multiply imputed. No relationship was found between the preoperative total  and leisure-time physical activity level  neither for preoperative compliance with the Dutch Recommendation for Health-Enhancing Physical Activity , and the degree of recovery one year after surgery.The preoperative physical activity level had no relation with the degree of recovery one year after THA or TKA. The results do not support one of the major assumptions behind prevalidation, which assumes that a higher preoperative physical activity level will lead to a better recovery after THA or TKA. Based on the Dutch GP registries, osteoarthritis (OA) is the most common progressive disorder of the musculoskeletal system It is hypothesized that the amount of preoperative physical activity and thus the fitness level can have a positive effect on the postoperative recovery of patients undergoing THA or TKA. This assumption is based on the fact that physical activity, fitness and health are mutually influencing factors Objective of this study is to analyze one of the major assumptions underlying the potential effectiveness of prevalidation namely that the amount of preoperative physical activity and consequently the fitness level has a positive effect on the postoperative recovery of patients undergoing THA or TKA. Insight into this relationship can strengthen or weaken the arguments for using prevalidation as a tool to improve postoperative recovery. The main question in this research is: Is there a connection between preoperative physical activity level and degree of recovery one year after THA or TKA in patients with OA?This research question is divided into three sub-questions:Is there a connection between the preoperative total physical activity level and the degree of recovery one year after THA or TKA?Is there a connection between the preoperative level of leisure-time physical activity and the degree of recovery one year after THA or TKA?Is there a connection between preoperatively meeting the Dutch Recommendation for Health-Enhancing Physical Activity and the degree of recovery one year after THA or TKA?A retrospective cohort study of prospectively collected data was conducted. Patients were asked to fill in the SQUASH and WOMAC questionnaires preoperatively and one year postoperatively. Completion of the questionnaire was taken as consent to participate. The Ethics Committee of University Medical Center Groningen approved this study (METc 2013/259).All patients that underwent a primary THA or TKA at University Medical Center Groningen between 2006 and 2012 were included. Patients who got a THA or TKA because of primary OA and had no operation within the following year after surgery were included in this study.Level of physical activity and meeting the Dutch Recommendation for Health-Enhancing Physical Activity (NNGB) were measured with the SQUASH questionnaire Degree of recovery was measured with the WOMAC questionnaire. The WOMAC is a self-reported questionnaire that measures OA-caused constraints experienced by the patient in function and degree of pain and stiffness when performing daily activities. The total score is reproduced on a 100-point scale, where a higher score represents a lesser degree of perceived restriction in daily activities. The Dutch version of the WOMAC questionnaire is considered reliable and valid Statistical analyses were performed with SPSS20. Descriptive statistics were used to describe the main characteristics. Univariate linear regression analysis was performed to answer the research questions. A second forward stepwise linear regression analysis was performed, adjusted for several potential confounders: type of surgery (THA or TKA), sex, BMI, ASA class and age of the patient at the time of surgery. A p-value of <0.05 was considered statistically significant.From the 1061 patients who had undergone a primary THA or TKA, 658 were included (see The mean age was 68 years (SD 10.6), with more women than men (32%) and more THA than TKA (36%). The majority had finished a form of lower (22%) or secondary (50%) education see . One yeaThere was no significant connection between the total preoperative physical activity level and the degree of recovery one year after surgery , even after adjustment for confounders see .There was no significant connection between the leisure-time preoperative physical activity level and the degree of recovery one year after surgery either , even after adjustment for confounders see .No significant connection was found between preoperatively meeting the NNGB and the degree of recovery one year after surgery , even after adjustment for confounders see .The basis for this study is the lack of understanding of the connection between preoperative physical activity level and degree of recovery after THA or TKA. Available studies report conflicting results The results of this study are in accordance with recent reviews on the link between prevalidation and degree of recovery after THA or TKA A strength of this study is the relatively large group of 658 patients who had undergone THA or TKA. Because all THA and TKA patients in the registries of UMCG are included, no selection bias occurred. In many studies on the effect of prevalidation a relatively large number of patients drop out during the study. Rooks et al. Overall it can be concluded that in this study preoperative physical activity level is not related to the degree of recovery one year after THA or TKA in patients with primary OA. It must however be taken into consideration that in this study the level of recovery was measured at one single moment, namely one year postoperatively. Patients are generally considered to have completely recovered one year after THA or TKA, yet this offers no insight into the connection between preoperative physical activity level and speed of recovery. Whitney et al. S1 DataMultiple imputed dataset.(SAV)Click here for additional data file.


The magnitude of the neural activation, and hence the force produced by a muscle, depend on the number of motor units activated (recruitment) and the rates at which motor neurons discharge action potentials (rate coding). Although the recruitment order of motor units (size principle) is similar for contractions during which the force is gradually increased (ramp contraction) and those during which the force is produced as fast as possible . An alternative way is to produce force as fast as possible but to relax the muscle immediately after the target force is reached. Such impulse-like contractions have been termed Desmedt and Godaux  were theThe discharge characteristics of single motor units during ballistic contractions can be modulated by the conditions under which the action is performed. For example, it has been observed that when a ballistic contraction with the ankle dorsiflexors was superimposed on a submaximal isometric contraction , the average discharge rate for the first three interspike intervals was significantly reduced by 22%  compared with ballistic contractions performed from a resting state  than in young adults (~20 year) (Klass et al., To further analyse the effect of a change in discharge rate on the maximal rate of force development, isometric force produced by single motor units was simulated from a model that contains a pool of 200 units (Fuglevand et al., Together, experimental and simulated data indicate that a high initial motor unit discharge rate at the onset of a fast contraction plays a critical role to reach a high rate of force development. Furthermore, and because the instantaneous discharge rates of motor units at the onset of ballistic contractions are much greater than those recorded during slow contractions and not yet influenced by history-dependent effects, ballistic contractions from a resting state can be used to assess the maximal motor neuron discharge rate in human. Nonetheless, as the acquisition of a simple motor task such as index finger abduction requires up to ~300 repetitions to reach maximal acceleration capability (Lee 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 study aims to explore a unique resource of weight and health data for further studies on effects of body weight and body condition score on developmental degenerative and metabolic diseases in dogs.Our study-data on weight at 12 months of age for more than 100,000 dogs of various breeds from the dog database at the Swedish Kennel Club (SKK) have enabled us to:– provide a reference for further studies by characterizing distribution of adult body weights in various breeds, also stratified by other factors, e.g. sex.– explore how weight influences hip and elbow status recorded in the same database.– investigate how to combine these data with recording of body condition score and to merge them with diagnostic information as insurance claim data.There is a wide range of body weights within all analyzed breeds as well as between the sexes within breeds. There is a pronounced correspondence between body weight at 12 months of age and radiological status of hips and elbows. It is also possible to include body condition score in further analyses and also to merge the data with anonymized information from an insurance claim database.We showed that the available body weight data are well-suited for further studies on the role and effects of both weight and body condition score in various diseases in dogs.


A binge eating episode is defined as an uncontrolled event of hyperphagia, in which people quickly eat a large amount of food while feeling a sense of loss of control over eating  pellet for 2 h  plays an essential role in the regulation of eating as it is highly sensitive to peripheral signal molecules of energy status , which project to the nucleus accumbens (NAc) in the ventral striatum and other areas such as the amygdala, medial prefrontal cortex, hippocampus, and hypothalamus Kenny, . The VTAThe homeostatic and hedonic circuits regulating eating are presumably integrated in the lateral hypothalamic area. This area contains orexin neurons highly innervated by hypothalamic and mesolimbic circuits that project widely within the brain (Schwartz and Zeltser, Clinical reports stress the complexity of assessing if an event of hyperphagia is actually a binge eating episode in humans (Wolfe 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 text describes the process of development of the new Spanish Prehospital Advanced Triage Method (META) and explain its main features and contribution to prehospital triage systems in mass casualty incidents. The triage META is based in the Advanced Trauma Life Support (ATLS) protocols, patient’s anatomical injuries and mechanism of injury. It is a triage method with four stages including early identification of patients with severe trauma that would benefit from a rapid evacuation to a surgical facility and introduces a new patient flow by-passing the advanced medical post to improve evacuation. The stages of triage META are: I) Stabilization triage that classifies patients according to severity to set priorities for initial emergency treatment; II) Identifying patients requiring urgent surgical treatment, this is done at the same time than stage I and creates a new flow of patients with high priority for evacuation; III) Implementation of Advanced Trauma Life Support protocols to patients previously classified according to stablished priority; and IV) Evacuation triage, stablishing evacuation priorities in case of lacks of appropriate transport resources. The triage META is to be applied only by prehospital providers with advanced knowledge and training in advanced trauma life support care and has been designed to be implemented as prehospital procedure in mass casualty incidents (MCI). Mass casualty incidents (MCI) are defined by World Health Organization as events which generate more patients at one time than locally available resources can manage using routine procedures . A recenMost of these triage methods are based in basic life support techniques and have been designed to be applied by rescue teams and firemen . The speModelo Extrahospitalario de Triage Avanzado) as well as its main features and field operating mode in a mass casualty incident. It should be noted that META is a method of advanced triage type to be used only by advanced prehospital providers with adequate training and education in advanced trauma life support protocols and techniques.The aim of this paper is to present the development process and design of the Spanish prehospital advanced triage method  during a MCI.During the second phase of the study the degree of perceived usefulness and feasibility of use in the setting of an MCI were analyzed for each of the selected parameters by a sample of health professionals of the Spanish healthcare system. To do this a survey was designed for doctors and nurses working in hospital emergency departments and prehospital emergency care systems in which they were asked to evaluate three dimensions for each parameter: (i) Ability to predict the patient’s vital risk, (ii) Ability to prioritize patient evacuation and (iii) Feasibility of use of the parameter in the prehospital setting in case of MCI. To assess the relevance of each parameter a numerical scale from one (irrelevant) to ten (maximum relevance) was used in each of the three dimensions.Once studied the degree of perceived usefulness and feasibility of use of each parameter during the third phase of the study, a wide panel of experts from different backgrounds  finally decided the parameters to be included in the triage method and sequence of application of each parameter during the triage process.anatomical type parameters, 19 were physiological type parameters, nine were parameters related to the kind of injury and nine were related to other conditions or circumstances of the victim or the MCI different of those already mentioned. Forty-five parameters were identified in literature review as potentially usable in an MCI advanced triage method. Eight out of those 45 identified parameters were p <0.05) for potential inclusion in the META. Table Seventeen out of the 45 parameters studied were found to be significantly relevant 3).Fig. 3Identification of need of urgent surgical care. The aim of this stage (applied at the same time as first stage) is to identify patients who do not benefit of complex prehospital care and needs rapid transport to a surgical facility. This creates a new flow of patients that will by-pass advanced medical post and will be directed to evacuation area with a minimum acceptable care. For these purpose we used the Guidelines for field triage of injured patients developed in 2011 by the National Expert Panel of Field Triage . These rAdvanced Trauma Life Support. All patients, once classified will be treated following advanced trauma life support protocols . Red patEvacuation triage. Once we have treated out of hospital emergencies on the field, we have to decide, in a scarced resources situation, which patient needs to be evacuated first. The first ones will be those with urgent surgical care need that have not been detected prior to evacuation. Then, we have define a new cathegory as “hight priority criteria” for those who have severe injury with haemodynamic or respiratory instability and one of these: systolic blood pressure under 110 mmHg , motor GMETA triage is to be implemented during the medical prehospital response to an MCI and has four stages: 1) Stabilization triage, 2) Identification of need of urgent surgical care, 3) Advanced trauma life support techniques and 4) Evacuation triage (Fig. The selection of the variables identified as potentially be incorporated to an advanced triage method is based primarily on well-known aspects of the clinical approach to prehospital treatment of patients with severe trauma, as well as in physiological, and anatomical aspects and the mechanism of injury. Once evaluated by doctors and nurses, parameters with higher scores are those related to physiological aspects. We decided to design a method based in the ATLS protocol but with an anatomical component that creates a new high priority category for those patients that benefit from rapid transport to a surgical facility.This new model of triage would be useful specially for EMS staffed by doctors or nurses, but also for EMS based in paramedics with an advanced education, knowledge and skills in the management of patients with acute severe trauma. Most of the well known triage methods do not fulfil the principles of the advanced trauma life support. In the above triage methods , for exaIn a MCI with overwhelmed healthcare resources the flow of patients at different stages of the medical response is often slow. This means that patient transportation may be delayed and for some patients this could be life threatening . This isOnce a patient is treated or stabilized should go to the evacuation point. In this point we go to stage four for evacuation triage. This last triage allows us to use available transport resources in the best possible way. In case of lack of transport resources patients classified as red have the highest priority for evacuation. These “high priority criteria” allows us to distinguish different priorities among patients classified as red and are based in a combination of clinical elements and injury mechanisms in order to improve evacuation of severe patients. This new method of advanced triage is highly adaptable to future scientific findings related to prehospital care and organization of MCI.One of the strengths of triage META is that has been developed taking into account the perception of emergency services staff on the factors to be considered in a method of triage and this is an important aspect that influences the success in implementation in daily work. Also the varied background of the expert panel has made possible a broad discussion on the different aspects and perceptions of the management of trauma care in the prehospital heathcare of MCI. Triage research has many limitations and is very difficult to fulfil the best evidence recommendations . Our metTriage META is a model of advanced prehospital triage and is a tool to be used by doctors and nurses trained as providers of advanced trauma life support, but also by paramedics with advanced education, knowledge and skills in management of patients with severe acute trauma. It can be implemented into MCI procedures and one of the main contributions is the early detection of severe surgical patients that benefit from rapid transport to a surgical facility. This mean that two flows of patients are needed in order to avoid delays of transport in these patients.Anatomical ParamethersAmputation proximal to the wrist or ankleTear or crushing of limbsOpen or depressed skull fracturePelvic fractureProximal fractures of two or more long bonesPenetrating woundContused woundFlail chestPhysiological paramethersHeart RateRespiratory ratePrehospital intubationLevel of consciousnessParalysisCarotid PulseRadial pulseVentilationAirway obstructionOxygen saturationSystolic blood pressureStaringPediatric Evaluation TriangleSpotted, pallor or cyanosis of the skinRespiratory distressStridor, grunting or breathing soundSpeech disorder or cryingFlaring nostrilsInteractivityMechanism of injuryKnive njuryFirearmOutrageFallRescue time more than 20 minutesEjected from vehiclePresence of a died person in the same vehicleVehicle IntrusionMotorbike accidentOthersMedical CriteriaOvertriage if case of doubt regarding severity of the patientAge under 15 or over 55Pregnant more tan 20 weeksSevere kidney diseaseLimb injury time dependantBurnsSexHaemostatiuc disorder or anticoagulants treatment


Metabolic flux comprises the ultimate phenotypic readout of cell physiology, and it shifts toward anabolic or catabolic regimes in conjunction with the proliferative state of the cell. Many parallels exist between the metabolic profiles of normal dividing cells and cancer cells, for which uncontrolled proliferation is a hallmark. Much effort in the field of cancer metabolism has been directed toward identifying these similarities to target how tumors use biochemical resources for growth and survival.Many studies have approached this question by experimentally identifying major metabolic changes that become induced in response to expression of oncogenes or inactivation of tumor suppressor genes; however, in these circumstances, the generality of these changes beyond the system under consideration may be unknown. Other avenues have employed genome-scale models of tumor metabolism to determine enzymes through which flux is upregulated when biomass production is maximized, but the size of these networks limits routine analysis.All major components of macromolecules may be derived from a small set of central metabolites that originate from well-known metabolic pathways, and as a result, it is possible to determine the rates at which these precursors must be consumed to maintain a particular growth rate. We have therefore employed a method to reduce experimentally measured biomass components to this set of precursor metabolites to better understand the effects of growth on metabolism in mammalian cells. Our strategy enables generalization of biosynthetic demands in a manner that is not specific for any particular oncogenic genotype while using a limited biochemical currency that enables elementary calculations and predictions.


Cold water immersion is a severe challenge for humans. Mathematical modelling of human thermoregulatory responses is an alternative approach to study cooling in water. Preliminary modelling prediction can be a useful tool for preventive steps that will help to decrease or even to avoid health hazard . The purThe complexity of multi-compartmental models for human thermoregulation is realised as Information Technology (IT) in Borland C++ Builder 2010 [Modelling Figure  showed tModelling showed that evaluation of the safe time of human immersion in cold water depends on what part of body is immersed. Head out of water has principal effect on core cooling rate . ModelliModelling prediction showed that thermoregulatory system is high sensitive to the immersion level of human in cold water. Surface out of water increases safe time of immersion. But head submersion has priority effect on core cooling. The results, when validated in all ranges, can be used for planning of rescue operations and development of protective clothing.


Systems Biology & Systems Medicine represent those emerging sciences. The development of the “Virtual Patient Avatar” will change conventional medicine into "predictive medicine" that will have the capacity to develop solutions based upon understanding of the dynamic mechanisms and the quantitative logic of human physiology. Drug discovery and clinical trials in silico will improve the development of products with higher efficiency and safety while reducing cost. Thus strategy must occur in the European Union to bridge the gap between academic and industry in the following ways:The integration of molecular sciences and computational sciences is moving the world towards a new generation of life science where physiological information from the human can be quantitatively described • Validate and publish medical informatics data and technology models to accepted standards in order to facilitate adoption,• Transform electronic health records to make them more accessible and interoperable,• Encourage information sharing, engage regulatory agencies, and• Encourage increasing financial support to grow and develop translational biomedical informatics.


It is believed that in many cases Food allergy (FA) develops due to the contact of the immune system with different allergens through affected skin and mucous barriers. Studies of the filaggrin mutations in atopic dermatitis showed informativity of the transepidermal water lost measurement (TEWL) in assessment of the skin barrier condition. Faecal calprotectin is marker of the inflammation that can be helpful in understand of the GIT mucous condition.To investigate a possible relationship between the TEWL and stool calprotectin level as markers of the barrier's deficiency with severity of the FA and treatment response.80 patients with skin symptoms of food allergy of different severity were under study. TEWL level, faecal calprotectin level were measured to identify the presence of the skin and mucous barrier's deficiency in children and it's change under treatment.High TEWL was associated with a more severe disease course and a poor response to treatment with antihistamines than in patients with less TEWL . Faecal calprotectin was elevated in 35/80 patients (43.7%) and was found to be significantly higher in patients with more severe FA symptoms (P<.05). Not all patients with positive stool marker (45.7% 16/35) noticed unsteady stool in anamnesis. In addition, the most effective influence on the severity of the TEWL had topical treatment with emollients, than oral intake of the antihistamines .TEWL and faecal calprotectin level measurement are simple and informative tests for FA course assess. Patients with FA and deficiency in skin and mucous barrier experience a more severe course of the disease and show a poor response to treatment with antihistamines. In this case it was proposed to use TEWL and faecal calprotectin level measurement as additional tests to reveal and predict possible ways of the further Atopic March in children. Topical treatment with emollients is more effective than oral intake of the antihistamines.


In literature, the most effective timing for intercepting skeletal malocclusion is still widely debated. The aim of this study was to analyze the main orthodontic and occlusal problems needing correction in growing patients.Crossbite, open bite and Class III malocclusion were observed and compared each one with their own control groups with the same age and dentoskeletal characteristics. The statistical comparisons between the test and control groups were performed with independent sample t tests and chi-square tests (P <.05).The presence of posterior crossbite was significantly greater in growing subjects with oral breathing thus confirming the influence of these factors on skeletal development with constriction of the whole palate. Unilateral posterior crossbite is often associated with mandibular lateral displacement that is clinically characterized by deviation of the chin, facial asymmetry, dental midline discrepancy, and high prevalence of internal derangement of the temporomandibular joint. Children with anterior openbite presented with a greater prevalence rate of sucking habits. Hyperdivergency is a risk factors for negative overbite in mixed dentition subjects. The test group had significantly smaller maxillary intermolar and intercanine widths and greater posterior transverse discrepancy. Class III malocclusion is a complex clinical entity that entail the contraction of the maxilla and a narrowing of the base of the nose in addition to an increased mandibular total length.Treatment of orthodontic problems that do not improve with age may be started earlier to avoid worsening of the condition in permanent dentition. The objective of any treatment in pediatric subjects before eruption of all permanent teeth are to correct the skeletal discrepancy between the jaws and improve function and facial esthetics by allowing them to develop normally, to create an ideal overbite and overjet relationship, to align the anterior permanent teeth and reduce the chance of trauma to these teeth, to improve the width of the dental arches and to reduce the risk for extraction of permanent teeth and for surgery in severe cases.Morphologic and functional characteristics of unilateral posterior crossbite with mandibular lateral deviation should be clarified to correct and prevent this malocclusion. Children with mouth-breathing pattern and sucking habits showed a significant constriction of the maxillary arch and an increased palatal height when compared with control group. Early treatment of Class III malocclusion is able to produce significant and favorable long-term skeletal shape changes characterized by an anterior morphogenetic rotation of the mandible.


Pilot and feasibility studies underpin much of current health related research, including randomised controlled trials. The number of reports in which authors describe their studies as pilot or feasibility studies is increasing and there is currently a lot of interest in this area. However, in spite of a number of papers that have recommended ways in which the reporting of these studies could be improved, reporting remains poor.Using CONSORT endorsed methodology including a large Delphi study (n=93) and an international consensus meeting (n=26) we have developed a CONSORT extension for randomised pilot and feasibility studies. Much of the existing CONSORT statement for randomised controlled trials does apply to these types of study. However, sometimes the application of the items is different from that in RCTs designed to evaluate the effect of an intervention or therapy and some CONSORT items are not applicable or have needed some alteration.We are currently writing the explanation and elaboration statement for this CONSORT extension. We will present the major issues in reporting these types of randomised studies and use examples to illustrate good and bad practice. This work is part of a larger programme of work on pilot and feasibility studies.


Life course socioeconomic inequalities in heart disease, stroke and all-cause mortality are well studied in Sweden. However, few studies have sought to explain the mechanism for such associations mainly due to lack of longitudinal data with multiple measures of socioeconomic status (SES) across the life course. Given the population health concern about how socioeconomic inequality is related to poorer health, we aim to tackle obesity as one of the prime suspects that could explain the association between SES inequality and cardiovascular disease and consequently premature death. The aim of this study is to test which life course model best describes the association between socioeconomic disadvantage and obesity among 60 year old inhabitants of Västerbotten County in Northern Sweden.t-test was used to compare BMI between advantaged and disadvantaged groups and one-way ANOVA was used to compare BMI among eight SES trajectories. We applied a structured modeling approach to examine three different hypothesized life course SES models  in relation to BMI.A birth cohort consisting of 3340 individuals born between 1930 and 1932 was studied. Body mass index (BMI) at the age of 60 and information on socioeconomic status at three stages of life  was collected. Independent samples We found sex differences in the way that late adulthood socioeconomic disadvantage is associated with BMI among inhabitants of Northern Sweden. Our study suggests that social adversity in all stages of late adulthood is a particularly important indicator for addressing the social gradients in BMI among women in Northern Sweden and that unhealthy behaviors in terms of smoking and physical inactivity are insufficient to explain the relationships between social and lifestyle inequalities and BMI.In order for local authorities to develop informed preventive efforts, we suggest further research to identify modifiable risk factors across the life course which could explain this health inequality. It is well-established that obesity is a major risk factor for mortality and morbidity and is on the rise globally . This toWhile the evidence for the contribution of life course SES to the development of weight change or obesity is generally strong , it remaThere has been a burgeoning literature in recent decades on the association between socioeconomic factors and total mortality and CVD risk factors in life course analysis using multiple measurements ,8. This Socioeconomic differences in mortality are well documented in most European countries including Sweden . People accumulation of risk model, the critical period model and the social mobility model. The most prominent model in the current literature is the accumulation of risk model, which assumes that cumulative adverse exposures during the life course increases the risk of CVD risk factors irrespective of the timing , as well as downward (D) adult SES mobility .The social mobility models (‘Late life mobility’ and ‘Any mobility’) showed particularly poor fits as they were significantly different from the saturated model . The general social mobility model assumes that all downward changes are equally harmful to health and that all upward changes are equally beneficial . This meWe note that smoking and physical activity are only two lifestyle aspects that are included in the analysis. Unfortunately, data on energy intake and food habits was unavailable. Even though we used a validated instrument to measure physical activity, it would be more accurate if it were not self-reported. Unhealthy behaviors including lack of physical activity  and smokOur study suggests that social adversity at all stages of late adulthood is a particularly important indicator for addressing the social gradients in body mass index among women in Northern Sweden and that unhealthy behaviors in terms of smoking and physical inactivity are insufficient to explain such association. In order for local authorities to develop informed preventive efforts, we suggest further research to identify modifiable risk factors across the late adulthood which could explain this health inequality. Our results suggest that efforts should be concentrated on reducing the social inequality that is associated with obesity in women in mid-adulthood and that such efforts should not be limited to targeting unhealthy behaviors.The authors declare that they have no competing interests.MN and MP participated in the design of the study. MP performed the statistical analysis and drafted the manuscript. Both authors read and approved the final manuscript.


This pictorial series illustrates four cases with interesting imaging presentations of some unusual primary and secondary breast malignancies and aims to exemplify the range of appearances of malignancy and stimulate discussion of atypical differential diagnoses in appropriate cases.We present a pictorial series of four patients with unusual breast pathology who initially presented to the triple assessment breast clinic in a tertiary university institution. For each case the imaging features and final diagnoses are critically appraised, along with a review of the literature. We illustrate a case reminiscent of bilateral invasive ductal carcinoma which, after further histological immune profiling, is confirmed to be the first presentation of a metastatic lung cancer. A sarcomatoid carcinoma presents as a densely calcified well-defined lesion on mammography accompanying a synchronous invasive ductal carcinoma and could initially have been seen as benign. We present the imaging features of a fibroadenoma which interestingly was shown to contain DCIS. We also highlight the appearances of a recurrent pleomorphic invasive lobular carcinoma within latissimusdorsi muscle following mastectomy and reconstruction.Interesting and unusual differentials for malignant breast lesions are presented pictorially with an emphasis on the initial presentation and imaging findings. It is hoped that this will both educate and stimulate discussion of differential diagnoses in the breast imaging setting.


Dental professionals have not fully embraced opportunities for tobacco intervention. The aim of my presentation is to suggest new strategy of curriculum to enhance smoking cessation intervention based on the novel findings that may useful under the universal health insurance system in Japan.Reviewed literatures regarding tobacco interventions by dental professionals and recent studies regarding oral microbiology, and surveyed dentists and dental patients to clarify the possibility of our strategy.The literature review regarding progression of the global dental tobacco interventions identified significant barriers such as lack of reimbursement and training for implementation to dental practice and dissemination and undergraduate education. Recent findings regarding the effects of smoking cessation on oral biofilms and those of tobacco extracts on virulence factor of periodontal pathogens would break the ice to enforce dental tobacco intervention in Japan. The studies that was conducted in dental clinics revealed that tobacco intervention for prevention of progression of dental disease and improvement of the effects of dental treatments that have potential coverage of the universal health insurance system in Japan were strongly supported by dentists while intervention services for prevention of oral diseases was strongly supported by dental patients.Education for dental students regarding tobacco intervention based on the effects on dental treatments would be promising strategy that reinforces those for oral and overall health in Japan.


While dissemination and implementation (DI) science has become a clear area of research focus with associated methodologies, grant programs, journals, and training programs, these are relatively recent developments which have created a gap in training and career development. Many large institutions with major research programs have some investigators who are carrying out DI research but these tend to be limited and many investigators whose work has relevance to the field are not trained adequately to take advantage of existing grant mechanisms. The University of Pennsylvania has taken the strategy of creating the Implementation Science Working Group (ISWG) with the goal of providing an opportunity for idea development, feedback, grant review, and review of key methodologic approaches and conceptual frameworks for the field. A key element of the ISWG has been to support pilot studies by faculty from across the university which focus on DI topics and which have potential for translation into NIH grant applications. In this presentation, we discuss current efforts of the Penn ISWG as an exemplar for other institutions, and present examples of pilot grant receipts who have received funding to conduct DI related work within the context of the university efforts to support DI capacity.


The significance of arterial lesions in IgAN patients has not been investigated well and characteristics of renal vessels in this disease not been studied separately. More investigations is necessary to found the clinical significance of thrombotic microangiopathy in IgAN.et al. in a study on a group of IgAN patients found 53% patients had morphologic lesions of TMA  have been completely observed by the authors.None.


Chronic inflammation in well-defined mouse models such as Giα2 knock out mouse has been shown to trigger formation and expansion of hypoxic niches and also leads to up regulation of NFĸB, offering cells which have adapted their genetic machinery to hypoxia a unique survival advantage. These adapted cells have been shown to acquire stem cell-like capabilities as shown by up regulation of stem cell markers. Such long lived cells become permanent residents in sub mucosa and acquire a malignant phenotype from long-term exposure to noxious environmental agents due to a barrier defect secondary to down regulation of barrier proteins such as Zo1 and Occludin. Indeed mitotic spindle disorientation in such mice has been proposed as another contributory factor to malignant transformation. Sterilization of bowel lumen of these mice through different techniques has prevented malignant transformation in the presence of chronic inflammation. These facts stand strongly against chronic inflammation as a true driver of carcinogenesis but clearly support its role in facilitating the emergence of the neoplastic clone. The malignant transformation as per the free energy concept necessitates a significant and permanent decrease in the free energy of the malignant cell as a result of breakdown of the fine balance of cellular energetics. WarburgThere are many examples in which chronic inflammation is associated with carcinogenesis. However in none of them there is solid proof of a driver role for chronic inflammation,7. In caViruses can directly induce malignancy by down-regulating tumor suppressor genes such as TP53 and Rb. Through this mechanism papilloma virus promotes the pathogenesis of malignancies such as squamous cell carcinoma of cervix and head and neck. The lisV617FJAK2 mutation in a hematopoietic stem cell is seen in the majority of patients with MPN. V617FJAK2 confers upon hematopoietic progenitors resistance to the suppressive actions of TNF. An environment with high levels of inflammatory cytokines (such as TNF) selects for cells which have mutated in such a way to avoid these suppressive cues (such as the V617FJAK2 neoplastic clone). The V617FJAK2 mutant clone then expands and leads to unrestrained expansion of mature myeloid cells. The V617FJAK2 neoplastic clone in MPN likely also induces an inflammatory state which further enhances its selective advantage. This inflammatory response elicited by the V617FJAK2 clone may also be required for clinical manifestations of the disease. Clones with leukemia-associated mutations (such as V617FJAK2) can be detected in a few percent of normal aged individuals[There is also evidence that chronic inflammation facilitates clonal evolution in myeloproliferative neoplasm (MPN), a chronic hematologic malignancy. Chronic inflammation is a characteristic feature of MPN and has been implicated as the cause of many of the debilitating symptoms associated with this disease. Emerging evidence suggests that inflammation may play a more central role in disease initiation and maintenance of the neoplastic clone16. Somatic acquisition of a There is evidence supporting inflammation as a tumor growth promoting but not initiating factor. One example is infiltration of glioma associated macrophage/microglia (MG). In CNS inflammation, MG have been shown to be capable of presenting antigens and activating T cells, thus playing a direct role in modulating brain inflammation. A signiOne could arbitrarily categorize malignant disorders into two major groups. The first group would be those malignancies that are driven down an inflammatory path, such as the examples mentioned above. The second group would be those malignant disorders that are driven down the non-inflammatory path, such as certain well defined syndromes including Li-Fraumini and Lynch syndrome, classical lung, breast and colon cancer among many others.Free energy was first described by the American engineer Willard Gibbs in 1873 as the amount of energy available to do non-volume increasing work in a system with constant temperature and pressure and that inversely correlates with the amount of entropy of that system on thermodynamics arrow of time.Biological systems including a living cell are well known for their unique capability to keep entropy at the lowest possible level dictated by the limits of the second law of thermodynamics. The breakdown of this fine balance which is the distinguishing hallmark of malignant disorders could be envisioned as the universal driving force capable of driving down both inflammatory and non-inflammatory roads of malignant transformation. The fine balance of the cellular energetics under normal condition is governing a broad spectrum of fundamental biological events extending from epigenome to Micro RNA network and incorporating dynamics of mitosis and homeostasis of cell cycle kinetics to DNA damage response and gene regulatory mechanisms,27. EvenInterestingly enough even the contemporary literature has started to appreciate the interplay of metabolomics and inflammation. LiteratAccording to the universal free energy concept normal inflammatory cells with normal metabolism and energetics get attracted to the tumor sites comprised of a significant number of cells with significantly lower free energy/lower in situ vibratory motion. This atAlthough chronic inflammation has been noticed and reported for a long time by many different observers both in the vicinity of malignant cells and at the premalignant lesions of a wide range of malignant disorders both of hematological and solid subtypes, assigning a driver role to chronic inflammation has faced insurmountable technical as well as evidence based barriers.CCL2 expression on the surface of glioma cells which attracts macrophages to the tumor site, with its ensuing activation of other components of immune system through secretion of humoral factors on one end and eradication of inflammation without any observable effect on tumor growth and progression on the other end, are among the examples that take away the designation of driver role from chronic inflammation in inflammation associated malignancies.Available evidence supports a promoting role for chronic inflammation following malignant transformation. Interestingly enough at times the malignant cell itself is the source of chemokines which attract the inflammatory cell to tumor site as mentioned above. Finally In other tumor types the malignant cells take advantage of the nurturing microenvironment of the immune system organ, namely lymph nodes before progressing into advanced stages. Melanoma and breast carcinoma are among such malignancies.The modern generation of immunotherapy, including CTLA4 and PD-1 antagonists, has enabled us to make clinical achievements and prolong the life of patients with metastatic melanoma.However the toxicities associated with these treatment modalities which originate in reacting against the self-antigens at times have proven prohibitive. The key question is if the immune system can recognize the difference between the energetics of the tumor cell and normal cell, why is it so incapable of destroying tumor cells and in addition why does it contribute to promotion and progression of malignant phenotype?The answer to this question might reside in the exceptional capability of the tumor cell to also change the energetics of the infiltrating immune cells in favor of a low free energy state which would disable these cells as a result of modification of the quaternary structure of its constituent functional proteins under low free energy condition, in addition to taking advantage of their growth promoting humoral factors. A new wave of improved understanding and design of delicate measurement devices of cellular energetics and the ability to reverse those differences offers hope for future cancer therapeutics modalities. Indeed even today we are witnessing a crude, however rewarding attempt at physical rather than chemical cancer therapy by alternating electrical fields in the treatment of recurrent Glioblastoma multiforme, called NovoTTF-100A system which has been misunderstood as only a change in electrical field of cancer cell without appreciating the induced transient increase in free energy of the cancer cell,33.


Dear Editor,Chronic patellar tendinopathy is a common clinical condition that is managed by physical therapists and is common among athletes and non-athletes alike. Patellar tendinopathy is characterized by the absence of inflammatory cells and prostaglandins and an increased presence of fibroblasts and disorganized collagen . Therefo


The study proves that simple image and depth sensors can be used to efficiently record biomedical multidimensional data with sufficient accuracy to detect selected biomedical features using specific methods of computational intelligence. The achieved accuracy for non-contact detection of breathing rate was 0.26% and the accuracy of heart rate estimation was 1.47% for the infrared sensor. The following results show how video frames with depth data can be used to differentiate different kinds of breathing. The proposed method enables us to obtain and analyse data for diagnostic purposes in the home environment or during physical activities, enabling efficient human–machine interaction.This paper is devoted to a new method of using Microsoft (MS) Kinect sensors for non-contact monitoring of breathing and heart rate estimation to detect possible medical and neurological disorders. Video sequences of facial features and thorax movements are recorded by MS Kinect image, depth and infrared sensors to enable their time analysis in selected regions of interest. The proposed methodology includes the use of computational methods and functional transforms for data selection, as well as their denoising, spectral analysis and visualization, in order to determine specific biomedical features. The results that were obtained verify the correspondence between the evaluation of the breathing frequency that was obtained from the image and infrared data of the mouth area and from the thorax movement that was recorded by the depth sensor. Spectral analysis of the time evolution of the mouth area video frames was also used for heart rate estimation. Results estimated from the image and infrared data of the mouth area were compared with those obtained by contact measurements by Garmin sensors ( Recently developed computational technologies enable the use of non-contact and non-invasive systems for monitoring breathing features, detecting heart rate changes and analysing facial features as important diagnostic tools for studying neurological and sleep disorders, assessing stress and evaluating fitness level ,5,6,7,8.Complex monitoring of selected biomedical features can be based on processing of data  recordedThe present paper is devoted to (i) the description of methodology for breathing and heart rate monitoring based on image, depth and infrared video sequences acquired by MS Kinect in the face and chest area; (ii) the visualization of the obtained data; and (iii) the comparison of biomedical features evaluated from data recorded by non-contact image and depth sensors.The proposed methodology assumes the use of digital filtering methods for data noise component rejection, resampling, data fusion and spectral analysis for detecting the required biomedical features. Specific statistical methods ,31 are aThe paper provides motivation for further studies of methods related to big data processing problems, dimensionality reduction, principal component analysis and parallel signal processing to increase the speed, accuracy and reliability of the results. Methods related to motion recognition can be further used in multichannel biomedical data processing for the detection of neurological disorders, for facial and movement analysis during rehabilitation and for motion monitoring in assisted living homes ,33,34. FThe sequence of separate images was recorded with associated time stamps indicating the video frame rate changing from 7 to 15 fps. Image resolution was 1920 by 1080 pixels while the depth and infrared camera resolution was 512 by 424 pixels. The video camera allowed following colour image components with selected results recorded at the mouth area of the individual as presented in Simple tests were limited by the data size that was obtained. By scaling the image data by a factor of 0.4, the 120 s record of data from the image, depth and infrared sensors occupy 1.2 GB of hard disk space. The overnight record of sleep activities requires about 250 GB of disk space and is dependent on the frame rate and resolution; specific methods of big data processing should be applied to reduce the evaluation time.Time stamps recorded with each video frame allowed resampling of the video sequence ,41 to a uisition .R rows and S columns that covered either the mouth or the chest area of the individual. For each matrix n, the mean values were evaluated by the following equation:The sequences of image and depth maps that were acquired by the MS Kinect were analysed over the selected rectangular area of N. To optimize the final algorithm, the resampling mentioned above was applied to this sequence only and not to the complete image frame in this case.In this way, the mean value of pixels in the selected area for each video and depth frame formed a separate time series M (=40) was then applied to each obtained signal to evaluate the new sequence Finite impulse response (FIR) filtering filtering of the selected order Spectral components in each recorded frame were then evaluated by a discrete Fourier transform forming the sequenceP using the least squares method to minimize summed squared differencesK values of spectral components The local polynomial approximation of evaluated spectral components was then applied in two specified frequency ranges corresponding to possible frequencies of breathing  in this record as presented in A general methodology for the estimation of respiratory rate and heart rate is presented in Analysis of the heart rate estimate based upon a 180 s infrared video sequence is presented in Different spectral components estimated in separate subregions over the whole period of 180 s are presented in The average range of chest movement in selected grid points and over the selected time of 120 s is presented in Final parts of each record in MS Kinect provides a cheap alternative to video monitoring of sleep abnomalities performed in sleep laboratories by polysomnography as the gold standard diagnostic tool. Polysomnography (PSG) records different biosignals, but it is an invasive method that may disturb natural sleep. In comparison with other efficient methods, including infrared video monitoring , it is pThis paper presents the use of MS Kinect image, depth and infrared sensors for non-contact monitoring of selected biomedical signals, evaluation of breathing and heart rate using recorded video frames, and verification of the obtained results. It is assumed that estimated features obtained from data retrieved from a natural environment will increase the reliability of such observations related to the diagnosis of possible neurological disorders and the fitness level of the individual. The purpose of this approach is to replace wired sensors by distance monitoring, allowing more convenient data acquisition and analysis.Obtained data were used for the analysis of biomedical signals recorded after specified body activity. The results show no significant difference between biomedical features obtained by different biosensors and non-contact MS Kinect technology. While breathing rate can be recorded with high reliability, non-contact heart rate detection depends upon the visibility of an individual’s blood vessels in the case of video sensor use.Results show how the MS Kinect sensors and selected digital signal processing methods can be used to detect the heart rate and to analyse breathing patterns during different kinds of breathing. Processing of video frames acquired during interrupted breathing points to the possible use of these sensors for sleep apnea analysis as well.The methods described here form an alternative approach to biomedical data acquisition and analysis. Developing the abilities of different biosensors with possibilities of wireless data transmission increase the importance of remote data acquisition and signal analysis using computational intelligence and information engineering in the future. This approach has a wide range of applications not only in biomedicine but also in engineering and robotics. Specific applications based on analysis of depth matrices allow gait analysis and early diagnosis of locomotor system problems.Further research will be devoted to algorithms for more precise data acquisition and processing to detect biomedical feature changes for correct diagnosis and for proposing further appropriate treatment. It is assumed that infrared sensors will be used for non-contact analysis during sleep to detect sleep disorders.


The increasing volume of existing information on biological processes and the use of large databases have significantly increased the accessibility of datasets to the scientific community. This has enabled performing an analysis to facilitate the extraction of relevant information or modeling and optimizing tasks in different processes. Parallel to the increasing volumes of information is the emergence of new or adapted distributed computing models such as grid computing and cloud computing. Together with new techniques of artificial intelligence, or more specifically knowledge discovery, these management systems are making it possible to perform a more efficient analysis of the information and are enabling the creation of adaptive systems with learning ability.In the area of distributed artificial intelligence models for knowledge discovery in bioinformatics, ten interesting proposals are presented. These models analyze different biological aspects and simulate the process or user behavior in the health care system. The main characteristics in these proposals are the use of artificial intelligence techniques to analyze the information and extract knowledge.“Bladder Carcinoma Data with Clinical Risk Factors and Molecular Markers: A Cluster Analysis” provides interesting research about bladder cancer. The paper shows the hypothesis that the use of clinical and histopathological data with information about marker is useful to manage treatments of nonmuscle invasive bladder cancers (NMIBC). The authors apply data mining techniques such as hierarchical clustering to create molecular cluster and risk groups. In their experiments, the authors analyze 45 patients with a new diagnosis of NMIBC. They create four groups of patients and categorize the patients according to clinical characters and biological behavior.The authors of “A Linear-RBF Multikernel SVM to Classify Big Text Corpora” use data mining techniques based on classifiers to big text corpora. In particular, they implement a variant of support vector machine (SVM) to reduce the computational cost. The authors show a multikernel SVM with automatic parameterization to improve the results of SVM parameterized under a brute force search. The proposal is composed of a workflow with algorithms to process documents, reduce the dimensionality of the data, and to apply/provide clustering, training, and prediction. The proposal is analyzed according to the classification results and building time in the dataset TREC Genomics 2005 corpus. Pleurotus ostreatus to improve quality and production. In order to carry out the analysis of the factors, the authors include several IoT sensors to retrieve the information from the sensors. The information is then processed with data mining techniques in cloud system in order to predict plant growth and manage plant growth control.In “Analysis of Environmental Stress Factors Using an Artificial Growth System and Plant Fitness Optimization,” the authors analyze how some environment conditions can accelerate the evolution process; in addition to modifying the environment conditions, it is possible to select genomic variants. The authors analyze several factors for“RecRWR: A Recursive Random Walk Method for Improved Identification of Diseases” proposes a new method to select the best disease targets for multiconcepts graphs. The proposal, referred to as recursive random walk with restarts (RecRWR), includes multilayer networks, graphs, and weights calculation and has been tested with the OMIM database with the area under ROC curves.“Gene Knockout Identification Using an Extension of Bees Hill Flux Balance Analysis” is an interesting paper that presents an extension of Bees Hill Flux Balance Analysis (BHFBA) integrated within the framework of the OptKnock and Hill Climbing algorithm in a local search to extract gene knockout in order to maximize the production of the desired metabolite. The proposal has been analyzed with different databases and compares the execution time, growth rate, and production yield. The authors validate that the BHFBA improves the performance due to the inclusion of the Hill Climbing algorithm.In “Using the eServices Platform for Detecting Behavior Patterns Deviation in the Elderly Assisted Living: A Case Study,” the authors present the eServices platform (Elderly Support Service Platform). The platform detects any deviation in the behavioral pattern followed by elderly people and is able to predict dangerous situations. The system was modeled with the CRISP-DM methodology and was tested with synthetic data based on real data and expert knowledge. The authors incorporate several data mining techniques such as decision trees, cluster, or ROC curves in order to validate the results.“Agent-Based Spatiotemporal Simulation of Biomolecular Systems within the Open Source MASON Framework” presents a tool for biomolecular reaction modelling in the multiagent simulator of neighborhoods framework (MASON). The tool describes the interaction among the molecules. The system is worth considering to analyze the effect of different factors in simulations. The system is tested in several scenarios based on enzymatic activity. The results area is compared with studies performed in laboratories.“A Distributed Multiagent System Architecture for Body Area Networks Applied to Healthcare Monitoring” presents an architecture based on a multiagent system to monitor the parameters of several users with biomedical sensors. The agents incorporate the BDI  model and data mining techniques to analyze the data of the sensors. The system is able to detect movements, activities, and postures. Its accuracy is confirmed and presented in the results taken from the tests performed in several cases.“Modelling the Longevity of Dental Restorations by means of a CBR System” presents a case based reasoning (CBR) system to analyze dental restorations with different materials. The system applies the steps of the CBR cycle in which it integrates several data mining algorithms to perform in the retrieved phase. It also includes a mixture of experts with neural networks and Bayesian networks in the reuse phase to predict the longevity of dental restorations. The system is tested with the data of patients and the results are shown in the paper.Finally, “aCGH-MAS: Analysis of aCGH by means of Multiagent System” proposes a multiagent system to analyze data of CGH (comparative genomic hybridization) arrays. The agents incorporate several layers to perform visualization and analysis and to manage information processes. The system proposes different visualizations to facilitate the visual analysis and to access the information in databases. Moreover, the multiagent system provides several data mining techniques to carry out the analysis. The system is tested with several kinds of CGH arrays and the results are shown in the paper.


Despite a large and rapidly expanding literature on psychological trauma, many fundamental questions remain about its basic nature: Is it a psychological problem or a biological one?; Is it a past event somehow stuck in the present or is it something new which has been triggered and shaped by that event?; Does it reside only within the patient or does it live between the patient and other people (including within the therapeutic relationship)? This presentation will review the history of the concept of psychological trauma and explore the theoretical bases for current evidence-based psychotherapies for PTSD, each of which will be shown to describe psychological trauma as a problem in bringing the past and the present together in memory and cognition. These theories primarily differ on the question of whether a traumatic memory becomes pathogenic, because it cannot be biologically processed or because it must be psychologically avoided. Psychoanalytic concepts of transference and countertransference will be shown to be of practical importance regardless of the type of treatment chosen. If researchers and clinicians can build on what they hold in common rather than become divided by their differences, we can improve our ability to understand and alleviate the effects of psychological trauma.


Scientific research into mental health outcomes following trauma is undergoing a revolution as scientists refocus their efforts to identify underlying dimensions of health and psychopathology. This effort is in stark contrast to the previous focus which was to characterize individuals based on Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic status  and allied methods such as Latent Class Growth Analysis (LCGA) for the identification of heterogeneous populations defined by their pattern of change over time will be presented .


Fukushima et al. recently published research on the relationship between cost sharing policies and medical spending by the elderly (Fukushima et al., One of the baseline results of the study claims: “lower cost sharing significantly increases medical spending.” This actually follows the natural logic that a patient is likely to consume more care if it is effectively free at the point of usage. Three decades ago policy makers believed it should be possible for a cost sharing mechanism to contain costs and induce net savings (Keeler and Rolph, The article conveys an important message with regards to the role of cost sharing in prescribing and dispensing medicines (Johnson et al., There is a variety of measures used to increase the prescribing of generics vs. originators in Europe. These include compulsory substitution, e.g., in Sweden (Andersson et al., The phenomenon of a shrinking labor force and threatened financial sustainability of health care provision was recognized in the Japanese market a few decades ago Ogura, . The devMJ has solely designed and authored this Commentary article without any external engagements by other contributor or professional services.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Polythelia has been defined as the presence of supernumerary nipples without accessory glandular tissue. Usually, these growths follow imaginary mammary lines running from the armpits to the groin.Although the presence of dental anomalies may occasion only a simple cosmetic problem with specific clinical considerations, the association with familial polythelia has been scarcely reported. This paper reports on a case of polythelia that is associated with dental anomalies in an Argentine family and discusses suggestions for a thorough dental history and medical consultation to prevent possible pathological conditions or potential malignant transformation of mammary tissues. The in,,,Polythelia represents a typical example of atavism and the word means "many nipples",The genetic transmission of polythelia appears to be heterogeneous and the most common modes are: autosomal dominant with incomplete penetrance and a dominant X-linked chromosome. Each of these modes has demonstrated intrafamilial variability in their clinical manifestations.Tooth agenesis is the most common anomaly of dental development and may occur as an isolated entity or that composing well-documented syndromes. These clinical situations appear to be due to chromosomal defects or mutations of the genes responsible for organogenesis ,,,Although the presence of dental anomalies may suppose a simple cosmetic problem with specific clinical considerations, the scantly referenced associations with polythelia (in syndromes of greater diagnostic complexity


Animals and humans must behave efficiently in acoustically rich environments, where few sound sources are of interest out of many others that are considered background noise. How does the auditory system implement such robust processing is a topic of intense research. In this work I am interested in the neural mechanisms underlying detection of novel objects in auditory scenes, such as a novel sound source at a given location.It has been shown psycho-physically that the perception of a sound depends on the acoustical context in which it occurs. A basic example of such effect is called enhancement . A harmoI implemented on the Brian simulator and its auditory package  a model The present functional study of auditory enhancement suggests that such contextual effects could be critical for animal survival and for hearing in realistic conditions. The results show how simple neural mechanisms modulate a sensory pathway so that it adapts to its surrounding environment and suggest that bias in perception could have ecological advantages. The model could also inspire the design of speech processing devices in real environments.


The combination of the acromion Open fracture to a section of the supraspinatus tendon is an exceptional situation. The author reports the case of a young patient with a wound of the posterolateral side of the right shoulder. Screwing was done for the fracture of the acromion after supraspinatus tendon suture with good clinical and radiological outcome after an appropriate rehabilitation. Open fracture of the acromion is an exceptional clinical entity and should be reported. A heavy stab wound was the cause of this exceptional lesion association in a young patient whose surgical exploration noted a supraspinatus tendon rupture with capsular break. The reconstruction of the acromial arch with rotator cuff repair was needed urgently under antibiotic cover and anti tetanus serum.The authors report the case of a 19 year old man; autonomous; right handed laterality; carpenter by profession; without medical or surgical particular history; victim of an accidental injury by a knife causing a wound from the outer side of the right shoulder. The clinical examination  objectifRadiographs  objectifA joint lavage was the first operative time. A careful closure of the joint capsule with absorbable suture followed by a suture supraspinatus tendon with a no absorbable suture by points X. An osteosynthesis of the acromion bone fragment by two 3.5 mm cancellous screws .The evolution marked by a consolidation of the fracture with complete functional recovery after a suitable rehabilitation shoulder started working early and the joint amplitudes and muscle strength .The literature review has not revealed a similar published case involving an open fracture of the acromion and supraspinatus tendon injury. The young person is more prone to this type of severe trauma to the shoulder and especially male , 2. The Scapula fractures are very rare; they represents only 1% of all fractures . In thisSeveral technics for fixation of fractures have been described acromion, including tension band wiring for more distal fractures, plate fixation for fractures that are more proximal or through the acromial base and spine, interfragment screw fixation, as the case of our patient, plate fixation supplemented with interfragment screws, and fixation with Kirschner wires. According to the DASH score functional outcome is very satisfying to 6 months after ablation materiel. No local complications were reported especially calcification or early or late infection.This is a very rare case that combined an open acromion fracture to a supraspinatus fracture. Care of this type of lesion should be emergency operated with a solid osteosynthesis and tendon suture for early and appropriate rehabilitation.


In an individually randomised controlled trial (iRCT) where the intervention is delivered by a health professional/therapist it seems likely that the effectiveness of the intervention could depend on the skill of the therapist delivering it. This leads to a potential clustering of the outcomes for the patients treated by the same therapist.If outcomes are clustered then the usual statistical methods for analysing RCT data may not be appropriate as they assume that outcomes observed on different participants are independent.In some iRCTs there is clustering in only one arm; where the therapist only treats participants in one arm of the trial but there is no equivalent clustering in the control arm.Several strategies have been proposed for this problem: ignoring the clustering; imposing clusters in the control arm and fitting a fixed or random effects model, or using a partially clustered approach where only the clustering in the treatment arm is modelled.This talk will describe and compare the statistical methods for analysing continuous outcomes from an iRCT with some element of clustering in one arm. Four confirmatory case studies  will be analysed using each of the methods: specialist clinics for the treatment of venous leg ulcers , acupuncture for low back pain , cost-effectiveness of community postnatal support workers (CPSW) , and Putting Life in Years (PLINY) . Recommendations for the best and most practical approaches will be made.


The primary bilateral macronodular adrenal hyperplasia or the independent adrenocorticotropic hormone bilateral nodular adrenal hyperplasia is a rare cause hypercortisolism, its diagnosis is challenging and there is no clear way to decide the best therapeutic approach. Adrenal venous sampling is commonly used to distinguish the source of hormonal production in patients with primary hyperaldosteronism. It could be a useful tool in this context because it might provide information to guide the treatment. We report the case of a patient with ACTH independent Cushing syndrome in whom the use of adrenal venous sampling with some modifications radically modified the treatment and allowed the diagnosis of a macronodular adrenal hyperplasia. Cushing syndrome is a rare disease caused in most cases (after steroid use has been excluded) by a pituitary ACTH-producing adenoma A 76 years-old woman with history of controlled hypertension (with losartan and amlodipine) presented to our hospital referring weight loss of 4 kg in two months, edema that progressed to anasarca and back lumbar pain. Besides the edema her physical examination was completely normal with no clinical signs suggestive of hypercortisolism. Among the studies requested, an abdominal tomography showed a right adrenal gland nodule of 14x9 mm and another one in the left adrenal gland of 23x18 mm , additioWith these results an ACTH (adrenocorticotropic hormone) independent form of hypercortisolism was diagnosed and because the scan of the abdomen had documented the presence of two adenomas, one in each adrenal gland larger than 10 mm, we found ourselves with a therapeutic challenge since the resection of one of the glands may not cure the hypercortisolism in case that the hormonal production came from both glands and the resection of both glands with leave the patient with a permanent hypoadrenalism. It was decided then to perform an adrenal venous sampling to try to determine the origin of the of cortisol production.A previously described protocol was used The patient did not have any postoperative complication and received replacement therapy with hydrocortisone 50 mg every 8 h during the first 48 h and subsequently received prednisolone 10 mg and 0.1 mg of fludrocortisone replacement with resolution of the hypokalemia.The macronodular bilateral adrenal hyperplasia or ACTH-independent macronodular adrenal hyperplasia (AIMAH), is one of the rarest causes of hypercortisolism and its true frequency has not been established. Less than 2% of all cases of hypercortisolism are explained by any form of bilateral adrenal hyperplasia either macro or micro nodular Adrenal vein sampling is used mainly in patients with hyperaldosteronism. Even in high volume centers with experienced radiologist the success rates are around 70 to 90%6. Adrenal vein sampling is rarely used for the study of hypercortisolism and this is probably due to the rarity of cases in which adrenal cortisol secretion and bilateral nodules present together, but it can be a useful test in this group of patients. It is proposed that some patients could be treated with a unilateral adrenalectomy as production of cortisol could be related to the size of the nodule Based on the above it was decided to perform the extraction of both adrenal glands and the result of the pathology confirmed the diagnosis of AIMAH.To our knowledge this is the first report of Adrenal vein sampling in a patient with hypercortisolism and bilateral adrenal adenomas in our country.We made some changes to the procedure reported in the literature, given the difficulty with the measurement of catecholamines we chose to perform verification of proper positioning of the catheter tip by the image from the venography and to correct the dilution difference by measuring aldosterone, the biochemical diagnosis was confirmed histological which allows us to conclude that the verification by venography was adequate.This technique allowed an accurate diagnosis and avoids the need for re-intervention in the case that the glandular size guided the treatment.


With continually increasing global connectivity and wholesale change of landscapes, the need to understand and control the spread of invasive species has never been greater. To do so requires insight into the factors that allow particular species to become invasive to begin with as well as into the evolutionary trajectory those invasive populations follow after establishment in new ranges.One of the more prominent hypotheses explaining the success of invasive species relies on the idea that populations can disperse away from their natural enemies, and thus grow without the constraints of antagonist-mediated control. Recent work by Tiantian Lin et al. builds on this idea by demonstrating parallel evolution of invasive plant populations across three geographically distinct regions towards decreased investment in defense and increased competitive ability. By comparing the competitive ability of native versus invasive genotypes of Common ragwort in either the absence of herbivores or in the presence of either a specialist or a generalist herbivore, the authors were able to show that invasive genotypes outcompete their native conspecifics in both the absence of herbivores and presence of the generalist herbivore, but have lowered defenses against the specialist herbivore  of most founding populations. The authors describe how environmental and genomic perturbations typical of invasion may favor activation of transposable elements, and therefore increase the rate of introduction of potentially beneficial alleles (Stapley et al.


To improve the ability to accurately report CT and MRI by learning to recognise benign findings that may mimic malignant pathology in the setting of scans performed on patients with known malignancy.CT and MR images will be displayed demonstrating benign abnormalities that are easily misinterpreted as metastases, recurrent tumour or residual tumour in patients with known malignancy. Examples of benign findings will be displayed next to the corresponding malignant abnormalities to demonstrate the potential error.The ability to accurately differentiate between benign and malignant disease can be challenging and can contribute to reporting discrepancies even amongst experienced radiologists. This can be especially demanding when imaging patients with known malignancy and is a concern for general and specialist radiologists. Being aware of abnormalities that mimic malignancy will help to increase the accuracy of CT and MR reports and ensure the correct treatment plans are implemented.


Solar radiation is essential for photosynthesis and global crop productivity but it is also variable in space and time, frequently being limiting or in excess of plant requirements depending on season, environment and microclimate. Photoprotective mechanisms at the chloroplast level help to avoid oxidative stress and photoinhibition, which is a light-induced reduction in photosynthetic quantum efficiency often caused by damage to photosystem II. There is convincing evidence that photoinhibition has a large impact on biomass production in crops and this may be especially high in rice, which is typically exposed to high tropical light levels. Thus far there has been little attention to photoinhibition as a target for improvement of crop yield. However, we now have sufficient evidence to examine avenues for alleviation of this particular stress and the physiological and genetic basis for improvement in rice and other crops. Here we examine this evidence and identify new areas for attention. In particular we discuss how photoprotective mechanisms must be optimised at both the molecular and the canopy level in order to coordinate with efficient photosynthetic regulation and realise an increased biomass and yield in rice. As an example, regions such as Central Luzon in the Philippines and Central and East Java in Indonesia can receive accumulative annual solar irradiation of more than 2200 kWh m−2. In regions that are environmentally vulnerable, higher light intensities could result in damage to crops and a significant reduction in yield. Photoinhibition is usually considered as a short-term response to periods of high light although is affected by long-term responses to environmental conditions (acclimation). In order to place photoinhibition in context with agricultural productivity which occurs over longer time scales it would be beneficial to link it with long term weather data. In this short review we summarise the current evidence that high irradiance levels result in significant yield reductions in rice crops at the metabolic and canopy levels.As the only significant source of energy, incident solar radiation (sunlight) at the surface of the earth governs climate and the meteorological cycles and is essential for life. It has a major effect on the diurnal and seasonal temperature variations as well as the productivity of both terrestrial and aquatic plants by providing energy for the assimilation of carbon by plant canopies  within the thylakoid membrane. This creates resonance energy, which is then transferred through neighbouring chlorophyll molecules to photosystems. An excited chlorophyll a molecule can return to ground state after light absorption through several pathways – photochemistry (photosynthesis), thermal dissipation, chlorophyll fluorescence or formation of a reactive oxygen species (ROS). The latter two are much less likely than the former  resulting in a sustained decline in photosynthesis  low light episodes and can substantially limit photosynthesis (Ogren 2 and Pmax (light-saturated photosynthesis) under very high light. While it has been suggested that under certain circumstances it may occur subsequent to photosynthetic down regulation or damage possibly associated with high carbohydrate levels  proteins has been shown to accelerate photoinhibition under strong light  or non-photochemical (occur prior to photolysis in PSII). Non-photochemical quenching (NPQ) refers to the measurement of thermal dissipation of excess excitation energy in PSII  and photoinhibition. In fact, studies show a broad (negative) relationship that exists between the capacity to utilise light energy within photochemical sinks (carbon fixation and growth) and NPQ capacity   difficult. However, the continued development of high-resolution phenotyping platforms (with automated darkening and light treatment) is expected to overcome this and uncover the genetic basis of these traits used in breeding programmes  and less under others (low light or during periods of moderate but rapid high – low transition). The patterns of photoprotection required will be determined by the proportion of canopy surface area exposed to high radiation that induces photoinhibition and the properties of light fluctuations that limit photosynthesis. So how can this problem be solved? Existing models of canopy photoinhibition can predict the impact of ΦCOThe genetic improvement of crop yield will need to be integrative and consider multiple stress and signalling pathways in the plant. In this review we focus on responses to high light, which will compound the effects of other stresses. We have highlighted the weak links between leaf level effects and field yield and explain the case for a better understanding of canopy level optimisation.Finally we note some novel and highly relevant climatic factors related to irradiance. Studies carried out since the 1990s found a decline in solar radiation at the surface of the earth between the 1950s and the 1980s (Wild and Wild


Over a thousand nerve, skin and salivary gland biopsies were performed in FAP patients during the last forty years in our centre. We will try to demonstrate the different biopsy approaches over the years and confirm that biopsy of different types of tissue are useful not just in the diagnosis but also in the study of the pathogenesis of the disease.Retrospective analysis of our database since 1973 till 2014 showed 253 nerve biopsies, 441 skin and 738 salivary gland biopsies. Some of these were combined biopsies, nerve and skin or muscle nerve and skin. Except for the salivary gland biopsies they were all performed by one of our neuropathologists.Until 1988, nerve and skin biopsies were commonly performed for diagnostic purposes, after that with genetic testing being available all tissue biopsies declined in number and were only needed in difficult diagnostic cases or when genetic testing was not available. Nerve biopsy became relevant again with the appearance of atypical clinical presentations or late onset or sporadic patients where the clinical diagnosis of FAP had not been considered. Nerve biopsy was also performed to establish the diagnosis of “de novo” amyloid neuropathy in recipients of domino liver transplants from FAP individuals, who started showing symptoms of neuropathy, and to rule out other causes of neuropathy.Since 2005, salivary gland biopsy has become our method of choice to demonstrate amyloid and is as effective as nerve or skin biopsies.During the last forty years biopsies of different tissues were used to demonstrate amyloid. Nerve biopsy is still a useful tool not just for diagnostic purposes in problematic cases but also to understand the pathogenesis of the disease. Salivary gland biopsy is now our favoured method as it is a minimally invasive procedure and amyloid is demonstrated in very early stages of the disease. Biopsy could also be a tool to monitor treatment with the new drugs available.


Burnout in healthcare workers is deleterious both for the patients as well as for the healthcare workers themselves with consequences ranging from less job satisfaction to increased mortality rates. Burnout in intensivists is reportedly high with almost half of French intensivists having burnout symptoms.The present study was done to estimate incidence and prevalence of burnout in intensivists in the Netherlands and to identify risk factors for burnout.Two online questionnaires were sent: one to all intensivists in the Netherlands and one to the medical directors of Dutch Intensive Care Units (ICUs).A reply was received of 318 out of 664 intensivists (47.9%). Results of 272 intensivists were evaluable, 12 of whom (4.4%) were diagnosed with burnout at the time of the questionnaire. No association was found between working conditions or personal characteristics and burnout, except for the association between burnout and conflict with the hospital management and between burnout and having complaints filed against one. From the medical directors questionnaire it was found that 7.4% of intensivists suffered from burnout in 2013.Incidence and prevalence of burnout among Dutch intensivist was found to be unexpectedly low as compared to the literature. No firm associations were found between burnout and working conditions or personal characteristics. The low incidence and prevalence of burnout in Dutch intensivists might be explained be a lower workload for intensivists as compared to the literature.This study was done with support of the Dutch Society for Intensive Care


This presentation will focus on a UK Cochrane funded project that explored different ways of engaging patients, the public and health practitioners in the development of outcomes for systematic reviews. It is called 'Outcomes Most Important for Patients, Public and Practitioners (OMIPPP)'.http://www.healthtalk.org). Healthtalk researchers reanalysed the original data for clues to outcomes. These were shared, discussed and compared with existing outcomes used in systematic reviews of breastfeeding interventions.Working with three Cochrane Review Groups (CRG); Airways, Ear Nose and Throat (ENT) and Pregnancy and Childbirth we focussed on outcomes for reviews in Asthma, Rhinosinusitis and Breastfeeding respectively. For each group we used a different method to engage; for asthma we facilitated a full day workshop. Working in partnership with Asthma UK, we prepared for this by gathering perspectives of asthma via a Facebook survey, and reviewing existing core outcome sets. Working in partnership with evidENT we gathered perspectives in rhinosinusitis using an online survey and experimented with social media as a way of reaching out beyond their networks as there are no relevant patient groups. We compared survey findings with existing outcomes used for reviews of chronic sinusitis. For breastfeeding we worked with the National Childbirth Trust and the Breastfeeding Network to review an existing online collection of experiences of breastfeeding called Healthtalk (At the time of writing this abstract the project is not yet complete, however early results will be discussed. We are interested in the following aspects of evaluation; how relevant was the gathered data for systematic review outcomes? What were the cost and resource implications of each method? From a review group perspective how feasible are these methods? Has the project extended the reach of CRGs with interested public/patient and practitioner groups? How does our data compare with other outcomes exercises e.g. COMET?


Aspergillus fumigatus, and pre-existing conditions such as pulmonary functional abnormalities such as cystic fibrosis or chronic obstructive pulmonary disease provides a favorable environment for Aspergillus colonization and biofilm formation in the lungs  or during invasive aspergillosis  and are considered as an important virulence determinant for a pathogen. For a fungus specie, growing as multicellular community may confer biological advantages in the colonization of tissues and may also act as barrier to external aggressions  maintenance and stability of biofilms and (ii) biofilm resistance to antifungal drugs. Similar results were also observed for A. fumigatus biofilms, where the treatment with DNAse destabilized biofilm architecture integrity and concomitant treatment of biofilms with DNAse and amphotericin B or caspofungin improved antifungal susceptibility  which consist in masses of decondensed chromatin decorated with antimicrobial proteins and opsonins (McCormick et al., C. albicans (McCormick et al., in vitro models with Aspergillus showed that despite the fact that NETs formation leads to trapping the fungus conferring a fungistatic effect by containing the infection, it does not represent the major factor for killing this fungus since NET-dependent killing of Aspergillus hyphae was only moderated (Bruns et al., in vivo influence of NET's eDNA produced by lungs in Aspergillus biofilm development, which may lead to the combination of antifungal drugs with DNAse to manage pulmonary aspergillosis. Further studies could also explore the Aspergillus ECM physicochemical features and permeability to current antifungal drugs, and these findings may lead to molecular improvement of these drugs by conferring them the capacity to penetrate ECM Aspergillus biofilm and act in their respective molecular targets.Taken together these findings, the next steps would include the elucidation of the 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.