Human brucellosis represents a significant burden to public and veterinary health globally, including the republic of Azerbaijan. The purpose of this study was to examine and describe the spatial and temporal aspects of the epidemiology of human brucellosis in Azerbaijan from 1995 to 2009.I and the Ederer-Myer-Mantel (EMM) test.A Geographic information system (GIS) was used to identify potential changes in the spatial and temporal distribution of human brucellosis in Azerbaijan during the study period. Epidemiological information on the age, gender, date, and location of incident cases were obtained from disease registries housed at the Republican Anti-Plague station in Baku. Cumulative incidences per 100,000 populations were calculated at the district level for three, 5-year periods. Spatial and temporal cluster analyses were performed using the Local Moran’s A total of 7,983 cases of human brucellosis were reported during the 15-year study period. Statistically significant spatial clusters were identified in each of three, five year time periods with cumulative incidence rates ranging from 101.1  to 203.0 . Spatial clustering was predominant in the west early in the study during period 1 and then in the east during periods 2 and 3. The EMM test identified a greater number of statistically significant temporal clusters in period 1 (1995 to 1999).These results suggest that human brucellosis persisted annually in Azerbaijan across the study period. The current situation necessitates the development of appropriate surveillance aimed at improving control and mitigation strategies in order to help alleviate the current burden of disease on the population. Areas of concern identified as clusters by the spatial-temporal statistical analyses can provide a starting point for implementing targeted intervention efforts. Brucella, which primarily infect animal reservoirs. The primary agents of infection in humans are B. abortus (cattle), B. melitensis (sheep and goats), B. suis (swine), and B. canis (dogs) [Brucellosis is a widespread zoonotic disease regarded as an emerging and re-emerging threat to public and veterinary health worldwide . Develops (dogs) . Humans s (dogs) .Clinical signs and symptoms of the disease are usually acute and nonspecific, often mimicking other illnesses . Common The disease was first diagnosed in Azerbaijan in 1922 and quickly established itself, spreading to more than two thirds of the country’s districts in less than thirty years . Recent Despite the current status of human brucellosis in Azerbaijan, there have been no known published efforts to map and describe the occurrence of the disease at a local level. In order to better understand the spatial and temporal distribution of human brucellosis in Azerbaijan, geospatial analytical techniques and a geographic information system (GIS) were employed. Previous studies using spatio-temporal methods to investigate the distribution of health events have been successful in uncovering factors related to the occurrence of disease ,14. ReseThere were three primary objectives of this study: 1) to describe the spatial and temporal distribution of human brucellosis in Azerbaijan; 2) identify the potential presence of clusters of the disease in space and time; and 3) identify epidemiological characteristics of individuals that were diagnosed with an infection.No human subjects work was undertaken in this study, human brucellosis case data were extracted from annual government reports. These government reports are prepared public reports, providing summarized count data of patients diagnosed at government health care facilities by category of disease and year. All data were anonymised.Brucella spp. Suspected cases of human brucellosis are confirmed by laboratory testing with the Rose Bengal, Huddleson, and the Wright serum agglutination tests. Initial laboratory tests are performed at RAPS, with confirmation (through repeat tests) at the Republican APS.Brucellosis is a nationally reportable infectious disease in Azerbaijan. Surveillance and documentation of health events within the country are undertaken by their surveillance and diagnostic laboratory known as the Anti-Plague Station (APS), which is divided into five reporting zones. Each of the five reporting zones has a Regional APS (RAPS) office that responds to health inquiries in order to obtain laboratory samples and verify any diagnosis. In this study a case was defined as any individual with a confirmed positive serology test for http://www.azstat.org/). Yearly case totals and the annual incidence of human cases per 100,000 populations in Azerbaijan were recorded during the 15-year study period . Smoothed risk estimates were calculated from crude cumulative estimates for each time period using the Empirical Bayesian Smoother (EBS) in the GeoDa software package [Cumulative incidences per 100,000 individuals were mapped at the district level for each of the three 5-year time periods to highlight any spatial changes in risk over time. A second administrative level (district) shapefile of Azerbaijan was obtained from the Global Administrative Areas database .where IInformation on the month of diagnosis of the reported cases was examined to identify the presence of a possible seasonality in the reporting of cases. Monthly cases were aggregated into seasons, defined as winter , spring , summer , and fall . Additionally, the Ederer-Myer-Mantel (EMM) test  was implm is the greatest case total for human brucellosis occurring in a district in any of the three time intervals of time series i. Since the statistic is biased to changes in population over time [where ver time ,19, consver time .During the study period 1995 to 2009 there were 7,983 reported cases of human brucellosis in Azerbaijan  cumulative incidence maps indicated the presence of spatial variation in the distribution of risk across Azerbaijan during the three, 5-year time periods Figure . During The LISA cluster analyses identified significantly high-high clusters of human brucellosis cases at the district level during each of the three periods indicating districts of high incidence surrounded by other districts of high incidence Figure . During 2 = 102.3, p<0.001), followed by period 2 (n = 9) , and period 3 (n = 4) . Temporal clusters from period 1 were located predominantly in the Central and Western regions of Azerbaijan while clusters identified during period 2 and 3 were more evenly dispersed across the country; however, there were no statistically significant human brucellosis clusters identified in the Nakhchivan region.There appears to be a distinct seasonality in the temporal distribution of monthly human brucellosis cases Figure . ReportiAge and sex stratified case totals illustrated a disproportionate number of cases reported among males, with males more heavily burdened by the disease across all age groups Figure . There wThis study represents the first attempts to map and describe local (district level) patterns of human brucellosis in Azerbaijan. We used GIS in conjunction with spatial and temporal analytical methods to analyze patterns of cumulative incidence at the district level in Azerbaijan finding evidence of clustering in both space and time. Additionally, our analyzes confirm that human brucellosis persists annually throughout much of the country, particularly the central region. These current analyses affirm the notion that brucellosis has become endemically established since the first documented reporting in the 1920s.The results of this study indicated variation in the spatial and temporal distribution of brucellosis reporting in Azerbaijan. Spatial clusters of cumulative incidence were identified in each time period indicating localized areas of high case reporting with clusters predominant in the west early in the study during period 1 and then in the east during periods 2 and 3. Temporal clustering was higher during period 1, but persisted across periods 2 and 3. The median reporting of cases during the study period exceeded 500 cases annually with approximately 65% of districts reporting at least one case every year during the study period, suggesting the possibility of local (district level) persistence. The number of reported cases most likely represents a significant underestimation of the actual disease burden across the country as human brucellosis is often misdiagnosed or is unreported . AdditioThe temporal distribution of cases showed that there was a greater proportion of brucellosis reporting during period 1(1995 to 1999). Temporal clusters identified by the EMM test also indicated a greater number of significant temporal clusters during period 1, which further corroborated that a larger proportion of cases occurring earlier in the study period. Transformations in the funding and organization of public health management and surveillance during the transitional phase to independence have likely contributed to the elevated reporting of the disease in Azerbaijan during this period . HoweverThe seasonality of brucellosis can often be attributed to the seasonal birthing of small ruminants (goats and sheep) ,25. A reAs brucellosis is not a contagious disease, spatial clusters of human cases are most likely a result of shared food sources, animal processing, more intensive agricultural production zones, or similar socio-cultural practices . ClusterThe gender and age distribution of reported cases indicated a higher burden of disease in males (71.8%) compared to females in all age groups. The disproportionate infection rates in males can possibly attributed to differences in the traditional gender roles of men and women in this region. In Azerbaijan, men tend to take on the responsibility of the handling and slaughter of animals in addition to increased occupational hazards such as sheep herding or working in abattoirs . The repThe gender and age distribution of cases suggests that food-borne illness may not be the predominant means of transmission for the disease in Azerbaijan. While food-borne illness undoubtedly plays a role in the high incidence of the disease, the male dominated patterns of reporting and skewed age distribution point to high levels of occupational exposure related to transmission of the pathogen. Yet, despite the potential occupational burden of the disease efforts also need to be focused on reducing food-borne transmission as previous research has found that the epidemiology of human brucellosis in some areas can potentially shift away from a disease of those who directly handle animals to a food-borne illness . SeveralThe data presented here were taken from historical records that most likely represent an under reporting of the disease. Analyzing cases obtained from government health care facilities may have introduced biased since individuals in more rural areas may not readily have access to care. Additionally, those individuals in a lower socio-economic strata (SES) may not be able to afford care, medication, or travel to government facilities. These populations within rural areas in a low SES are also more likely to participate in an agricultural related occupation, which may thereby have resulted in underreporting of the burden of disease in this study. Since the onset of brucellosis is often insidious the time of diagnosis was used as the date of infection rather than the onset of the disease. Furthermore, cases obtained from healthcare facilities may not be representative of the general population. This may have skewed the monthly reporting of cases since the incubation period can be greater > 1 month and an individual may not immediately seek care . HoweverBrucella species. Spatial analyses were limited to district level reporting and may not reflect localized areas of infection inside of a given district. The age of individuals also could not be tied back to their district of origin and so no adjustments were made. While it was hypothesized that food was not the main source of infection in Azerbaijan there were limited epidemiological data associated with cases in this study and the data do not provide a definitive link to occupational exposure. Furthermore, the dummy regions created to improve the synthesis of reporting for the results do not represent or delineate national recognizable zones.There are also limitations to the sensitivity of serological tests for brucellosis and no data were available on the percentage of human cases that were confirmed on bacterial culture, the gold standard for Recent reporting of brucellosis in Azerbaijan indicates a slight decrease in the incidence of disease, yet without adequate livestock surveillance and veterinary health management the brucellosis situation in Azerbaijan may fluctuate widely. The analyses carried out in this study provide a baseline estimation of the spatial and temporal distribution of brucellosis, thereby allowing for the evaluation of deviations from these trends, which could potentially indicate a health emergency in the population. Additionally, the GIS mapping and statistical methodologies may provide a first step in identifying potential problem areas associated with high disease levels. These data can inform policy for implementing appropriate surveillance and control measures. In Azerbaijan where a majority of cases appear to be male dominated as a result of occupational exposures implementing targeted livestock vaccination strategies would seem to be the most prudent choice for control. Districts identified as having high rates of the disease could be initially targeted for directed public health interventions. Future public health management efforts and research in this region should focus on incorporating data on livestock in conjunction with human data to better understand the transmission dynamics of brucellosis.The authors declare that they have no competing interests.ITK and JKB designed the experiments. RA, RI, NU, AT, ITK constructed the historical GIS data sets. ITK, JKB, RA performed the spatial analysis. ITK performed the spatio-temporal analysis. ITK, JKB, RA, RI drafted the manuscript. All authors read the final draft of the manuscript. RA and ITK contributed equally to this work. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/12/185/prepub


Risk models are widely used to predict outcomes after cardiac surgery. Not only is risk modelling applied in the assessment of the relative impact of specific risk factors on surgical outcomes, but also in patient counselling, the selection of treatment options, comparison of postoperative results, and quality-improvement programmes. At least 19 risk-stratification models exist for open-heart surgery. The focus of risk models was originally on pre-operative prediction of mortality. However, major morbidity is in general more common than mortality and the ability to predict only operative mortality is not an adequate method of determining surgical outcome. Multiple intra- and postoperative variables have been excluded in the majority of models and the possible effect of their future inclusion remains to be seen. The unique patient population of sub-Saharan Africa requires a unique risk model that reflects the patient population and levels of care. Risk models are widely applied in the assessment of the relative impact of specific risk factors on surgical outcomes. These models enable surgeons to select the ideal treatment option for a specific patient and to counsel patients accordingly. They allow for comparison of postoperative results and assist in assessment of quality-improvement programmes.2One of the original aims for the development of cardiac risk models was risk adjustment, allowing fair comparison of treatment outcomes among different institutions or surgeons.3The first widely used risk model, the Parsonnet score, was based on a retrospective analysis of data collected during the 1980s.5At least 19 risk-stratification models exist for open-heart surgery.Table 1.The focus of risk models was originally on pre-operative prediction of mortality. However, major morbidity is in general more common than mortality, and the ability to predict only operative mortality is not an adequate method of determining surgical outcome.1The assessment of variables that may affect patient outcome, which are not necessarily related to pre-operative patient characteristics, are also often not taken into account. These variables include factors related to the skill and experience of the surgical and postoperative care teams, which in turn influence various aspects of the intra-operative and immediate postoperative period.7Cardiac risk models are generally comparable with regard to the pre-operative risk factors included. The most widely used models (e.g. EuroSCORE) were usually designed for various cardiac surgical procedures and cannot necessarily account for co-morbid diseases and aspects of the underlying pathophysiology/disease progression not included in the calculation of risk.8The objective of this article is to provide a review of the most common currently used risk-stratification models in cardiac surgery, with critique in general that relates to practice in sub-Saharan Africa.There are a number of risk-stratification models in cardiac surgery. Three of the most widely used models, applicable to multiple cardiac procedures, include the European System for Cardiac Operative Risk Evaluation (EuroSCORE), the Society of Thoracic Surgeons (STS) algorithms, and the Parsonnet score.1 These will be briefly discussed.Combining the most important pre-operative risk factors, the EuroSCORE method has been shown to be a valuable measure for prediction of immediate death after adult cardiac surgery.1The clinical aim of the logistic EuroSCORE was to construct a scoring system predicting early mortality in cardiac surgical patients in Europe on the basis of objective risk factors.10The EuroSCORE provides two methods for calculating predicted outcome: the additive model and the logistic model.14Although well established and validated in patient populations, the additive EuroSCORE sometimes underestimates the risk when certain combinations of risk factors co-exist.Evidence that the EuroSCORE might be out of date led to the collection of new data to enable re-evaluation. Data collection started early in 2010. It was estimated that if enough centres participated, data collection would only take three weeks, but the longest period asked for would be three months.18The Society of Thoracic Surgeons National Cardiac Database (STS NCD) was created in 1989 and it has become the largest clinical database of its kind. The primary aim for the development of the STS model was the support of national quality-improvement programmes. Now it is also used for research focusing on improvement of patient care and outcome.19The STS NCD is unparalleled in terms of its size and comprehensiveness: data were collected prospectively from more than 950 participating centres in the United States.20STS risk models for various cardiac procedures have been developed since 1999 and have undergone periodic revisions.21The predictive performance of the STS algorithms is in general comparable with other systems and remains the most widely used model in the United States.The Parsonnet score was first described in 1989 by Victor Parsonnet. The aim was to construct a straightforward uniform reporting system for levels of operative mortality risk in all cardiac surgical procedures, which included data that are readily available. It includes objective risk factors in order to leave little room for bias.3Development took place in the United States and included data from 3 500 patients collected between 1982 and 1987. Retrospectively, analyses included uni- and multivariate logistic regression models. The model was prospectively tested in an additional 1 332 procedures at a single site. A second, additive model was also developed. This method was tested at two other centres and the outcomes were comparable to those of the hospitals.3The Parsonnet score received widespread acceptance, but the predictive accuracy has been diminished as a result of advances in treatment.In recent years, several models have predicted a rising probability of operative mortality while the observed mortality has decreased.24It is furthermore believed that risk models usually predict outcome more accurately in the setting where it was originally developed.Risk models have diverse clinical aims. The choice of inclusion/exclusion of risk factors as well as the number of risk factors included in the model is influenced by the clinical aim.8Risk factors associated with outcomes generally are likely to reflect concurrent, disease-specific variables whereas factors associated with increased resource utilisation reflect serious co-morbid disease.27Models are sometimes criticised for multicollinearity. Intercorrelations between independent variables included in risk models are known as multicollinearity (e.g. obesity and diabetes mellitus). Including large numbers of independent variables increases the risk of multicollinearity and the consequent inclusion of redundant information in the model.8Excessively complex models with too many variables will appear to have an extremely good fit in the training set, but generalise poorly to test samples and have limited predictive abilities. This is known as overfitting.8Different operators will provide different interpretations to categorical risk factors, such as chronic obstructive pulmonary disease and unstable angina. Even with clearly stated definitions, a degree of personal interpretation takes place, resulting in different final risk scores.18Some models have been criticised for not being able to predict individual risk. Currently utilised models are derived from the studies of very large populations and although very effective at predicting population outcomes, are not necessarily suited for the prediction of risk of an individual patient.Most of the scores are unsuitable for individual risk prediction despite the sample size. This is due to a simple methodological reason: the application of logistic regression models mathematically describes a multiphasic, more complex behaviour of a survival curve that cannot achieve enough statistical power to achieve enough statistical accuracy for individual predictions.27Lastly, the focus of cardiac risk models was originally on pre-operative prediction of mortality, but complications and potentially preventable morbidity are also important outcomes.3Open-heart surgery is one of the most expensive surgical procedures in a hospital. The cost of surgery can vary enormously between patients with an uncomplicated recovery and those who suffer from postoperative complications.28Risk stratification is not only essential for improvement of surgical outcomes, but also allows quality analysis and meaningful comparison of outcomes. Kolh (2006) stated that it should be an integral part of cardiac surgical practice, and quoted ‘... being as essential to the surgeon as the knowledge of anatomy and techniques’.Clinical research and treatment strategies of cardiovascular disease as well as risk-prediction models have largely been developed in North America and Europe. However, the applicability of results derived from these investigations is unknown.12Even though the mortality outcome predicted with the EuroSCORE seems applicable in South African practice, different stages of epidemiological transition are often at work in South Africa and changing patterns in the development of cardiovascular disease are observed in the various ethnic populations.As a result, cardiac surgeons in South Africa face three options with regard to risk stratification: to simply use external risk scores, knowing that the identified risks and attributed weights might not correctly reflect their patient population; to adjust the weight of the risk factors on the basis of their own data; or to derive a new internal model from their own data and recalibrate it periodically.25Variables that may affect patient outcome but which are not necessarily related to pre-operative patient characteristics, are often not taken into account. These include the skill and experience of the surgical and postoperative care team, which influences various aspects of the intra-operative and immediate postoperative period.It is our hypothesis that the development of an integrated model that includes hitherto unutilised intra-operative risk factors as well as other known peri-operative risk factors predictive of outcome should enable more accurate risk stratification and consequently improved quality management of surgical treatment of patients with cardiovascular disease in the South African setting. Such a model would allow for improved clinical decision making, assessment of surgical performance and quality of care. Increasing efficiency through prediction of postoperative complications would ultimately facilitate decisions to operate, allocate resources and estimate costs.28


Eucalyptus tree species and hybrids make them excellent renewable sources of fiber for pulp and paper production, and woody biomass for bioenergy production. Our research is aimed at understanding the genetic regulation of wood formation in eucalypts, with a focus on transcriptomes, regulatory sequences and gene families involved in secondary cell wall biosynthesis.The fast growth and good wood properties of Eucalyptus grandis trees with the aim to investigate the transcriptional control of cellulose biosynthesis and wood formation. The transcriptome datasets range from nearly mature xylogenic tissues to immature shoot tips, and consists on average 35 million paired-end 80bp short reads. The Illumina short reads were mapped to the latest Eucalyptus grandis genome sequence , and the set of predicted gene models provided by the Joint Genome Institute (JGI). We calculated tissue specific gene expression (FPKM) profiles for each of the ~44 000 predicted genes across the sequenced transcriptome datasets. The results were stored in a relational database for further analysis and analysis of co-expression patterns in the expression profiles. We ultimately aim to identify genes that are differentially expressed and co-regulated during different stages of wood formation.We have performed deep mRNA sequencing (using Illumina RNA-Seq technology) of several primary and secondary tissues of three Eucalyptus Genome Explorer (EucGenIE), modeled after the poplar resource, PopGenIE . EucGenIE relies on a relational database system that allows for the efficient storage and retrieval of gene models and expression values from the database, which is then presented to the user in novel and intuitive ways. The web-based front-end makes use of tools available in the Generic Model Organism Database  toolkit to enrich the query interface as well as result visualization. Links to the Phytozome GBrowse instance provides genomic context to the expressed gene sets. Custom queries allows the user to find genes with similar gene expression profiles across the various datasets, as well as perform bulk searches on sequence features annotated on the gene set. EucGenIE also provides access to common analyses tools, such as homology searching and online clustering tools. The first version of the EucGenIE database and online portal is available at http://eucgenie.bi.up.ac.za with restricted access.We describe the initial development of an Integrative


Generalized tonic-clonic seizures (GTCS) are characterized by unresponsiveness and convulsions, which cause complete loss of consciousness. Many recent studies have found that the ictal alterations in brain activity of the GTCS epilepsy patients are focally involved in some brain regions, including thalamus, upper brainstem, medial prefrontal cortex, posterior midbrain regions, and lateral parietal cortex. Notably, many of these affected brain regions are the same and overlap considerably with the components of the so-called default mode network (DMN). Here, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients are different from normal controls, even in the resting state. To test this hypothesis, we compared the DMN of the GTCS epilepsy patients and the controls using the resting state functional magnetic resonance imaging. Thirteen brain areas in the DMN were extracted, and a complete undirected weighted graph was used to model the DMN for each participant. When directly comparing the edges of the graph, we found significant decreased functional connectivities within the DMN of the GTCS epilepsy patients comparing to the controls. As for the nodes of the graph, we found that the degree of some brain areas within the DMN was significantly reduced in the GTCS epilepsy patients, including the anterior medial prefrontal cortex, the bilateral superior frontal cortex, and the posterior cingulate cortex. Then we investigated into possible mechanisms of how GTCS epilepsy could cause the reduction of the functional integrations of DMN. We suggested the damaged functional integrations of the DMN in the GTCS epilepsy patients even during the resting state, which could help to understand the neural correlations of the impaired consciousness of GTCS epilepsy patients. A consistent network of human brain regions, including medial prefrontal cortex, posterior midbrain regions, medial temporal lobes and lateral parietal cortex, showed high levels of activity when no explicit task was performed Though notoriously difficult to define, consciousness is central to many neurological conditions, ranging from neurodegenerative dementias to coma and vegetative states, and from sleep disorders to epilepsy Functional connectivity (FC), which studies temporal correlations between the signals in different brain regions, has been widely used in functional magnetic resonance imaging (fMRI) studies to investigate direct or indirect interactions between brain regions In the present study, we hypothesize that the brain activity of the DMN of the GTCS epilepsy patients may be different from one of the normal controls, even in the resting state. To test this hypothesis, using the graph theory, we compared the DMN of the GTCS epilepsy patients and the controls with the resting state fMRI data.The study involved 14 GTCS epilepsy patients and 29 healthy normal subjects. All participants were male and right-handed. Fourteen epilepsy patients were recruited from the department of neurosurgery of Southwest Hospital of the Third Military Medical University, and 29 controls were recruited by advertisement. There was no significant difference in age between the two groups . All participants gave written informed consent. This study was approved by the ethical committee of the Third Military Medical University.The clinical information of the GTCS epilepsy patients, including The National Hospital Seizure Severity Scale (NHS3), was collected through interviews with the patients and their relatives who had witnessed the patient's epileptic seizures. Any abnormity had not been detected for all of the patients in routine MRI examinations. None of the patients reported a history of drug intoxication, encephalopathy, or brain trauma. However, an experienced EEG physician found that all the patients showed generalized spike and wave or polyspikes discharges against a normal background in Video-EEG monitoring. Based on their seizure history, their seizure semiology and results from video-EEG recording, these patients were diagnosed as idiopathic generalized epilepsy (IGE) with only generalized tonic-clonic seizures according to the International League Against Epilepsy (ILAE) classification. More information about the patients was shown in Twenty-nine controls underwent a comprehensive MRI brain examination to ensure that they had no neurological lesions. All controls had no history of neurological or systemic illness, head injury, and drug or alcohol abuse.MR imaging was carried out using a 3.0-Tesla MR scanner . Functional images were collected axially by using an echo-planar imaging (EPI) sequence sensitive to BOLD contrast. The acquisition parameters were as follows: 36 slices, 2000/30 ms (TR/TE), 3.0/1.0 mm (thickness/gap), 192Additionally, anatomical image datasets were also acquired with a standard T1-weighted high-resolution anatomic scan of a magnetization-prepared rapid gradient echo (MPRAGE) sequence for each participant in this study.http://www.fil.ion.ucl.ac.uk/spm). The first 10 volumes of each participant were discarded. The remaining 230 functional scans were first corrected for within-scan acquisition time differences between slices and realigned to the first volume to correct for inter-scan movements. Next, the functional scans were spatially normalized to a standard EPI template and resampled to the voxel size of 3http://afni.nimh.nih.gov/). The parameters obtained during movement correction showed that the maximum displacement in the cardinal direction was not greater than 1 mm, and the maximum spin was not greater than 1° for each participant.Image preprocessing was conducted using SPM2 . The mean DMN graphs respectively for the two groups were shown in Comparing the strength of the functional connectivity within the DMN between the two groups, we found significantly decreased functional connectivity in the GTCS epilepsy patients group , as shown in Additionally, we found that the strength of the functional connectivity between the aMPFC and the ventral anterior cingulate cortex (vACC) was significantly correlated to the NHS3 score of the GTCS epilepsy patients .As mentioned in the introduction, many studies have found that the brain activities of some brain areas in DMN are abnormal for the GTCS epilepsy patients, whereas most of these studies focused on the ictal alterations in brain activity. The present study used the resting state fMRI and the graph theory to investigate the functional integrations of DMN for GTCS epilepsy patients. We found significantly decreased functional connectivity within the DMN of the GTCS epilepsy patients in comparison to the controls. Additionally, the degree of some brain areas within the DMN was significantly reduced. Taken together, these results suggest the reduced functional integrations of the DMN in the GTCS epilepsy patients, even in resting state.Single-photon emission computed tomography (SPECT) studies found that cerebral blood flow (CBF) decreases occurred during and following secondarily generalized tonic-clonic seizures in the medial prefrontal cortex, posterior cingulate gyrus and lateral parietal cortex, overlapping the core elements of the DMN. Concurrently, analysis of patient behavior showed impaired consciousness during and following seizures Here, we think that there are the following possibilities to cause the reduction of functional integrations of the DMN in the GTCS epilepsy patients.More and more evidence show that the “resting state” may be much more than a “noise background”, and it is likely to reflect a default or intrinsic functioning mode of human brain It is possible that the interictal discharges, which appears frequently during the resting state fMRI scanning, would reduce functional integrations of the DMN. The recent EEG-fMRI simultaneous recording studies found, when the generalized spike wave appeared, the posterior cingulated gyrus, precuneus, and the lateral parietal cortex showed a negative activation, whereas the medial frontal cortex showed incomplete synchronized activities The epilepsy patients in the present study take some antiepileptic medications, most of which are the first generation of antiepileptic drugs and derived from sedatives. These drugs can cause some side effect on physiological processes, including neurotransmission and metabolism, and further damage the cognitive ability Chronic epilepsy generally impairs cognition, but it can also cause functional reorganization and plasticity Summarily, we prefer to think that the four mechanisms might act together to cause the reduction of the functional integrations of the DMN in the GTCS epilepsy patients. In future, we plan to use EEG-fMRI simultaneous recording technology to classify the resting state fMRI scanning according to whether the epileptiform waves exist or not. Thus, we can identify whether the reduced functional integrations of the DMN in the GTCS epilepsy patients would result from the impaired intrinsic brain activity or the incomplete synchronized brain activities during the epilepsy activity. Additionally, there is no wide agreement of the composition of the DMN, and we used a priori regions of interest to define the DMN in the present study. A complete undirected weighted graph with 13 nodes gives an approximate picture to the DMN. As the study of the DMN goes in depth, we believe that there will be more appropriate methods for modeling the DMN.In this study, we found significantly decreased functional connectivity within the DMN of the GTCS epilepsy patients in comparison to the controls. Additionally the degree of some brain areas within the DMN was significantly reduced. It is possible that several mechanisms might explain these findings. However, these results suggest the reduced functional integrations of the DMN in the GTCS epilepsy patients, which could be helpful to understand the neural correlation of the impaired consciousness of GTCS epilepsy patients.


Selar crumenophthalmus) in the presence of an anchored floating object, constituting a point of attraction for several fish species. We constructed a field-based model for aggregated-fish dynamics, deriving effective interactions for both social and external stimuli from experiments. We tuned the model parameters that best fit the experimental data and quantified the importance of social interactions in the aggregation, providing an explanation for the spatial structure of fish aggregations found around floating objects. Our results can be generalized to other gregarious species and contexts as long as it is possible to observe the fine-scale movements of a subset of individuals.Demonstrating and quantifying the respective roles of social interactions and external stimuli governing fish dynamics is key to understanding fish spatial distribution. If seminal studies have contributed to our understanding of fish spatial organization in schools, little experimental information is available on fish in their natural environment, where aggregations often occur in the presence of spatial heterogeneities. Here, we applied novel modeling approaches coupled to accurate acoustic tracking for studying the dynamics of a group of gregarious fish in a heterogeneous environment. To this purpose, we acoustically tracked with submeter resolution the positions of twelve small pelagic fish ( Despite the social and economic importance of fisheries, quantitative tools capable of predicting fish distribution and its variations with respect to environmental changes and human activities are still missing. The main approaches that are currently used in fisheries management require going beyond the study of isolated target fish species and demand taking into account intra- and inter-specific interactions, behavioral factors as well as responses to the environment Selar crumenophthalmus, in the proximity of a FAD located in Saint Paul's Bay at Reunion Island (West Indian Ocean) In this paper, we introduced a new modeling approach, coupled to accurate acoustic tracking measurements, capable of quantifying the driving forces leading to aggregation. We considered an obligate schooling small pelagic fish species, radial distributionpair-correlation functionTwo variables were considered to characterize the individual fish dynamics: turning angle and swimming speed in the  at zero . At the ro  validating a certificate of training in animal experimentation and a degree in experimental surgery on fish.The experiment was conducted in open field of a shallow-water region (17 m depth in average) in the center of Saint Paul's Bay in Reunion Island (South Western Indian Ocean). The HTI™ Acoustic Tag Tracking System (Model 290) was composed of five hydrophones connected by cables to the Acoustic Tag Receivers system embedded on the boat. These hydrophones surrounded the boat in a square of approximately 100 meters per side . It is a small coastal pelagic fish common in the circumtropical area The fish species we studied was the big-eye scad Click here for additional data file.Figure S2Trajectories of the tracked fish in the (TIF)Click here for additional data file.Figure S3Current speed (red line) in cm/s and current angle (blue line), with respect to the North  recorded during the experiment.(TIF)Click here for additional data file.Figure S4Swimming speed distribution (A), turning angle distribution (B) and pair-correlation function (C), calculated at different radial distances from the FAD.(TIF)Click here for additional data file.


Anomalous origin of left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital anomaly that causes a left-to-right shunt via the coronary system, resulting in coronary steal. We report an unusual case of a healthy 48 years-old patient presenting with dyspnea on exertion and mild chest pain who underwent surgical correction of this rare anomaly. Multiple procedures have been proposed in adults with ALCAPA. Although re-implantation of the left main coronary artery (LMCA) to the aorta remains the most physiological correction for this anomaly, the combination of LMCA ligation and coronary artery bypass grafting provides a dual coronary flow system and is preferable when re-implantation is impossible. Anomalous origin of left coronary artery from the pulmonary artery (ALCAPA) is an uncommon congenital anomaly affecting 1/300,000 live births [We present herein an unusual case of ALCAPA seen in one of the oldest patient ever reported.An otherwise healthy 44-year-old man presented with dyspnea on exertion and slight chest pain in 2007. Coronary angiography led to the diagnosis of ALCAPA, with a nuclear stress imaging test positive for ischemia. He initially refused surgery because the symptoms were well tolerated. Four years later, at the age of 48, the patient experienced aggravating dyspnea on exertion. Pre-operative coronary angiography showed no other anomaly than the ALCAPA. Left ventricular ejection fraction was normal on echocardiography. Cardiac computed tomography angiography (CTA) with 3D reconstruction Figure  demonstrIn order to provide dual coronary perfusion, we proceeded with on-pump beating-heart coronary artery bypass grafting (CABG) of the left anterior descending coronary using a large saphenous vein graft (SVG) harvested in the proximal calf, selected to match the size and the significant flow in the LAD Figure . Using tThis exceptional case of a late presentation of ALCAPA was not only interesting from a clinical and imaging perspective but also from a therapeutic standpoint. Since patients with this anomaly rarely survive past infancy without surgical correction, very few adult patients have been reported in the literature, especially after 40 years old. We believe that patients can survive through adulthood with this anomaly without significant myocardial damage because of the development of an important collateral flow from the RCA.Multiple procedures have been proposed in adults with ALCAPA including ligation of the left main coronary artery (LMCA), re-implantation of the LMCA to the aorta, creation of a baffle through the pulmonary artery (Takeuchi procedure) and a combination of LMCA ligation and CABG. Although re-implantation of the LMCA to the aorta remains the most physiological correction for this anomaly, the combination of LMCA ligation and CABG provides a dual coronary flow system and is preferable when re-implantation is impossible ,3.In this case, re-implantation of the LMCA into the aorta was considered unfeasible because of the distance between the insertion site of the LMCA on the PA and the aorta. The Takeuchi procedure was also considered but discarded because of the reported increased risk of supra-valvular stenosis as the distance increases between the insertion site of the LMCA and the junction between the aorta and the pulmonary artery . End-to-The collateral flow in this patient was impressive. Following LMCA ligation on CPB, cardiac arrest was not attained despite adequate cool antegrade and retrograde cardioplegia flow and relative hypothermia. In order to match the size of the large LAD, allow unrestricted flow and avoid competitive flow between the graft and the collaterals from the RCA, the largest possible conduit was selected. The choice of a large SVG conduit over an arterial graft  was in response to this situation.In a series of 6 adult patients who underwent saphenous vein bypass grafting and direct ALCAPA closure from inside the PA, Moodie and associates reported a graft patency rate of 80% at a mean follow-up of 5.8 years . MoreoveWritten informed consent was obtained from the patient for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.ALCAPA: Anomalous origin of left coronary artery from the pulmonary artery; CABG: Coronary artery bypass graft; CTA: Cardiac computed tomography angiography; LMCA: Left main coronary artery; PA: Pulmonary artery; RCA: Right coronary artery.The author(s) declare that they have no competing interests.POD: Has made substantial contributions to conception and design and has been involved in drafting the manuscript. NP: Has been involved in drafting the manuscript and revising it critically for important intellectual content. JF: Has made substantial contributions to conception. LMS: Has revised the article critically for important intellectual content. CC-L: Has made substantial contributions to analysis and interpretation of data. SM: Has made substantial contributions to conception. NN: Has performed the surgery, revised the article critically for important intellectual content, is the corresponding author. All authors read and approved the final manuscript.Video 1.mov. Intra-operative video showing the increase in size of the tortuous coronaries on the beating heart.Click here for file


The complete surgical removal of disease is a desirable outcome particularly in oncology. Unfortunately much disease is microscopic and difficult to detect causing a liability to recurrence and worsened overall prognosis with attendant costs in terms of morbidity and mortality. It is hoped that by advances in optical diagnostic technology we could better define our surgical margin and so increase the rate of truly negative margins on the one hand and on the other hand to take out only the necessary amount of tissue and leave more unaffected non-diseased areas so preserving function of vital structures. The task has not been easy but progress is being made as exemplified by the presentations at the 2nd Scientific Meeting of the Head and Neck Optical Diagnostics Society (HNODS) in San Francisco in January 2010. We review the salient advances in the field and propose further directions of investigation. Optical technologies are being used not only to detect disease but also direct treatment (laser) and activate photodynamic therapy as well as in cases aid in the activation of nano-devices to deliver a therapeutic effect. We briefly outline some of the excellent evidence presented in the 2nd Scientific Meeting of the Head and Neck Optical Diagnostics Society (HNODS), Figure  in San FOptical diagnostics have proved to be a reliable resource that can be used to provide an instant diagnosis of soft and, more recently, hard tissue diseases. In the field of head and neck malignancy, most of the experimental spectroscopy work has been performed using fluorescence spectroscopy, Raman spectroscopy, elastic scattering spectroscopy, micro-endoscopy and optical coherence tomography. These have all shown a marked increase in the sensitivity and specificity when compared to both clinical examination and frozen section analysis .in situ optical signature. Most of these techniques have been applied only in clinical trials and are yet to be employed in clinical practice, with the exception of fluorescence spectroscopy. Results from these trials are very promising and current results indicate the possibility of these techniques being applied in clinical practice in the next few years. This could have a great impact on diagnostics, by reducing the histopathology workload, reducing patient's anxiety, and allowing rapid surgical or adjuvant intervention [Optical biopsies can be acquired through different modalities; each has it own mechanism of action and requires different modes of data analysis. However, they share the ability of being able to provide a real time, non-invasive and rvention . Furtherrvention .Visualizing the respiratory mucosa in pulmonary airways at the sub-cellular level could yield new insights into pathogenesis of many important diseases. However, current imaging modalities to study the respiratory mucosa lack the required resolution to visualize critical sub-cellular detail such as nuclei and respiratory epithelial cilia .in situ with high spatial resolution in all three dimensions. Liu et al. have developed a FFOCM with an axial sectioning thickness of 1 μm and a high transverse resolution of 0.6 μm. Individual epithelial cells and goblet cells, including their sub-cellular morphologies, were seen. Their results demonstrated the potential of FFOCM to provide detailed micro-structural imaging of pulmonary airways without administration of a contrast medium [Full-field optical coherence microscopy (FFOCM) is an emerging technique capable of providing reflectance images t medium .in vivo is crucial for understanding the normal and diseased lung. In particular, understanding the three-dimensional geometry and relationship of the terminal alveoli to their neighboring alveoli, alveolar ducts and acini during respiration would be a major advance. However, the lung is an inherently difficult organ to image in vivo and the peripheral lung has many compounding challenges not limited to its highly scattering micro architecture, large motion artifacts and difficult access through the bronchial tree. Namati et al. used a high-speed high-resolution optical frequency domain imaging (OFDI) system that is endoscopically compatible for future in vivo imaging of human alveoli. They showed that OFDI images reveal clear delineation of alveolar septal walls, demonstrating that high-speed three-dimensional visualization of air filled alveoli is feasible [Investigating the structure and function of pulmonary alveoli feasible .Lung disease involving the alveoli and distal bronchioles are poorly understood and most commonly studied indirectly via lung function tests. Unglert et al. showed that alveolar microstructure could be resolved in three dimensions in images obtained by intra-vital fluorescence microscopy and optical coherence tomography .Furthermore, lung cancer is the leading cause of cancer-related death, and despite recent efforts to reduce the mortality associated with the disease, patient prognosis remains poor with the current 5-year survival rate under 15%. Detection and diagnosis of lesions arising in the bronchial mucosa remains problematic and as a result they are typically well advanced upon discovery.Suter et al. described their experience in using optical frequency domain imaging (OFDI) to interrogate the bronchial mucosa of patients with the suspicion of lung cancer. During bronchoscopic evaluation, regions of interest suspicious of cancer or precursor lesions were identified and imaged, in addition to regions of normal appearing mucosa. OFDI imaging of the pulmonary airways may enable the early detection of airway features associated with the development of cancer. When used as a screening tool in high-risk patients, it is hoped that early detection of airway-associated cancer with OFDI will result in a decrease in patients' mortality .in vivo, time-domain OCT. They found that down to a depth of 1.5 mm, micro-anatomical structures were clearly identifiable on the OCT images. OCT reached a sensitivity of 100% and a specificity of 92% or 75% , respectively. This method seems highly promising for early, non-invasive tumour diagnosis in the UADT [Non-invasive differentiation of pre- and early malignant mucosal changes may be helpful to reduce the morbidity and shorten the time to diagnosis for the patients concerned. Optical Coherence Tomography (OCT) seems to be well suited to reach this goal. Volgger et al. reviewed 82 primary leukoplakic or erythroplakic mucosal lesions of the upper aero-digestive tract (UADT) prospectively using an ex vivo Swept-Source Frequency-Domain OCT. They suggested that the use of OCT in clinical examination and monitoring can be invaluable tool for inexperienced clinicians [Optical biopsy systems have been investigated for various clinical applications; however the main interest remains in the diagnosis and monitoring of premalignant and malignant conditions. Hamdoon et al. acquired suspicious oral lesions from 120 patients which were then subjected to immediate inicians . Opticalinicians .Rubinstein et al. found that the OCT system is non-invasive and easy to incorporate into the operating room as well as to the outpatient clinic. It requires minimal set-up and requires only one person to operate the system. OCT has the distinctive capability to obtain high-resolution images, where the microanatomy of different sites can be observed. OCT technology has the potential to offer a quick, efficient and reliable imaging method to help the surgeon not only in the operating room but also in the clinical setting to guide surgical biopsies and aid in the decision making of different head and neck pathologies .in situ. This system is essentially a wide-field epi-fluorescence microscope coupled to a 1 mm in diameter flexible fiber-optic imaging bundle capable of imaging nuclear size and nuclear-to-cytoplasmic ratio following topical application of a fluorescent labeling solution [For oral cancer, biopsy has a low specificity because of a thick keratin layer that often covers potential malignancies. Sterenborg et al. investigated the possibility to distinguishing potentially malignant visible lesions from benign ones using differential pathlength spectroscopy (DPS) to reduce the number of unnecessary biopsies in 75 suspicious lesions and 35 clinically normal locations that were not biopsied. They showed that the area under the ROC curve was 0.951 . Pierce solution .The development of lymphadenopathy in the neck has many causes, in children it is often found in relation to infection and in a small but significant number it is the first presentation of lymphoma. In adults neoplastic causes predominate for example, lymphoma, squamous cell carcinoma and adenocarcinoma. The treatment modalities and prognosis for these conditions varies enormously and in the case of squamous cell carcinoma, an excision biopsy can lead to significant morbidity. Orr et al. investigated the ability of Raman spectroscopy to differentiate between the major neoplastic diseases of lymph nodes presenting within the neck. Pre-treatment accurate diagnosis is imperative and is a compelling argument for investment in the development of accurate, sensitive and minimally invasive diagnostic techniques, such as Raman spectroscopy .in situ. Elastic light-scattering spectroscopy (ESS) is a point spectroscopic measurement technique, which is sensitive to cellular and sub-cellular morphological features. Normal and abnormal tissues can generate different spectral signatures as a result of changes in nuclear size, density, and other sub-cellular features, the optical-spectroscopy equivalent of histopathological readings. ESS is optimal for use in the small-volume area as found in thyroid FNA. An important advantage of ESS is that it provides an objective and quantitative assessment of tissue pathology that may not require on-site special expertise and subjective image interpretation as in conventional histopathology. Rosen et al. described their experience in the clinical application of elastic scattering spectroscopy in the thyroid [Thyroid cancer is the most common endocrine malignancy. The standard of care in the management of a patient with a thyroid nodule is fine-needle aspiration (FNA) biopsy with cytological evaluation. While 5-10% of nodules are malignant, 10-25% of FNAs' are indeterminate. Consequently, about twice as many patients undergo surgery for a suspicious lesion that turns out to be benign to patients undergo surgery for a known malignant lesion. A more accurate molecular and ultra-structural based algorithm would be useful to improve diagnostic accuracy. Non-invasive optical tissue diagnosis mediated by fiber-optic probes can be used to perform non-invasive, or minimally-invasive, real-time assessment of tissue pathology  thyroid .Within the discipline of Otology, Just et al. used OCT images and 3D reconstructions demonstrate the usefulness of OCT to measure the drilling cavity, to visualize the inner ear structures, and to obtain micro-anatomical information about the round and oval window niche. They suggested that OCT-guided drilling allows identification of the intact inner ear more precisely . OpticalVisible light is a source of energy known to activate the visual system through absorption by photoreceptors in the eye. When the "stress-confinement" condition is fulfilled, laser light can induce an acoustic signal through an opto-acoustic effect. Wenzel et al. sought to assess if visible light with parameters that induce an optoacoustic effect  could be used to stimulate the peripheral hearing organ at ear drum and middle ear level. The group demonstrated that visible light can be used to activate the peripheral hearing organ when applied at the ear drum level or on bony structures within the middle ear that can transmit vibrations to the cochlea or inner ear. They suggested that the technique could be used to improve implantable and non-implantable hearing .Wisweh et al. showed that automated classification of laryngeal lesions using optical coherence tomography data can be helpful in making a faster and safer diagnosis. A change in the epithelial layer thickness seems to be an effective indicator for laryngeal cancer and its precursors .Within the discipline of dentistry, Choo-Smith et al. are developing a combined optical coherence tomography (OCT) and polarized Raman spectroscopy (PRS) system for the detection of early non-cavitated dental caries. OCT provides high resolution morphological depth imaging of incipient caries. In combination, OCT and PRS have potential for detecting and monitoring early lesions with high sensitivity and high specificity .Optical technologies improve a clinician's ability to discriminate between normal and diseased tissue. This has obvious advantages including automation, objectivity and reproducibility to give consistent results with defined accuracies.In the treatment of cancer, the fundamental surgical goal is to remove all local malignant disease and leave no residual malignant cells. Studies have demonstrated the benefit of achieving negative resection margins in terms of disease free local recurrence and overall survival. The surgical margins for head & neck cancer may vary widely depending on the site of disease. Assessment of tumour resection margins using optical coherence tomography was performed by Hamdoon et al. in 25 patients with early stage oral squamous cell carcinoma (OSCC) who underwent local resection. The group found that the junctional epithelium (between positive and negative margins) can be identified by gradual change in epithelial thickness and basement membrane organisation (integrity) from the normal to pathological. They also identified changes in tumour positive margins including hyper-keratinisation, breach of the basement membrane and dis-organised epithelial structure. Moreover, the tumour spread pattern could be identified on the majority of the interrogated tissue .The use of optical technologies to reshape tissue structures is important in reconstructive and cosmetic surgery. Electromechanical reshaping (EMR) of cartilage is a promising non-invasive technique with potential for broad application in reconstructive surgery. EMR involves applying direct current electrical fields to localized stress regions and then initiating a series of oxidation-reduction reactions, thus effecting a shape change. Previous EMR studies have focused on macroscopic structural measurements of the shape change effect or monitoring of electrical current flow. OCT provides a means to gauge structural changes in the tissue matrix during EMR. Chen et al. described the application of OCT to image the EMR process to improve our understanding of the mechanisms of action involved and potentially facilitate optimization of this process .Furthermore, in 1992, laser-induced stress relaxation in cartilage was identified. This led to the development of non-ablative laser reshaping of cartilage. Laser septochondral correction is non-invasive, bloodless, painless procedure which takes only 10 minutes to complete and can be performed in outpatient settings. The efficacy and safety of this technology can be improved with the feed back control system measuring temperature and stress distribution in the course of laser treatment. Sobol et al. presented recent results of the research and clinical applications of the technology and equipment for laser reshaping of cartilage in the ENT in 120 patients. The positive results were obtained for 95 percent of the patients in two years follow-up .Grafts obtained from peripheral regions of costal cartilage have an inherent tendency to warp over time. Laser irradiation provides a potential method to control the warping process, thus yielding stable grafts for facial reconstructive surgery. Foulad et al. proposed a model for assessing the effect of laser irradiation on the warping process of costal cartilage using optical technology .The therapeutic use of optical techniques ranges from the direct use of optical wavelengths for delivering treatment to the use of light to specifically activate photo-chemicals to affect tumour lysis with minimal bystander tissue effects. Since many of these technologies are surgically or microscopically directed, the accuracy and resolution of the treatment volume far exceeds that obtained by radiotherapy.Stepp & Betz showed the feasibility of semi-quantitative endoscopic guided perfusion measurements using ICG-angiographies in 25 patients with free-tissue transfer to the upper aero-digestive tract. The method was shown to be easy to perform with no adverse events. A method for simultaneous ICG-fluorescence and white light imaging was presented. The team suggested that the methodology was suited to situations with questionable flap vasculature Doppler signals, or when flaps are otherwise difficult to monitor ,25.Lasers have been used by a number of researchers to close wounds in controlled laboratory tests over the last 15 years. Larson et al. presented their experience using a device to fuse tissue membranes as an alternative to sutures or staples for the coaptation of mucoperichondrial membranes. Coaptation is accomplished through the controlled application of laser heating to induce protein denaturation and subsequent renaturation across the interface. They identified the important parameters involved in fusing biological tissues using radiation from laser sources following computational modeling of the fusion process based on engineering first-principles from heat transfer, fluid dynamics and optics, and from experimental results on a particular tissue system .2 laser operated with a handheld hollow waveguide can consistently produce cochleostomies without damaging the residual auditory function. Fishman et al. demonstrated that for a careful selection of the laser's power, the safety range for the laser is superior to the safety range of drilling. Particularly important is the finding that multiple laser pulses through the same cochleostomy do not further increase the initial compound action potential (CAP) threshold elevation. Moreover, multiple laser pulses at different locations of the cochlea do not further increase the initial CAP threshold elevation observed after the first laser pulse [An interesting application was presented by Fishman et al. Advancements in implantable auditory prostheses now demand preservation of residual auditory function following the surgery. Atraumatic cochleostomy formation is essential to this goal. Clinically reported hearing outcomes in human implantation are still quite variable in this regard. It was suggested that COer pulse .2 laser in 22 patients which showed immediate hearing improvement and eardrum contraction [Eustachian tube dysfunction is very common and is the predominant cause of otitis media with effusion. Negative middle ear pressure generated by Eustachian tube dysfunction can cause deformation of the collagen layer in the ear drum. Kaylie and Miller presented their findings after laser myringoplasty using the Omniguide hand-held flexible fiber COtraction .2 trans-oral laser microsurgery (TLM) is an emerging technique for the management of laryngeal cancer and other head and neck malignancies. This technique has become more widely used by head and neck surgeons progressively replacing traditional open surgical procedures because it is better at preserving organ function with lower overall morbidity. The CO2 laser is coupled to a micromanipulator and microscope, which provides enhanced tumor visualization and the ability to perform precise tissue cuts, obtain excellent haemostasis, and avoid damaging the surrounding tissues and structures that are transected during open surgical procedures. Armstrong et al. reflected upon their decade of experience in TLM, they felt that the improved instrumentation, demonstration of oncologic effectiveness, clinical experience using TLM and decreased morbidity has led to an increased utilization of TLM by head and neck surgeons. Successful surgery requires adequate visualization, precise cutting, controlled depth of tissue penetration, and ability to obtain tissue haemostasis. The full spectrum of laser power settings, spot sizes and energy pulse delivery modes is utilized to resect mucosa, fat, muscle, connective tissue and cartilage while avoiding inadvertent damage to nerves and large vessels, and obtaining adequate haemostasis [COmostasis .2 laser in the management of oral dysplastic lesions has been put into practice for more than a few years now. The main advantage is the decrease in local tissue morbidity. Very few studies have evaluated recurrence, malignant transformation and overall outcome in patients undergoing such procedure. Jerjes et al. applied CO2 laser in a prospective study of 123 oral dysplastic lesions followed-up for 6.4 years. Recurrence and/or malignant transformation of oral dysplasia were observed following laser surgery. They recommended laser resection/ablation for oral dysplasia to prevent not only recurrence and malignant transformation, but also postoperative oral dysfunction encountered by other conventional modalities. The use of trans-oral robotic flexible CO2 laser with fluorescence and narrow band imaging control was commended [The use of COommended .2 laser resection of T1/T2 N0 OSCC. Tumour clearance was primarily achieved in 73 patients. Follow-up resulted in a 3-year survival of 87.8%. Recurrence was identified in 12% of the patients. The mean age of 1st diagnosis of the recurrence group was 76.4 years. Most common oral sites included the lateral border of tongue and floor of mouth. Recurrence was associated with clinical N-stage disease. The surgical margins in this group were also evaluated [The incidence of oral squamous cell carcinoma (OSCC) remains high. Oral carcinomas are the sixth most common cancer in the world. Squamous cell carcinoma of the oral cavity has a poor overall prognosis with a high tendency to recur at the primary site and extend to involve the cervical lymph nodes. Jerjes et al. followed-up 73 patients for 3 years in prospective study to evaluate the oncological outcomes following trans-oral COvaluated .Vocal fold scarring can arise from disease or post-surgical wound healing and is one of the predominant causes of voice disorders. Focused ultrafast laser pulses have been demonstrated to create tightly confined sub-surface ablation in a variety of tissue, including vocal folds. Ben-Yakar et al. demonstrated how the unique ability of ultrafast laser ablation to create sub-surface vocal fold microsurgeries could be used for eventually creating a plane in tough sub-epithelial scar tissue into which biomaterials can be injected. They found that the use of relatively high repetition rates, with a small number of overlapping pulses, is critical to achieving ablation in reasonable amounts of time while still avoiding significant heat deposition. Additionally, they used multi-photon fluorescence of the ablation region and SHG imaging of collagen fibers to obtain visual feedback of tissue structure and confirm successful ablation .Analogous to 3D dosimetry planning for radiotherapy attempts are being made to plan interstitial photodynamic therapy (iPDT), using multiple linear light sources positioned within the tumour. In an on-going feasibility study in the Netherlands, 16 patients with incurable SCC at the base tongue have been treated with iPDT as a last treatment option. Preliminary results are encouraging with a long-term complete response in 8 out of 16 patients who have failed standard treatment. There is strong evidence that the partial responders are a direct result of inadequate light delivery .Accurate light dosimetry has not yet been performed during iPDT in the head and neck. van Veen et al. proposed the development of dedicated iPDT verification and planning technology to improve the clinical response and reduce the occurrence of side effects. Their results so far indicate good conservation of functions i.e. swallowing, and excellent local control of the tumour. Interstitial PDT may offer an excellent alternative or adjuvant for conventional treatment modalities .Photodynamic therapy with m-THPC is an established treatment for superficial squamous cell carcinoma and is also being considered for treatment of larger head and neck tumors. Recently, clinical implementation of m-THPC-mediated PDT in the head and neck has not been optimal; a subset of patients has experienced incomplete response. It is well-understood that sufficient quantities of light, drug and oxygen must be present in the targeted tissue in order to deliver sufficient damage. This requirement is complicated by variations in the tissue optical properties and in the photo-sensitizer uptake rates; however, most clinical protocols do not measure the effect of these factors on the PDT dose delivered to individual patients ,35.Kanick and de Visscher et al. described the use of optical techniques developed to monitor PDT treatments in pre-clinical models into the clinical treatment of head and neck cancer. Their techniques incorporated reflectance and fluorescence spectroscopic measurements into the PDT-treatment protocol. They found that spectral analysis allowed the extraction of m-THPC concentrations and the quantitative determination of tissue physiological parameters that are important to the PDT-delivered dose (i.e. blood volume and hemoglobin saturation). They described the practical and technical challenges of translating these techniques into the clinical setting ,35.Photodynamic therapy, the fourth oncological interventional modality has proved its successfulness in the management of variety of pathologies involving the human body. University College London (UCL) researchers evaluated the outcome following ultrasound-guided iPDT of pathologies involving the head and neck region as well as the upper and lower limbs in 110 patients. Clinical assessment showed that more than half of the patients had "good response" to the treatment and a third reported "moderate response". Radiological assessment comparing imaging 6-week post-PDT to the baseline showed moderate response in half of the patients and significant response in 20% of patients .Optical technologies can be used to activate therapy in a particular location directed by imaging modalities to improve co-location of therapy to disease states. Photodynamic therapy (PDT) is a minimally invasive surgical intervention used in the management of tissue disorders. It can be applied before, or after, any of the conventional modalities, without compromising these treatments or being compromised itself. PDT is valuable for potentially malignant disorders. Hopper et al. on a study of 147 patients showed that 5-ALA-PDT and/or mTHPC-PDT offer an effective alternative treatment for potentially malignant oral disorders. It is associated with excellent functional and cosmetic results and can be used in conjunction with other standard therapies .Shafirstein et al. further showed the safety and efficacy of photodynamic therapy (PDT) in the treatment of oral leukoplakia with 5-aminolevulinic acid (5-ALA) and pulsed dye laser (PDL) confirmed with fluorescence diagnosis system. They determined that high power laser activation allowed completing the laser therapy within 1-3 minutes with a significant response in up to 46% .is and T1, with cure rates of 90% with follow-up to 236 months. The advantage of PDT for early carcinomas of the larynx is the ability to preserve normal endo-laryngeal tissue while effectively treating the carcinomas. This results in improved laryngeal function and voice quality. Furthermore, PDT requires a short duration of therapy as compared to radiation therapy. PDT is repeatable and carries less risk than surgical therapy and is performed as an outpatient non-invasive treatment. Importantly, the use of PDT does not preclude the use of radiotherapy or surgery in the future for new primary or recurrent disease [Professor Biel presented an excellent account of the clinical application of photodynamic therapy for ENT cancers. Carcinoma of the larynx accounts for 25-30% of all carcinomas of the head and neck. Early carcinomas of the larynx (Tis or T1) and severe dysplasia are presently treated with either radiation therapy or surgery alone. Photodynamic therapy has been demonstrated to be effective in the treatment of early carcinomas of the larynx, T disease .Within oro-pharyngeal oncology the management of base of tongue carcinoma continues to be a major challenge in head and neck oncology especially after chemo-radiation failure and the poor reconstructive prospects of total glossectomy with laryngectomy as the remaining salvage option. Without advances in pathological confirmation of previously irradiated fibrotic tongue base tissue the efficacy of robotic trans-oral laser resection is still unproven but very promising. Jerjes et al. evaluated the outcome following ultrasound-guided interstitial photodynamic therapy (US-iPDT) of stage IV tongue base carcinoma in 33 patients followed-up for 18 months. Their clinical assessment showed that two-thirds of the patients had "good response" to the treatment and a third reported "moderate response" .Jerjes et al. also described their experiences with a phase I dose escalating study of photochemical internalization (PCI), which is a novel technology that facilitates the delivery of oncotoxic macromolecules into cytoplasm. The initial mechanism and practical application was described by Berg et al. in 1999. The group evaluated the safety and tolerance of the photo-sensitizer (amphinex) that is used to initiate the photochemical internalization process with bleomycin as the chemotherapeutic agent. The most striking finding was the dramatic tumour responses. The starting dose of Amphinex for the study was set at a level not expected to trigger a PCI response, however there appeared to be a localized synergistic effect with photo-activation .in vivo by Rhee et al. using H. Influenza biofilms with over 66% resolution of otitis media, one of the most common childhood diseases [It is now known that the presence of biofilms in the upper aero-digestive tract prevents the adequate treatment of infections because the infecting agents remain sequestered in an environment away from circulating or topical agents such as antibiotics. The treatment of these recidivist infections is difficult although the use of selected detergents has shown promise. An alternative treatment option is the use of PDT which was shown to be effective diseases .Naturally the next step in the utilization of optical technologies is in the shaping and control of nano devices. An innovative use of optical technology in the activation of nano-devices to promote chondrocyte growth across Ti:Sapphire Femto second laser microstructured titanium prosthesis coated with bioactive proteins was shown by Ilgner et al. to improve bio-integration and sound transmission .In summary, we briefly outlined some of the excellent evidence presented in the 2nd Scientific Meeting of the Head and Neck Optical Diagnostics Society (HNODS) in San Francisco initially relating to disease diagnostics, including detection and guidance for biopsies and treatment and then focusing upon the therapeutic use of optical technologies either directly or by activating treatments.The authors declare that they have no competing interests.All authors have contributed to conception and design, drafting the article or revising it critically for important intellectual content and final approval of the version to be published.


Bone involvement in human cystic echinococcosis (CE) is rare, but affects the spine in approximately 50% of cases. Despite significant advances in diagnostic imaging techniques, surgical treatment and introduction of pharmacological therapy, spinal echinococcosis remains associated with a high degree of morbidity, disability and mortality.We systematically reviewed the published literature of the last five decades to update and summarize the currently existing data on treatment, follow-up and outcome of spinal CE. Spinal cystic echinococcosis (CE) is a rare but malignant form of a truly neglected tropical disease. Despite modern diagnostic imaging techniques, the advances in surgery over the last decades and the availability of pharmacological therapy, the clinical management of spinal CE cases remains a challenge for the treating physician. Ten years after the last extensive review on the topic was published by Pamir et al. , we aim to provide clinicians with a systematic review and comprehensive update on spinal CE to help them deal with the often very complex clinical management of these patients. By systematically reviewing all published case reports and case series of spinal CE from 1965 until now, we summarized and analyzed the existing data on treatment, follow-up, and outcome of the disease and discuss the findings in light of the existing data. This is due to the impossibility of removing by surgical means all diseased bone, especially if the vertebral bodies are affected, to the multiplicity of extra-osseous cysts, to the certainty of recurrent pressure on the cord…’  Echinococcus granulosus, is a cosmopolitan parasitic zoonosis. In the accidental human intermediate host, the characteristic cystic lesions are mainly found in the liver (∼70%) and the lungs (∼20%), but virtually any part of the body may be affected, including the bone (∼0.5–4%). The central nervous system  and the vertebral column (which is involved in ≥50% of the ∼0.5–4% of cases affecting the bone) Hydatid disease or cystic echinococcosis (CE), caused by the larval stage of the cestode le cancer blanc’ ‘Spinal CE’  is associated with a high degree of morbidity, disability, and mortality and the prognosis has often been compared to that of malignancies  being of vital importance. Perforation of the cyst(s) during an operation may lead to systemic dissemination and more critically to local seeding which results in chronic recurrence. Curative surgery remains difficult with bone involvement as infiltration of the bone hampers unruptured and complete resection of the cysts and high recurrence rates plague the long-term outcome Besides surgery, the only other treatment option for spinal CE is antiparasitic therapy with benzimidazole compounds. Since the introduction of mebendazole (in the 1970s) and albendazole (in the early 1980s), surgery with concomitant and subsequent benzimidazole administration became the widely accepted treatment standard and in cases where surgery is not possible, these drugs remain the only treatment option.With recurrences presenting many years or even decades after initial treatment of spinal CE, the assessment of treatment outcome remains difficult. Very few retrospective and even fewer prospective long-term follow-up studies are currently available.We systematically reviewed the published literature of the last five decades for case reports and case series and analyzed and summarized the existing data on treatment, follow-up, and outcome of spinal CE.We performed a PubMed (MEDLINE) search of the literature using the key words ‘spinal echinococcosis’, ‘spinal hydatidosis’, ‘spinal hydatid disease’, ‘spinal echinococcal cyst’, ‘spinal cystic echninococcosis’ and reviewed the obtained references published from 1965 until July 1st 2012  case reports on spinal CE eligible for analysis. The collected data included cyst location(s), anatomical structures involved , treatmeTo evaluate the clinical outcome, follow-up time, and recurrence rates of spinal CE with regard to the involved anatomical structures the cases were divided into intradural- extramedullar CE, extradural-extraosseous CE and osseous CE . The extOf the 367 publications identified by electronic search, 189 publications  were included in the analysis .Data on the treatment approaches, details on the surgical procedures, and data on the use of adjunct medical treatment are shown in decompression of a compromised spinal cord and stabilisation of a compromised spinal column. Almost two centuries after Reydellet performed the first surgical intervention on a patient with spinal CE (1819), surgery remains the treatment of choice Patients with cysts confined to the intradural space typically present with acute to subacute compression of the spinal cord and require urgent decompression. Intradural cysts are approached posteriorly via laminectomy followed by durotomy. The complete resection of the cysts without rupture is considered curative and feasible in most cases, even in the presence of adhesions to surrounding tissue complete resection and unruptured resection) might explain the higher recurrence rate of extradural-extraosseous CE: the higher frequency of multiple cysts and the higher rate of intraoperative cyst rupture. In a large review on CE of the central nervous system, Altinoers and colleagues found an intraoperative rupture rate of 16.9% for intracranial lesions and 44.4% for intraspinal cysts, which they attributed to the discrepancy between the rather narrow space in spinal CE with close bony boundaries and the often multiple spinal lesions The spectrum of extradural-extraosseous CE ranges from single epidural or paravertebral cysts to large dumbbell formations and cases with extensive soft tissue infiltration. As all epidural cysts and the majority of dumbbell cysts present with spinal cord compression, decompression by laminectomy is almost always part of the surgical management. To reach paravertebral lesions, an anterior approach is usually needed. In a case where complete excision of an intact dumbbell cyst was not feasible, intraoperative incision and aspiration with adjacent resection of the reachable cyst wall has been described (without recurrence over 18 months follow-up) In spinal CE involving bone, the infiltrative nature of the microvesicular lesions does not allow for unruptured resection of the cysts and therefore spillage of their contents is inevitable If possible, radical surgery is advocated and although often not precluding disease progression, it has been shown to prolong survival in selected cases A major limitation of the available data on recurrence of spinal CE is the overall short follow-up period throughout the literature  and onlyIn vitro studies have demonstrated a dose- and time- dependent effect: the higher the concentration and the longer the exposure time, the greater and faster the scolicidal effect in vitro studies, the use of hypertonic saline with concentrations lower than 20% appears to be questionable. The use of 20% hypertonic saline in spinal CE has been reported and appears to be safe even for intradural irrigation Various scolicidal agents are routinely used in surgery and percutaneous treatment of visceral CE to sterilize the cysts at intervention, with 95% ethanol and 20% hypertonic saline being the most frequently used solutions Besides leading to disease recurrence, the spillage of cyst content during surgery may provoke various hypersensitivity reactions, ranging from pruritus, urticaria, rash, edema, bronchospasm, and gastrointestinal symptoms to hypotension and fatal anaphylactic shock Therapy with benzimidazole derivatives has shown to be effective in visceral CE Data on the efficacy of benzimidazoles in osseous CE is scarce and the contribution of these drugs to cure or even prevent recurrence in vertebral CE is frequently debated However, various publications have reported favorable results attributed to medical treatment: several authors have used albendazole in patients with inoperable spinal CE  and someAmong the reviewed cases, adjunct pharmacotherapy was used in 98.8% of all cases . In the In the absence of pharmacokinetic data on benzimidazoles in bone or spinal soft tissue, most authors use the dosages recommended by the World Health Organisation (WHO) for visceral CE  by coadministration of cimetidine. However, data on interactions of cimetidine with intestinal absorption and hepatic metabolization of albendazole remains conflicting and the issue controversial Medical treatment with albendazole might not be able to cure or prevent recurrence of spinal CE, but it remains the only treatment option for inoperable patients and the use of drug therapy in conjunction to surgery is generally considered useful to decrease the risk of recurrence, delay recurrence and prevent seeding from intraoperative cyst spillage.Besides benzimidazoles, few other medical treatment options have been tried in osseous CE and their role remains to be defined:Among the reviewed cases, we found four publications where albendazole plus praziquantel combination therapy was used  [35], [3Three publications on five cases of osseous CE and adjunct nitazoxanide treatment have been published Puncture of the cyst, Aspiration of the cyst fluid, Injection of a scolicidal agent, and Re-aspiration of the cyst content) has been reported  extending into the spinal canal and causing severe spinal cord compression. The intervention led to rapid decompression and clinical improvement. No adverse events were observed and follow-up over one year showed favorable imaging results with complete resolution of clinical symptoms. The authors concluded that percutaneous treatment might be particularly beneficial in cases with extensive disease where radical removal is impossible Ozdemir and colleagues reported the use of PAIR in a patient who had undergone complex surgery for thoracic spinal CE before  and presented with severe paraparesis due to recurrent disease. Two vertebral cysts extending into the spinal canal and causing severe spinal cord compression were successfully treated by bilateral transpedicular interventions. No adverse events were observed and follow-up over six months showed favorable imaging results with complete resolution of clinical symptoms. The authors concluded that percutaneous treatment should be considered in cases where prior surgical interventions aggravate re-operation E. multilocularis larval growth E. multilocularis infection with failed multiple surgical procedures and medical treatment has been published In 1965 Fitzpatrick reported the use of radiotherapy in a case with extensive spinal CE and noted that no apparent benefit of this treatment accrued Despite significant advances in diagnostic imaging techniques and surgical treatment, spinal echinococcosis remains associated with a high degree of morbidity, disability and mortality.decompression of a compromised spinal cord and stabilization of a compromised spinal column being the two primary tasks.Surgery is the treatment of choice with The long-term outcome depends on complete resection of all parasitic lesions, which is frequently hampered by the infiltrative nature of the disease.Recurrence rates of spinal CE are high, especially in cases with vertebral bone involvement.The currently existing data on follow-up of spinal CE cases is largely insufficient to judge the long-term outcome of surgery.Besides surgery, the intraoperative use of scolicidals and the pre-, peri-, and postoperative use of albendazole is currently considered the treatment standard of spinal CE.The role of combination drug therapy, percutaneous treatment and radiotherapy in spinal CE remains to be defined.Checklist S1PRISMA checklist. 27-item checklist for systematic reviews.(DOC)Click here for additional data file.Diagram S1PRISMA flow diagram. Flow of information through the different phases of the systematic review.(DOC)Click here for additional data file.References S1Reference list of included and excluded publications.(DOC)Click here for additional data file.


Modern people are still influenced by the mind-body dualism of Rene Descartes. Some of these people said "Anxiety aggravated the symptoms of these patients," a notion that most people probably consider natural. By contrast, I would like to criticize this concept because anxiety is posited as an independent driving force that actively changes one's body. However, anxiety per se is a subjective feeling produced by the brain and somatic signals from the body. Actually, neural activities in the central and autonomic nervous systems along with endocrine and immune function change the body. From this point of view, anxiety is not the CAUSE of mind-body changes but the RESULT of them. The origin and synthetic processing of emotion are more important than simple idea that the "mind" directly changes the body. Descartes' mind-body dualism conceals, in our view, how diseases should be recognized and analyzed.Functional gastrointestinal disorders are useful for illustrating how the rationale of "nervism" of my notion is manifest. In particular, irritable bowel syndrome (IBS) is a prototype of functional gastrointestinal disorders , and theThe clinical usefulness of psychological treatments for IBS patients is evidence of the rationale of the biopsychosocial model. The theoretical background of psychotherapies for IBS is as follows. First, IBS patients have deranged life styles characterized by more perceived stress, more irregular sleep and more irregular meals . ReductiThere is evidence from a systematic review and meta-analysis of rigorously executed trials on IBS that psychological treatment in general is effective for IBS . HypnothIBS: irritable bowel syndrome; CBT: cognitive-behavioral therapyThe authors declare that they have no competing interests.


Congenital fibrosis of the extraocular muscles (CFEOM) describes a group of rare congenital eye movement disorders that result from the dysfunction of all or part of the oculomotor (CN 3) and the trochlear (CN 4) nerves, and/or the muscles these nerves innervate.To describe the clinical and neuro-radiological findings in three patients with CFEOM and review literature with respect to clinical features, genetics and management of this condition.A retrospective chart review was performed of three Omani patients who had been diagnosed with CFEOM in our institution. All patients had undergone standardized orthoptic and ocular evaluations and magnetic resonance imaging (MRI) of the orbits and brain.The three patients (age range nine months - 10 years) presented a history of congenital strabismus. All patients had severe bilateral ptosis and mild to moderate visual impairment secondary to the ptosis and astigmatism. Two of three patients demonstrated a positive jaw-winking phenomenon. A moderate to large angle exotropia with varying amount of hypotropia and limitations of almost all the extra ocular muscles was noted. Patient 3 was also developmentally delayed. MRI brain and orbit showed abnormalities of the extraocular muscles in two patients and brain malformation in one patient.CFEOM is a rare, congenital, and non-progressive disorder with multiple extra ocular muscle restrictions. CFEOM can be associated with neuro-radiological abnormalities; its diagnosis and classification is defined by clinical characteristics and genetics. Options for treatment are limited and difficult. CFEOM is the term used to describe several different inherited strabismus syndromes which manifest as congenital restrictive ophthalmoplegia (restriction of globe movement in one or more fields of gaze), affecting extraocular muscles innervated by the CNIII and/or CNIV. The term Congenital Cranial Dysinnervation Disorders (CCDDs) was coined to refer to the innervation disorders of the extraocular muscles. The variIn this paper we describe the clinical and neuro-radiological findings in three patients with CFEOM who presented to us with a history of congenital strabismus and ptosis, and review literature with respect to clinical features, genetics and management of this condition.A retrospective chart review was performed of three Omani patients who had been diagnosed with CFEOM in our institution between the period 2003–08. All patients had undergone standardized orthoptic and ocular evaluations. Magnetic resonance imaging (MRI) of the orbits and brain was performed in all patients as part of the evaluation of patients with CFEOM.[This study was approved by the Departmental Research Committee.Three Omani patients in the age range of nine months to 10 years were referred for evaluation and diagnosis of complex strabismus. The ocular deviation had been noted in all the three patients from birth. Patient 3 was also developmentally delayed. While patient 1 had undergone bilateral frontalis suspension for congenital ptosis, none of the others had received any treatment.All the patients had an abnormal head posture (mainly chin up), a lack of facial expression, and complete to severe bilateral ptosis. Two of three patients demonstrated a positive jaw-winking phenomenon. Mild to moderate visual impairment secondary to ptosis and astigmatism was noted in all of them. Orthoptic examination showed moderate to large angle exotropia with varying amount of hypotropia and limitations of almost all the extra ocular muscles, with relative sparing of the lateral recti Figures  and 2. AAll the patients received optimal refractive correction and are under follow-up.CFEOM is a rare, congenital, and non progressive disorder with multiple extra ocular muscle restrictions. Its diagnosis and classification is defined by clinical characteristics and genetics. Based on clinical features and genetics, CFEOM can be classified into three types . BilaterCFEOM can be associated with neuro- radiological abnormalities, and neuroimaging has been recommended as part of the evaluation of patients with CFEOM to rule out any intracranial or orbital pathology. UnilaterCFEOM is not easy to treat. Any refractive error and amblyopia should be corrected. Due to the extreme chin up posture adopted by some of the patients with CFEOM, eccentric viewing through the corrective lenses is commonly encountered, contributing to a sub optimal refractive correction. This might underlie the reduced visual acuity seen in our patients. Significant changes have been observed in refraction following extraocular muscle surgery secondary to a change in magnitude and direction of the force exerted by the muscles on the globe.The surgical correction of strabismus and ptosis in CFEOM is challenging. Strabismus surgery is always attempted before ptosis correction. The expectations of strabismus surgery should be realistic and parents and patient should be well informed about these expectations. Very large recessions (12mm) of the affected muscles may be indicated. In CCDDs, resections of extraocular muscles are usually avoided from fear of worsening the enophthalmos. A forcedIn conclusion, CFEOM is a rare, congenital, and non-progressive disorder with multiple extra ocular muscle restrictions. CFEOM can be associated with neuro- radiological abnormalities; its diagnosis and classification is defined by clinical characteristics and genetics. Options for treatment are limited and difficult, and results of surgery are unpredictable.