The insertion of an endotracheal tube (ETT) in a patient of esophageal atresia (EA) with trachea-esophageal fistula (TEF) can be challenging for even the most experienced of anesthesiologist. Incorrect placement, if not detected on time, can have the most devastating complications. The correct placement of an endotracheal tube is dependent on the anatomy and morphology of the fistula. Holzki et al [1] in their study of bronchoscopy on 113 patients of EA with TEF reported that in 11% of patients, the fistula was below the level of carina, in 22% the fistula was within 1cm of the carina while in 67% the fistula was 1cm above the carina. Furthermore, these patients sometimes have other associated congenital anomalies such as tracheomalacia and vascular ring that require additional intervention.The anesthetic and surgical management of neonates with EA with TEF focuses on ventilation of the lungs while avoiding ventilation through the fistula. The mainstay of airway management focuses on careful tracheal intubation beyond the fistula with avoidance of muscle relaxants and positive pressure ventilation until the fistula has been ligated. Gastrostomy, either preoperatively under local anesthesia or soon after the induction of general anesthesia is sometimes used to decompress the stomach and prevent gastric distention.[2]Special attention to placement of the endotracheal tube in the trachea is warranted. The incorrect placement of an ETT can cause increased morbidity by ineffective ventilation as a result of migration of ETT in the fistula. The additional gastric distension would lead to an increased intra-abdominal pressure and potentially cause decreased venous return with hemodynamic compromise as well as restriction of diaphragmatic excursion with significant respiratory embarrassment. Gastric distension can also result in the aspiration of gastric contents via the TEF causing aspiration pneumonitis. Aspiration pneumonitis alone has accounted for up to 50% of the perioperative morbidity and mortality in this patient population.[3] Thus theoretically, the sooner the TEF is closed, the less likely are any of the predictable complications.Techniques of Endotracheal Tube Placement:The ideal method of intubation is placement of the tracheal tube tip beyond the fistula. This facilitates adequate ventilation and prevents gastric insufflation. However, this is not always possible especially in large low lying fistulas. Various techniques have been advocated for accurate endotracheal tube placement and depend on the type and site of fistula, pulmonary status and co-morbid conditions. Direct laryngoscopy or auscultation may not be confirmatory for correct placement of the ETT. Also, a properly placed ETT at the beginning of the case may slip into a large fistula. This can happen most frequently during lateral positioning of the patient for thoracotomy or thoracoscopy.[4] Role of Bronchoscopy:Preoperative bronchoscopy may help the anaesthesiologist and the surgeon to assess the size and location of the TEF and plan for the best airway management strategy. It provides information about the exact size of the fistula, its location, and other coexisting airway anomalies, including the presence of proximal fistula. Additionally, it is also be useful to confirm ETT placement after endotracheal intubation and intra-operatively in the event of any cardio-respiratory instability or ETT dislodgement. The routine use of preoperative bronchoscopy by Aztori et al modified the surgical approach and management of 24% patients.[4] Most tertiary care centres in the west advocate the use of either a rigid or flexible bronchoscope for the identifying of the site and anatomy of the fistula as well as for guiding endotracheal tube placement.[6] Flexible bronchoscopy can be used to confirm proper placement of the ETT and rule out any migration of the endotracheal tube with position changes. In the event of intra-operative tube migration and subsequent hypoxia urgent bronchoscopic evaluation and re-positioning of the ETT is advocated even during thoracotomy. The rigid bronchoscope offers the possibility to ventilate the patient while also visualizing the airway. Other adjuncts in case of continued cardiorespiratory instability include needle decompression of the stomach and pleura as well as occlusion of the fistula with a balloon via emergent gastrostomy or via bronchoscopy.[7-10]Considering the benefits conferred by bronchoscopy and given the wide-spread availability of this equipment, it should be considered standard practice in all patients of EA with TEF.Minimal Invasive Repair of TEF:Minimally invasive surgical techniques are being used increasingly for the repair of EA with TEF in neonates. Traditional repair through a right dorsolateral thoracotomy has major disadvantages, including a large scar, significant postoperative pain, and a high degree of scoliosis and shoulder girdle weakness later in development. An advantage of minimally invasive surgery is superior visualization of the fistula and the surrounding anatomy through the thoracoscope. However, this new approach poses extra challenges to the anesthesiologist because of the requirement for collapsing a lung during the thorascopic repair. Thus, the anesthesiologist needs to isolate not just the TEF, but also a mainstem bronchus during the procedure.Airway management and placement of ETT:The correct placement of ETT below the level of fistula is crucial during endotracheal intubation and prior to ventilation. Therefore, spontaneous respiration is maintained during induction with inhalational anaesthetic agents and muscle relaxants are administered only after the ligation of the fistula so as to prevent gastric insufflations from positive pressure ventilation. Alternatively, a rapid sequence intravenous induction without positive pressure mask ventilation may be the preferred mode of induction followed by rapid securing of the airway.[12] Several different methods for securing the airway and controlling the fistula have been described. Traditional technique:The technique most commonly used involves insertion of the ETT deep endobronchial followed by gradual withdrawal till the ETT is just above the carina and bilateral equal breath sounds are heard on auscultation of the chest.[2] Additionally, the ETT is rotated so the bevel faces anteriorly and away from the fistula which is most commonly located on the posterior wall.[10] In this manner, the tip of the ETT is placed beyond the fistula and the anteriorly placed bevel ensures that the shaft of the endotracheal tube occludes the fistula. For obvious reasons, an ETT without side holes is recommended. The correct placement maybe confirmed either by auscultation or by bronchoscopic evaluation. In case a gastrostomy has been performed previously, the end of the gastrostomy tube may be placed underneath a water seal. The presence of bubbling indicates ventilation through the fistula, which will occur if the tip of the ETT is proximal to the opening of the fistula. The ETT should be pulled back almost until gas begins to bubble from the end of the gastric tube , then re-advanced until the bubbling stops.[2] A capnograph inserted into the gastrostomy tube will indicate the same thing by showing tracing of respiratory movements and persistently elevated levels of end tidal carbon dioxide levels.[13]This technique is especially useful in emergency situations and when TEF is associated with duodenal atresia.Use of Fogarty Balloon Catheter:Use of Fogarty balloon catheter to occlude the fistula is another method commonly employed. After the induction of general anaesthesia, a suitable sized Fogarty arterial embolectomy catheter is placed through the vocal cords under direct laryngoscopy and then the bronchoscope is placed through the cords. The Fogarty balloon-tipped catheter is then advanced into the TEF. The Fogarty catheter often preferentially passes into the TEF because of the dependent position of the TEF. The fistula is then occluded by inflating the balloon-tipped catheter. The bronchoscope is removed, and the trachea is intubated with an oral ETT in the standard fashion and the ETT is placed in the trachea alongside the Fogarty catheter.[9] The insertion of the Fogarty catheter can be from either the tracheal route (2-3Fr) or via the gastrostomy (5Fr).[14]However, apart from being technically complex, this technique has its own problems. The occlusion of the fistula with a Fogarty embolization catheter may or may not be effective. In order to place the Fogarty catheter with a rigid bronchoscope, it would be required to interrupt ventilation and the size of the bronchoscope may limit use of the catheter. In the event of the Fogarty catheter getting dislodged intra-operatively, it may occlude the trachea making ventilation impossible. Also, the catheter can damage the esophageal mucosa at the balloon site.[10] Further, gastrostomy is not routinely performed in patients with no other complications, so, retrograde occlusion through a gastrostomy may not always be an option.[15] Despite the above mentioned drawbacks, Fogarty catheter is a useful aid in isolating large fistulas or those located near the carina.Use of Double Fogarty Catheters:Placing two balloon-tipped blockers, one in the fistula and the other in the right mainstem bronchus, is a viable technique for thoracoscopic EA with TEF repair when the fistula is at or very close to the level of the carina and one lung ventilation is required. In a case report [16] on a full-term neonate with a type C type EA with TEF (fistula at the level of the carina), two Fogarty type balloon-tipped embolectomy catheters were placed alongside the ETT to successfully achieve the goal of blocking ventilation of the fistula and the right lung. The balloon of one catheter blocked the fistula while the other was inserted into the right mainstream bronchus to occlude the ventilation of the right lung. The use of fibreoptic bronchoscopy greatly facilitated placement of the blockers. The patient made an uneventful recovery.[16]The disadvantages of bronchial blockers include the possibility of mucosal damage (though not yet seen), retrograde migration of either blocker into the tracheal lumen, resulting in partial or complete airway obstruction. The insufficient blockade of the mainstream bronchus may lead to partial ventilation of the collapsed lung and bronchial rupture.[17]Use of Cuffed ETT:The cuff of an ETT can be similarly used to block the fistula. Immediately following the insertion of the ETT, a 2.5 mm flexible bronchoscope is inserted into the ETT. The ETT is advanced under direct vision to just above the carina but distal to the fistula. At this location, the cuff on the ETT is inflated to occlude the fistula. Greenberg et al have reported accurate placement of a 3.5mm cuffed ETT with bilaterally equal breath sounds on auscultation and without gastric distension on positive pressure ventilation.[18] Thus, a cuffed ETT may be accurately positioned to exclude the fistula allowing for an easier and safer operation.[12]One lung Ventilation:Many case reports have documented the successful use of one-lung ventilation in term and preterm neonates. After the administration of general anaesthesia, the ETT is facilitated into the left mainstream bronchus till the ligation of the fistula after which it is slowly withdrawn back into the trachea for oesophageal anastomosis. This technique of inserting the ETT into the left mainstream bronchus acts by blocking the fistula and the right mainstream bronchus simultaneously. However, differences in the diameters of main-stem bronchus and the trachea may result in an ETT that fits a main-stem bronchus well but is too small for the trachea while the one that fits the latter is too large for the former. This might predispose to left bronchial edema.[21] In one report, left upper lobe collapse was also seen in deliberate endobronchial ETT placement in neonates to achieve one-lung ventilation.[19] Another disadvantage is occurrence of desaturation during one-lung ventilation in EA with TEF repair.[12] The ETT may need to be retracted several times to ventilate both lungs intra-operatively and subsequent repositioning of the ETT tip back into the left mainstream bronchus requires fibreoptic bronchoscopy, which may be hazardous and cumbersome in a semi-prone neonate, made even more difficult by the sterile drapes separating the small distance between the operative field and the patient’s mouth.Use of a specially designed bifurcated tracheal tube for EA with TEF repair has also been described.[22] This is not a double-lumen tube, and is therefore not suitable for differential lung ventilation.Use of Endobronchial blocker:In neonates with EA and a large carinal TEF, endobronchial blocker has been used to occlude the fistula.[23] The endobronchial blocker is inserted down to the level of the mid-trachea and the proximal trachea was intubated with a microcuff endotracheal tube alongside the blocker, while, the fiberoptic bronchoscope is used to guide the blocker into the fistula. Use of a new 5-Fr endobronchial blocker suitable for use in children with a multiport adapter and fiberoptic bronchoscope has been described.[24] This helps reduce the incidence o hypoxemia and also aids repositioning of the endobronchial blocker intra-operatively.The airway management and ETT positioning in a case of EA with TEF is definitely challenging but is aided to a great extent by preoperative and intra-operative bronchoscopy. Out of the various techniques mentioned above, the traditional technique of endobronchial intubation followed by gradual withdrawal into the trachea remains the most popular amongst anaesthesiologists. The technique of choice must take into account the type and location of fistula, the preoperative chest condition, pulmonary compliance and other associated co-morbid conditions. The positioning of the ETT in the left mainstream bronchus or distal to the fistula may minimize gastric insufflation and improve ventilation as well as surgical field, however, the surgeon and anaesthesiologist must remain vigilant for any inadvertent tube mal-positioning with its catastrophic sequelae at all times.Source of Support: NilConflict of Interest: NoneEditorial Comment: Many pediatric surgeons would disagree with the above recommendation of the authors to place the ETT tip beyond the TEF. Instead, if the tip of ETT is placed just above the TEF, it is easier to identify the lower esophageal segment in the most common variant of EA- type C with distal TEF; it would distend with each breath. However, there is no randomized trial or metanalysis available to suggest the superiority of one over the other.


A comprehensive technique for earthquake-related casualty estimation remains an unmet challenge. This study aims to integrate risk factors related to characteristics of the exposed population and to the built environment in order to improve communities’ preparedness and response capabilities and to mitigate future consequences.An innovative model was formulated based on a widely used loss estimation model (HAZUS) by integrating four human-related risk factors  that were identified through a systematic review and meta-analysis of epidemiological data. The common effect measures of these factors were calculated and entered to the existing model’s algorithm using logistic regression equations. Sensitivity analysis was performed by conducting a casualty estimation simulation in a high-vulnerability risk area in Israel.the integrated model outcomes indicated an increase in the total number of casualties compared with the prediction of the traditional model; with regard to specific injury levels an increase was demonstrated in the number of expected fatalities and in the severely and moderately injured, and a decrease was noted in the lightly injured. Urban areas with higher populations at risk rates were found more vulnerable in this regard.The proposed model offers a novel approach that allows quantification of the combined impact of human-related and structural factors on the results of earthquake casualty modelling. Investing efforts in reducing human vulnerability and increasing resilience prior to an occurrence of an earthquake could lead to a possible decrease in the expected number of casualties. Despite immense efforts invested in disaster risk reduction around the world, earthquakes continue to claim a heavy toll and remain the deadliest natural disaster worldwide, as demonstrated in recent events such as the 2010 Haiti and 2015 Nepal earthquakes .Dense urban population centers are known as highly vulnerable in this context . NeverthFuture challenges in the field of disaster risk reduction thus require a more diverse, people-centered preventive approach. An efficient disaster risk management program should be founded on preliminary evaluation of vulnerabilities and potential risks to the population, structures and infrastructures; such knowledge can be leveraged for improving pre-disaster preparedness and mitigation and for the development of an effective response . Loss-esIsrael is situated along the Dead Sea Fault, which has been the origin of intensive earthquakes causing widespread devastation for over 2000 years. Although no major earthquake has struck the region in the last 90 years, experts forecast that strong tremors might occur in the near future and stress the need for action in the region, which is almost entirely located in a seismic risk zone .The aim of this study is to produce an integrative and interdisciplinary model for estimating earthquake casualties in a high risk area in Israel, using risk factors associated with both the built environment and the population’s characteristics. The model structure is generic and can be applied in different regions depending on their specific population characteristics and available data.The new model was formulated based on the HAZUS casualty estimation model. Several human related factors that were found as increasing the risk of injury and death in earthquakes were integrated into the current HAZUS model; and a sensitivity analysis was performed in order to assess how the addition of these parameters affects the casualty projections.The predictors used in this model were identified based on a previous peer-reviewed systematic analysis aimed to assess individual and household characteristics associated with earthquake-induced death and injury in previous events; the review included studies with an analytical design that reported effect size measures, and the results revealed four risk-factors that increased human vulnerability to earthquakes. These were: gender ; age >65 years); having a physical disability; and belonging to a low socioeconomic status  was calculated  in order to determine the number of fatalities; this number was subtracted from the total number of residents in the census tract (residents with the highest death probabilities were excluded first and so on) and the reminder was then transferred to serve as the basis for step (b)–estimation of expected severely injured, which was performed in the same method as in step (a). Steps (c) and (d) estimated the moderate and slight injuries, again calculated in the same manner. After ending the procedure (following step (d)), the remainder of the residents were defined as uninjured. The entire estimation procedure is detailed in Age was the strongest factor increasing the risk of death in earthquakes, followed by socioeconomic status, physical disability and gender. Individuals aged 65 years and older had the highest combined OR for increased risk of dying in an earthquake of 2.92  compared to younger individuals. Two studies directly assessed the impact of age and gender with regard to the risk of injury; the results indicated that gender has a higher combined OR of 1.7  compared with age . No studies were found that measured the direct impact of socioeconomic status and physical disability on the risk of injury and therefore, the combined effect that was calculated for the risk of death was used for injury as well. The combined effect measures are detailed in The data gathered regarding the rate of risk factors related to individual and household characteristics in the population revealed disparities in different census tracts (neighborhoods) in Tiberias. The difference in the rate of residents older than 65 years in the various census tracts of the city ranged between 1.5%-16.5%. The rate of physically disabled persons ranged between 3.5%-27.5% in different census tracts. Gender distribution was similar among all census tracts . The average annual income of the census tracts residents was compared with the national average and found to be lower than the national average among 10 out of 12 census tracts.The results of the casualty estimation procedure according to twelve census tracts of the city of Tiberias are detailed in When examining the casualty rates among various census tracts, it becomes clear that certain areas bear a heavier casualty burden compared to others. Areas with relatively low rates of vulnerable populations (manifested in the risk factors defined previously) are likely to have almost 10% less fatalities than more vulnerable areas in this regard; for example census tract 24 is expected to have 20% fatalities versus 28% in census tract 33 that include much higher rates of elderly population (over 65) and physically disabled population and are also ranked lower in the socioeconomic index. These differences are also demonstrated regarding severely injured casualties (5% expected in census tract 24 vs. 10% in census tract 33). When examining the predicted values of moderately and slightly injured casualties the differences seem to decrease; the difference between the predicted lowest value and the highest value of moderately injured casualties is 4% and 2% for slightly injured casualties.This paper provides an innovative integrated and interdisciplinary practical approach to estimate the number of earthquake-induced casualties of different severity levels using a combination of human-related and structural factors. The results of the new model were compared with a traditional engineering-based model. The integration of human-related risk factors altered both the general expected number of casualties in a given event and more importantly, the composition of casualties . There was an increase in the overall number of casualties and in the expected number of fatalities, severe and moderate injuries, and a decrease in the expected number of slight injuries. Geographical variability in vulnerability was also demonstrated, as areas of Tiberias with higher rates of at-risk population were identified to be more vulnerable in this regard. When interpreting these results, one should note that since the examined area’s social and demographic attributes has a great impact on the outcomes of the model, two sub-populations located within a small geographical distance may produce different results in the same earthquake simulation. In the current study, the city of Tiberias, is ranked relatively low in the socioeconomic index compared to other municipalities in the country . Since tThe results of the current model along with the evidence from the literature may indicate a potential gap in the estimation process of earthquake-related casualties resulting from the previously missing human characteristics dimension. This conjecture is also supported by other evidence dealing with the level of uncertainty of the traditional HAZUS model evaluated in several validation assessments that manifested among others in inaccuracies of the casualty estimates –36. FurtThe addition of human-related risk factors to the estimation process of earthquake-related casualties is part of a more comprehensive approach of risk assessment ,37, and Several limitations of the current study derive from the scarcity of data regarding the effect size measures of human-related risk factors. Other result from difficulties in obtaining reliable data from areas steeped in chaos . FurtherThe implications and use of this novel approach are wide ranging. Previously, casualty estimation was based solely on engineering methods and damage to the build environment. As suggested by this paper, the expected number of casualties can be estimated utilizing a more comprehensive approach which incorporates social vulnerability of the investigated area.This study demonstrates the use of an innovative approach which takes into account both the built environment and population characteristics to predict earthquake casualties. Such knowledge may lead to more focused investment of efforts in reducing vulnerability of potentially more severely affected populations, prior to an occurrence of an earthquake.S1 Table(XLSX)Click here for additional data file.


Premature birth affects 12.5% of pregnancies, and as a result, intraventricular hemorrhage (IVH) of the brain with subsequent development of hydrocephalus is a major cause of morbidity, mortality, and poor intellectual outcomes. Prospective clinical trials to dissolve IVH clots with intraventricular infusion of tissue plasminogen activator through surgically implanted catheters demonstrated improved intellectual outcome in the survivors but at an increased risk of hemorrhage. A non-invasive method to lyse the clots may result in a reduced risk of subsequent hydrocephalus, and better intellectual outcome for these patients. Magnetic resonance guided focused ultrasound (MRgFUS) delivered through the open fontanel is such a therapy, but requires a versatile transducer positioning system that adapts to the MRI compatible transport and imaging incubator used to manage these fragile neonates.A five degree of freedom MRI compatible robotic device has been designed to precisely position an MRgFUS transducer  for transcranial therapies within the constraints of the neonatal incubator system. Pulsed focused ultrasound (FUS) energy is used to lyse IVH blood clots in the brain of the patient. The robot is used to position the transducer above the head of the patient while the patient is inside the MRI machine. Five ultrasonic, non-magnetic motors are used to actuate the robot. Specially selected, non-magnetic materials are used to construct the robot. A workspace analysis for delivery of the FUS to the intraventricular system of the brain in typical premature neonates was carried out, as were predicted load and speed requirements. A mock-up of the treatment system, with a 3D printed neonatal skull inside the incubator was constructed. The first prototype of the robot was tested for MRI compatibility while the motors were in operation. A master-slave control system, integrated with the MRI imaging system was also designed.Tests of individual components of the robot show that it has the potential for highly accurate targeting with the FUS transducer through the anterior fontanel of a neonatal head within the incubator transport system in the MRI environment.The design meets workspace, load and speed requirements. The activated components do not create significant imaging artifacts or degradation of signal to noise ratio (SNR). Geometric distortions due to large metal objects (such as the drive motors) are negligible at distances longer than half the focal length of the transducer. We conclude from these experiments that the design of the robot is appropriate for transcranial MRgFUS thrombolysis and could significantly improve treatment of IVH in premature infants.


The effect of galanin is mediated through three GPCR subtypes, GalR1-3. The limited number of specific ligands to the galanin receptor subtypes has hindered the understanding of the individual effects of each receptor subtype. This review summarizes the current data of the importance of the galanin receptor subtypes and receptor subtype specific agonists and antagonists and their involvement in different biological and pathological functions.


The analysis of retinal blood vessels plays an important role in detecting and treating retinal diseases. In this review, we present an automated method to segment blood vessels of fundus retinal image. The proposed method could be used to support a non-intrusive diagnosis in modern ophthalmology for early detection of retinal diseases, treatment evaluation or clinical study. This study combines the bias correction and an adaptive histogram equalisation to enhance the appearance of the blood vessels. Then the blood vessels are extracted using probabilistic modelling that is optimised by the expectation maximisation algorithm. The method is evaluated on fundus retinal images of STARE and DRIVE datasets. The experimental results are compared with some recently published methods of retinal blood vessels segmentation. The experimental results show that our method achieved the best overall performance and it is comparable to the performance of human experts. Automated segmentation of retinal structures allows ophthalmologist and eye care specialists to perform large population vision screening exams for early detection of retinal diseases and treatment evaluation. This non-intrusive diagnosis in modern ophthalmology could prevent and reduce blindness and many cardiovascular diseases around the world. An accurate segmentation of retinal blood vessels  plays an important role in detecting and treating symptoms of both the retinal abnormalities and diseases that affect the blood circulation and the brain such as haemorrhages, vein occlusion, neo-vascularisation. However, the intensity inhomogeneity and the poor contrast of the retinal images cause a significant degradation to the performance of automated blood vessels segmentation techniques. The intensity inhomogeneity of the fundus retinal image is generally attributed to the acquisition of the image under different conditions of illumination.Previous methods of blood vessels segmentation can be classified into two categories: 1) pixels processing based methods, and (2) tracking-based or vectorial tracking or tracing methods , , [The experiment results of different retinal blood vessels segmentation methods on the STARE dataset are shown in Tables We also compared the performance of our method on both healthy and unhealthy ocular images. The results of the experiments show that the unhealthy ocular images cause a significant degradation to the performance of automated blood vessels segmentation techniques. Table Similarly to STARE dataset, The performance results of Staal , MendonçFigure We have presented in this paper a new approach to blood vessels segmentation by integrating the pre-processing techniques such bias correction and distance transform with a probabilistic modelling EM segmentation method. We have evaluated our method against other retinal blood vessels segmentation methods on STARE and DRIVE datasets. The overview of the experimental results presented in Tables Our method has an advantage over tracking-based methods because it applies bias correction and distance transform on retinal images to enhance vessel appearance and allows multiple branches models. Also our method achieves better results over pixel processing based methods as it corrects the intensity inhomogeneities across retinal images to improve the segmentation of the blood vessels. This technique also minimises the segmentation of the optic disc boundary and the lesions in the unhealthy retinal images.Djibril Kaba is the first author and has made more contributions, the rest of the authors have made the same contributions.


One of the most important manifestations of mucopolysaccharidosis (MPS) type I, II and VI is a progressive disease of the osteoarticular system. The evaluation of the disease advancement is difficult due to the complexity of symptoms. The characteristic features are progressive limitation of joint mobility and joint pain. These symptoms affect the quality of patient life. A uniform scale has not been developed for these patients.The aim of this study was to use the experience in the evaluation of disorders in rheumatic diseases  in patients with MPS.6 patients with MPS VI were evaluated: 2 with advanced disease, 2 with moderate and 2 with slow progressing disease. The following parameters were selected for assessment: Physician global assessment of disease activity (PGA), Patient/parent global assessment of well-being (PGE), Functional ability (CHAQ), Number of joints with limited movement (LJC) and VAS pain – visual analogue scale for pain.The evaluation results are shown in Table The parameters used in JIA may be applied for assessment of the MPS severity. With their implementation, the progression of the disease and the effect of the treatment can be assessed and compared.None declared


We describe a case of traumatic obturator hip dislocation in an adult. Closed reduction was done under general anesthesia. Post-reduction radiographs showed concentric and congruent reduction of the right hip. Traction was applied for three weeks followed by progressive mobilization and loading. Follow up for two years after the injury showed that the patient achieved a full recovery without any evidence of hip pain or a decreased range of motion. There were no signs of osteonecrosis of the femoral head. The rise of road traffic accidents involving high-energy trauma has increased the incidence of traumatic hip dislocation. Obturator hip dislocations in adults are rare, and only a few cases have been reported in the literature. We describe an adult case of traumatic true obturator hip dislocation.Male patient, 35-years-old, victim of an automobile accident was admitted in our emergency department two hours after. He complained about severe pain in his hip and inability to move the right lower limb. On physical examination he was conscious and hemodynamically stable, the lower limb was found in extension; abduction and external rotation. There were no neurovascular deficits without associated injuries Radiographic examination of the pelvis revealed an obturator dislocation of the right hip. No associated fracture was seen Follow up for two years after the accident showed that the patient was pain free with full range of motion. There were no changes suggestive of avascular necrosis of the femoral head.Anterior dislocations of the hip are divided into two types according to the position of the femoral head, pubic or superior type 1) and obturator or inferior type 2) [ and obtu [ and obObturator dislocations of the hip are uncommon injury, occurring in less than 5% of all traumatic hip dislocations , 3. The Dislocation of the hip is an orthopedic emergency. Closed reduction under general anesthesia is considered as the treatment of choice in traumatic obturator hip dislocations , 7. ReduObturator dislocation of the hip in adults is rare. Its rarity is due to the inherent stability of the joint, its deep position in the pelvis with strong ligaments and bulky muscles around the articulation. Prompt diagnosis and treatment are crucial in the management of these injuries.


In the absence of a national newborn hearing screening program in Italy, parent associations have been working with the Italian Paediatric Federation (FIMP), the Society of Neonatology (SIN) and members of the Italian Society of Audiology and Phoniatrics (SIAF) to promote guidelines, best practice and training courses in early hearing detection intervention that incorporate sensitivity training for professionals working with families of deaf children. The establishment of the Italian Paediatric Federation’s Audiology Network is the result of an international collaboration between parents and medical professionals designed to promote an effective model in developing Early Hearing Detection Intervention Programs (EHDI) that recognize the role of parents as partners in the process. Among other factors, one important component frequently underestimated in most early intervention programs, both in the USA and in other countries, involves the role of parental involvement within the EHDI process.  From scrAfter five years of working region by region in Italy, the network recently held its first National Pediatric Course of Audiology where the parental voice was fundamental in providing sensitivity training and in recruiting the participation of pediatricians with patients diagnosed with hearing loss.In the absence of a Regional Protocol for Newborn Hearing Screening in Sicily, the Association Io Sento offers assistance to families of children with hearing loss. The Association collaborates with health structures and agencies to offer resources that inform, educate and support families regarding diagnosis, school services, the cochlear implant, speech habilitation by using a network created by information technology.


Bacteria are present in all foods, whether they are indigenous or inoculated. They can be beneficial to the quality of foods, responsible for food spoilage, or even pathogens. In solid food products, bacteria are immobilized. They thus grow as colonies entrapped within the food products or on the food surfaces. In both cases, bacteria interact with the solid matrix, sometimes facing difficulties to access the nutrients as nutrients have to diffuse from the matrix to the bacterial colonies. Bacterial development can thus be impaired in solid matrices in comparison to planktonic growth. To control the growth of bacteria in solid foods is then of major importance. In the case of pathogens, it is crucial for safety issues to predict how the bacteria present as initial contaminants will develop. In the case of inoculated bacteria, such as lactic acid bacteria, it is also crucial to control their development because they are responsible for the final quality of the food products. However, studies on the growth of bacteria have been essentially focused on growth in liquid media. Resolute techniques, which include both microcopy approaches and quantitative techniques, have now been developed to observe colonies at the microscopic scale. They allow studying the variation of growth in different contexts either in model growth culture media or in model foods.Jeanson et al.). The second review demonstrates the importance of modeling the growth of bacterial colonies in solids foods despite a lack of knowledge. The different types of models and their potential consequences on decisions are presented and discussed (Skandamis and Jeanson). The third review shows how non-invasive techniques can be used to observe bacterial growth and also quantify the bacterial metabolism in colonies at the microscopic scale . The last review paper shows how microscopy techniques are particularly valuable to increase knowledge about bacterial colonies in model foods and foods. Fluorescent microscopy allows targeting metabolites and understand the physiology of bacteria within colonies .This Research Topic starts with four review papers. A first comprehensive review about bacterial colonies redraws the history of the studies on colonies, synthetizes the conditions of growth in which growth in colonies differs from planktonic growth, and finally presents concepts of the interaction of bacterial colonies with the food matrix in which they grow, with cheese as an example . The following study demonstrates the accuracy of a phenotyping technology based on laser-induced speckle scatter patterns in Bacillus colonies. The authors showed that the distribution of speckle size is modified during the growth of colonies .The five following papers present original results in the field. Using an automated microscope coupled with fluorescence dyes, it was possible to demonstrate that the exposure to an oxidizing disinfectant led to different morphologies of cells depending on the strains and that dead cells were randomly distributed within the micro-colonies , growth rates and metabolism in renneted milk differed from the one observed in liquid milk . The use of fluorescence lifetime imaging was shown to be relevant to investigate the pH micro-heterogeneity in Cheddar cheeses . These results suggest that the surroundings of bacterial colonies within cheeses could differ from homogeneous growth conditions in liquid medium. The last study questioned the access of bacteria in colonies to their nutrients, through the assessment of diffusion of solutes inside colonies. The diffusion of high molecular weight molecules was assessed inside Lactococcus lactis colonies grown in a model cheese. The results led to the conclusion that diffusion of molecules inside bacterial colonies depends on the physicochemical properties of the molecules .The three following studies investigate bacterial colonies of lactic acid bacteria in their food environment in model cheeses or investigate the pH in their surrounding micro-environment in Cheddar cheeses. Physiology and growth of In conclusion, since bacteria mainly grow in colonies in foods, increase knowledge on growth and physiology of bacteria growing as colonies is now a crucial issue. This is achieved by the recent development of non-invasive techniques that allows investigating at the microscopic scale with time lapse and quantitative analyses. Knowledge about the growth and the adaptive response of bacteria to the food environment will continue to grow by addressing the remaining questions about interactions between bacterial colonies and their food environment.SJ: wrote the editorial. AT: revised and improved the editorial.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Nature Communications6: Article number: 752010.1038/ncomms8520 (2015); Published: 07032015; Updated: 01212016.The authors inadvertently omitted Sumit Jaiswal, who was originally included in the Acknowledgements section of this Article and contributed to the cloning of transgenic constructs and the balancing of transgenic flies, from the author list. This author has been added to the author list and removed from the Acknowledgements in both the PDF and HTML versions of the Article.


This overlooks the social and emotional salience associated with hearing the voices of trusted friends and loved ones. Sidtis and Kreiman  write: “Therefore, there are remaining questions about how familiar voices of different types—family members, friends, colleagues, romantic partners—engage the brain during the perception of vocal signals. A number of existing studies have shown evidence for heightened release of oxytocin—a hormone associated with parental and interpersonal bonding—when participants hear the voice of a loved one (Seltzer et al., Recent neurobiological models of speech production have adopted a forward models approach, in which the brain aims to reduce the error between the predicted and actual sensory consequences of a spoken utterance (Guenther, Phonetic convergence describes the phenomenon of interlocutors aligning their acoustic-phonetic pronunciation of speech over a period of spoken interaction, often outside of their conscious awareness (Krauss and Pardo, An improved understanding of how flexible control of the voice affords the attainment of social goals demands investigation of how the talker's intentions are expressed in speech, detected by the listener and used to elicit or guide further social behaviors between interlocutors. Pardo  writes: Studies of vocal identity perception should make more regular and selective use of familiar voices, in order to interrogate the interaction of speech/voice perception systems with other response networks relevant to social interactions. It is important to consider that there are different types of familiar person, for whom the perceptual response may systematically differ. Alternatively, Sugiura  suggestsStudies of speech production mechanisms should consider the intended recipient of the spoken message and their relationship to the talker. Here, neuroimaging techniques may offer a means of investigating the interaction of speech perception and production systems with affective, reward and motivational responses, in both the presence and absence of measurable behavioral changes in the phonetic realization of speech.The advent of improved methodological approaches to brain imaging during speech production (e.g., Xu et al., The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


There are now a number of studies which have analyzed membrane tethers in tissues and organisms which are providing new insights into the role of this class of membrane protein at the physiological level. Here we review recent advances in the understanding of the function of membrane tethers from knock outs (or knock downs) in whole organisms and from mutations in tethers associated with disease.Membrane tethers have been identified throughout different compartments of the endomembrane system. It is now well established that a number of membrane tethers mediate docking of membrane carriers in anterograde and retrograde transport and in regulating the organization of membrane compartments. Much of our information on membrane tethers have been obtained from the analysis of individual membrane tethers in cultured cells. In the future it will be important to better appreciate the network of interactions mediated by tethers and the potential co-ordination of their collective functions  Membrane trafficking is a dynamic process which involves the generation of transport vesicles loaded with cargo and their delivery and fusion to their designated compartments. Vesicle docking represents a key step in this process whereby transport vesicles or carriers are delivered with high fidelity to target membranes. Tethering factors play a central role in the docking process as they mediate the bridging of the vesicle and target membranes. Loss of membrane tethers impacts not only on membrane transport but also in many cases on the organization of intracellular compartments suggesting additional roles for tethers in organelle biogenesis.The majority of membrane tethers are recruited from the cytoplasm by Rab and Arl small G proteins to a defined intracellular location such as the Golgi apparatus or the early endosome. The recruitment of these peripheral membrane proteins provides a dynamic mechanism to establish specialized protein complexes within defined membrane subdomains. Membrane tethers interact with Rabs and SNARES (soluble NSF attachment protein receptors) for co-ordinating docking and fusion. SNARE proteins are crucial for vesicle fusion following the docking event. Membrane docking mediated by tethers provides the first level of specificity as well as promoting the shorter range interaction between SNARE molecules on opposing membranes which then promotes membrane fusion.in vivo studies would not have been predicted from the knowledge of the function of membrane tethers in cultured cells, illustrating the potential limitations of the use of cell lines. Therefore, we think it timely to highlight the recent in vivo studies exploring the roles of membrane tethers in whole tissues and organisms which is the main focus of this review.Membrane tethers interact not only with Rabs and SNAREs but also with other effectors, such as cytoskeletal components, which suggests membrane tethers have functions in addition to the regulation of docking of membrane transport carriers . Coiled-coil tethers are typically hydrophilic homodimeric proteins containing extensive regions of coiled-coil domains; typically there are discontinuities in the coiled-coil domains which are proposed to provide flexible joints in the molecules to allow the tether to mediate docking of bound transport vesicles onto the target membrane. MTCs are a diverse family of proteins consisting of 3 to 10 subunits with sizes up to 800 kDa   thus allowing microtubule nucleation which facilitate Golgi ribbon formation  mutagenesis can result in a loss of function of a gene by the insertion of a nonsense mutation and the production of a truncated protein. Disease causing mutations may be missense or nonsense mutations, resulting in a truncated protein or mutations in the coding region which perturb the binding to one (or more) binding partners. If the tethers are involved in a range of biological functions then the resulting phenotypes of different genetic alterations will likely reflect the consequence of the interactions of the tether, not only with the membrane compartment where the tether is normally localized, but also with specific binding partners. Indeed, the use of different genetic approaches for a given tether is likely to provide complimentary information in unraveling the functions of these molecules.A number of genetic approaches have been used to genetically alter membrane tether genes and these experiments have resulted in a variety of developmental and physiological phenotypes in a range of organisms which have been studied. As membrane tethers have a suite of binding partners, any phenotype observed in whole organisms needs to be interpreted within the context of the consequence of the genetic alteration on the biochemistry of the membrane tether and its interactions with binding partners. Figure Caenorhabditis elegans and Drosophila melanogaster and zebrafish as well as disease causing mutations in humans. Figure The following describes the findings for genetic manipulation of individual membrane tethers of both the secretory pathway and endocytic pathways in mice, cis-Golgi and knockdown in cultured cells has been shown to result in disruption of the normal Golgi structure   gene develop osteochondrodysplasia, cleft palate, and system edema. These rats are born with an abnormal skeletal system  localized to the Golgi apparatus that is involved in mediating retrograde Golgi transport  gene are known to also cause SMA and it has recently been shown that the function of the SMN protein is linked to the Golgi network  is a coiled-coil TGN-golgin (Mori and Kato, C. elegans. However, knockout of Vps51 in C. elegans showed lysosomal defects (Luo et al., GARP is a heterotetrameric complex comprised of 4 subunits—Vps51, Vps52, Vps53, and Vps54 (Conibear and Stevens, Drosophila, knockout of HOPS or CORVET subunits leads to either embryonic lethality (Messler et al., HOPs and CORVET are MTCs localized to the endo-lysosomal system in cells where they act sequentially and coordinate tethering and fusion events at the early/late endosomes and the lysosome (Solinger and Spang, Drosophila are associated with growth and developmental defects. An early study from a gene trap screen in mouse embryonic stem cells identified Sec8 as required for mesoderm induction in embryos (Friedrich et al., Drosophila resulted in early postembryonic lethality and defined a role for the exocyst in endocrine secretion (Andrews et al., Drosophila lead to early embryonic lethality and showed normal protein trafficking along the axons but reduced protein cargo delivery into the plasma membrane (Murthy et al., Drosophila to be required for branching morphogenesis of the tracheal system (Jones et al., in vivo studies have demonstrated that the exocyst MTC is required for a range of functions associated with different tissues and organs.Exocyst is an octameric complex consisting of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70, and Exo84 which has been proposed to mediate tethering of transport carriers derived from the recycling endosomes and the Golgi for fusion with the plasma membrane (Grote et al., C. elegans and Drosophila and the identification of mutations in membrane tethers associated with disease in patients, have revealed a wide range of biological functions for membrane tethers in both the secretory and endocytic transport pathways. Defects in embryogenesis, tissue development, neural networks, and a range of tissue-specific disorders have been identified, particularly muscular-skeletal disease/dysfunctions. These findings demonstrate that the individual tethers are non-redundant factors essential for fundamental cell processes. Given the range of phenotypes associated with these genetic studies, and the differences in susceptibility of different cell types to knocking out or silencing individual tethers, it is likely that many membrane tethers have functions that extend beyond acting as a docking factor for vesicle fusion. Given their multiple binding partners, tethers are likely to co-ordinate a network of interactions which could regulate the establishment of membrane subdomains and the integrity of organelles.Genetic studies of membrane tethers in mice, Drosophila. More sophisticated approaches of conditional and inducible knockout systems would be particularly useful to explore the functions of tethers in individual tissues and organs in the adult, as illustrated by the recent studies of the exocyst in ureter function in the mouse (Fogelgren et al., Many mutations of tethering genes are embryonic lethal in mouse and in vivo now requires exploration of their binding partners in specific cell types. There may be binding partners of membrane tethers which are cell type specific and which are important for cell type specific functions. The application of a molecular systems biology approach to compare specialized cells from mutant and wild-type organisms should provide a deeper molecular understanding of the precise roles of membrane tethers in vivo. In particular, with the increasing awareness of the cross-talk that exists between different molecular pathways in the cell, it will be of interest to understand how the network of interactions mediated by tethers co-ordinate membrane trafficking and membrane flux in different specialized cell types. It is likely that this information will reveal fundamental insights into the relationship between membrane cell biology and physiological function.The molecular basis for many of the phenotypes described in this review are not clear and need to be further explored. The binding partners of membrane tethers have mostly been identified in cell lines which has provided an initial framework for defining their function; however, understanding the molecular basis of the cell and tissue-specific phenotypes of membrane tethers WHT and PG contributed to the writing of the review and the design of the figures.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The primary objective of present investigation is to introduce the novel aspect of thermophoresis in the mixed convective peristaltic transport of viscous nanofluid. Viscous dissipation and Joule heating are also taken into account. Problem is modeled using the lubrication approach. Resulting system of equations is solved numerically. Effects of sundry parameters on the velocity, temperature, concentration of nanoparticles and heat and mass transfer rates at the wall are studied through graphs. It is noted that the concentration of nanoparticles near the boundaries is enhanced for larger thermophoresis parameter. However reverse situation is observed for an increase in the value of Brownian motion parameter. Further, the mass transfer rate at the wall significantly decreases when Brownian motion parameter is assigned higher values. Mixed convection in vertical channels is of considerable importance for the enhancement of cooling systems in engineering. This includes modern heat exchangers, nuclear reactors, solar cells and many other electronic devices. Such flows are mainly affected by buoyancy. MHD mixed convective heat transfer analysis in vertical channels is of considerable importance due to its applications in self-cooled or separately cooled liquid metal blankets, cooling systems for electronic devices, solar energy collection and chemical processes. Use of nanoparticles as means to enhance the heat transfer in low thermal conductivity fluids has proven to be a novel technique Peristaltic pumping is a mechanism of the fluid transport in a flexible tube by a progressive wave of contraction or expansion from a region of lower pressure to higher pressure. Peristalsis is one of the major mechanisms for fluid transport in physiology. It is an involuntary and key mechanism that moves food through the digestive tract, bile from the gallbladder into the duodenum, transport of blood through the artery with mild stenosis, urine from the kidneys through the ureters into the bladder and sperm through male reproductive track. Further, several engineering appliances including roller and finger pumps, hose pumps, dialysis and heart-lung machines are designed on the principle of peristalsis. Subject to such extensive applications, several investigators studied peristaltic flows under different flow configurations It is noticed that none of the above mentioned studies and others in the existing literature investigate the novel aspect of peristaltic transport with the thermophoresis boundary condition. This study aims to fill this void. Therefore this article investigates the peristaltic transport of viscous nanofluid under the influence of constant applied magnetic field. Incompressible fluid is taken in a channel with thermophoresis condition at the boundaries Consider a viscous nanofluid in two-dimensional symmetric channel of width Here We define the following dimensionless quantities in order to non-dimensionalize the problemc = 2 cm/min, The assumptions of long wavelength and small Reynolds number give Here ough Eq. . the conough Eq.  and 15) denotes F as the dimensionless mean flows in the laboratory and wave frames byDefining Kuznetsov and Nield Thus the dimensionless boundary conditions in the present flow ared in Eq.  and The system of Eqs. –18 subjeThis portion of the article aims to analyze the numerical results through graphs. Plots for axial velocity, temperature and concentration are prepared and analyzed. Heat and mass transfer rates at the wall are studied through bar-charts.Nb>1. Temperature profile for variation in different parameters is studied through Impact of different parameters on the concentration of nanoparticles is examined through Effects of Hartman number, Brownian motion and thermophoresis parameters on the heat and mass transfer rates at the wall are studied through bar-charts given in In order to check the validity of the solution methodology and the obtained results, we provide the comparison of the special case of present study with the results of Ali et al. MHD mixed convective peristaltic transport of viscous nanofluid in a channel with thermophoresis at the boundaries is examined. Key findings of this study are summarized below.Thermal and concentration Grashoff numbers have opposite effects on the axial velocity and temperature of nanofluid.Axial velocity decreases with an increase in the value of Brownian motion parameter whereas opposite is reported for thermophoresis parameter.Temperature of the nanofluid decreases with increase in the strength of applied magnetic field and Brownian motion of nanoparticles.Increase in the strength of applied magnetic field results in an increase in nanoparticles concentration near the channel walls.The Brownian motion and thermophoresis parameters have large but opposite effects on the concentration of nanoparticles.Significant decrease in the mass transfer rate at the wall is noted when Brownian motion parameter is assigned higher values.


A 47 year-old male, with no history of pathological notables who present since 3 years chronic and severe itching eyelids pushing the patient to remove her eyelashes. Examination of the eyelids objectified a madarosis with irritation of eyelids (A). Dermoscopic examination revealed the presence of nits attached to the eyelashes (B). There was any lesions on the examination of other body areas. Based on the observation of nits at the base of the eyelashes (C) a diagnosis of phthiriasis palpebrarum was mad. Patient was treated with oral ivermectin associated to hygiene measure. Phthiriasis palpebrarum (lice infestation of eyelids), caused by the Phthirus pubis, is an unusual cause of blepharitis and conjunctivitis and may easily be overlooked because of the failure of physicians to recognize P. pubis. Dermoscopy can aid in the detection of nits and in monitoring treatment response by determining whether nits contain viable or dead nymphs or are empty (D).


The purpose of this research topic is to showcase recent anatomical, physiological, and clinical studies revealing how the cerebellum is embedded within distributed neural networks recruited during both direct motor functions plus cognitive and other domains. The topic comprises a total of 15 articles that together span experimental, theoretical, methodological approaches, and reviews of the literature.In recent decades, converging lines of evidence indicate that the roles of the cerebellum extend beyond direct motor control to include interactions with higher centers associated with cognition. Identifying the functional roles of the cerebellum within these wider brain networks is therefore of critical importance when developing methods to alleviate symptoms of both motor and non-motor disorders  will surely lead to important advances in our understanding of cerebellar roles in health and disease.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The adjustable microfluidic devices that have been developed for hydrodynamic-based fractionation of beads and cells are important for fast performance tunability through interaction of mechanical properties of particles in fluid flow and mechanically flexible microstructures. In this review, the research works reported on fabrication and testing of the tunable elastomeric microfluidic devices for applications such as separation, filtration, isolation, and trapping of single or bulk of microbeads or cells are discussed. Such microfluidic systems for rapid performance alteration are classified in two groups of bulk deformation of microdevices using external mechanical forces, and local deformation of microstructures using flexible membrane by pneumatic pressure. The main advantage of membrane-based tunable systems has been addressed to be the high capability of integration with other microdevice components. The stretchable devices based on bulk deformation of microstructures have in common advantage of simplicity in design and fabrication process. Effective fractionation of beads and cells in microfluidic devices is essential for applications such as lab-on-chip for pharmaceutical and biological studies ,2,3. FunThe active techniques of fractionation that are reported extensively for microfluidic applications are normally based on discrimination between different parameters of cells or beads due to the physics of motion in fields of acoustic , opticalThe methods of hydrodynamic-based passively differentiate between the label-free microparticles only by using their intrinsic properties of size, form, deformability, stiffness, and viscoelastic behavior ,25,26 inThe main feature of mechanically tunable separation systems is deformation of microstructures of a device under mechanical loads such as external forces of compress and stretch or internal pneumatic pressure for the purpose of influencing the interaction between microstructures and fluid flow of microbeads or cells. Until now, there are just a few microdevices that have been developed by implementing this concept for modification of selectivity of cells and beads. Meanwhile, the technique has been reported for similar microfluidic-based applications such as mechanically tunable optofluidic devices , mechaniIn this review, the focus is on a group of microfluidic devices that effectively have adjustability performance by using mechanical actuators for hydrodynamic-based fractionation of cells and beads. The small modulus of elasticity of elastomeric materials in addition to appropriate design of microstructures in hydrodynamic-based separation of beads and cells allow such devices to have a tunable selectivity . The motThe microfluidic devices in present review are classified according to flexibility in two groups of structural-based and membrane-based. The reviewed works, such as the tunable separation using pillar-based microfluidic ,40,41, tThe present paper is organized as follows. The effect of substrate type and loading techniques on deformation of microstructures in a microfluidic device is briefly reviewed in The forced deformation of microstructures in elastomeric microfluidic devices is an easy way of changing the width and height of microchannels in existing systems without repeating the costly fabrication process of a new design. Physically, when the microchannel dimensions are distorted under stress, the parameters of fluid flow such as pressure and velocity components that are important components of momentums of beads and cells are altered. The direction, frequency, and total amount of deformation of microstructures determine the amount of adaptation occurs to interaction between microbeads or cells with the fluid flow and the walls of modified microchannels . The intAll materials utilized in fabrication of microfluidic devices exhibit a level of elasticity under different loading intensities. Those with large modulus of elasticity such as silicon (E = 169 GPa) ,48,49 deThe size-based hydrodynamic manipulation of beads and cells in microfluidics devices has been achieved by adjustment of a critical geometry such as the width of narrow gaps in microstructures or the cross-section profile of the microchannel that stream of micro particles has to pass through it. The mechanical tuning with high resolution of the manipulation in such systems has been conducted by elastic modification of the critical dimensions of microstructure defined based on characteristic size of the microparticles. As shown schematically in 1 stretched to d2 by the force of F. The force is normal to the channel direction and uniformly distributed on the edges of device. This simple design has been implemented in tunable pillar-based system with uniform micron-scale spacing for size-based microfiltration on PUMA substrate [F is applied on the microchip by actuator clamped to the microdevice for stretching the length from L to L + ΔL. To have a micron precision tunability, actuating systems with high resolution have been used. The required external force in the device plane has been supplied by off-chip actuators that are either manually [In ubstrate  and tunaubstrate . The reqmanually  or autommanually  controll1d to 2d while the overall thickness of the elastomeric device is reduced by ΔT. The concept of adjustable devices has been exploited for elastomeric tuning of hydrophoretic separation [In paration . The forP, determines the effective deflection of the membrane with the thickness of t. Design and sizing of the microfluidic device is normally performed such that any unwanted deformation in microstructures is at lowest while displacement of membrane is maximum [Deflection of a thin membrane by pneumatic pressure is a well-known technique that has been implemented by several researchers for controlling the pneumatic and microfluidic zones in a microdevice for separation , isolati maximum ,46.The p maximum . The comSeveral design models have been introduced based on manipulation of microbeads or cells in interaction with fluidic flow and device internal microstructures ,61. In hPhysical manipulation of cells and beads by mechanical tuning of elastomeric microfluidic devices via bulk deformation of their microstructures has been implemented in different ways. As depicted schematically in The elastomeric microfluidic devices with pillar-based microstructures have been demonstrated as suitable candidates in tunability for separation of microbeads and cells. A microstructure layer consisted of an array of pillars is mechanically stretched to increase the inter-pillar spacings with micron or nano resolution. The limitation on tunability of the device is maximum force of actuator and stretchability of the substrate. The tuning is made before microfluidic injection and is reversible by the elastomeric material. The demonstrated advantage of such mechanisms has been the simplicity and low-cost fabrication process.θ and d, with resolution as low as 10 nm as depicted in The mechanically tunable device based on DLD technique as shown schematically in Another tunable system is a work of the authors of the present review on using linear arrays of pillars with square cross-section for microfiltration of blood cells and beads . The sepThe microfluidic devices consisted of array of cup-shaped elements as shown in The hydrophoretic continuous separation of bulk of microparticles has been adapted tunable by Park’s group using elastic deformation of the microchannel cross-section . The oriMechanical tuning of microfluidic devices for the purpose of manipulation of beads and cells by technique of local deformation of thin membranes under pulsing pneumatic pressures or controlled by valve has been exploited by several researchers. A number of such novel devices have been introduced with PDMS membrane as the core element or for actuation of a microstructure for handling , trappinet al. for microfiltration using tunable blockage of a microchannel cross-section [A microdevice has been reported by Huang -section . The devAnother filtration mechanism consisted of resettable traps for cells and beads with selectivity based on size and deformability has been introduced recently by Ma’s group . The iniAdditionally, a microfluidic device has been introduced for enhancement of separation efficiency in a straight microchannel integrated with membrane. Air bubble plugs are incorporated for formation of a wide and uniform slit. The membrane with thickness of 50 µm is actuated by pneumatic pressures of 50–80 kPa in a three-layer device [A microfluidic system has been introduced for size-based separation of microbeads and blood cells by Lee’s group that works using membrane deflection as the actuating element for a floating block structure . The criet al. using array of dynamic U-shaped microstructures [Recently, a microfluidic device has been developed for trapping of controllable number of cells by Liu ructures . One of ructures . As showSo far, several elastomeric microfluidic devices have been designed and fabricated with mechanical tunability for size-based fractionation of cells and beads with applications defined in biological studies and other research fields. Tunability of the described systems enables us to adjust and to optimize the performance and efficiency of operation in microscale for the working conditions suitable for each specific application. In The microfluidic systems that are adapted tunable using existing methods such as DLD , pillar-The two methods of stretchable and dynamic cup-shape structures that work base on modified forms of fixed U-shape posts for cell trapping, demonstrate the importance of novel ideas in development of alternative devices with similar applications and general performances but with more flexibility and compatibility with other microfluidic components.The membrane-based tunable devices are designed with clog-free mechanism, which is very important for continuous working and integration with other microfluidic components such as micropumps and valves for applications in more complex systems and lab-chip devices. These types of microfluidic systems have more creative designs for tunability compared to other devices. The materials and processes necessary for development of these devices are typical in microfluidic technology.All reviewed tunable hydrodynamic-based microfluidic devices are potentially applicable for separation of solid microbeads and deformable biological cells. This review article provides a good reference for investigation of the microfluidic platforms with purely mechanical tunability and the corresponding limitations and possibility of further development and enhancement.


The cochlear nucleus (CN) is the first processing center of auditory signals from the cochlea. Several distinct neuronal circuits have been identified that form different parallel representations of auditory information from auditory nerve fibers (ANFs). One cell circuit of interest is the stellate cell microcircuit of the ventral cochlear nucleus (VCN), which is centered on two populations of stellate cells, known as T and D stellate cells . The outA neural network model of the stellate microcircuit was created using leaky integrate-and-fire neurons for each cell in the network. The key mechanisms incorporated to achieve SNR and dynamic range improvement were wide-band lateral inhibition and selective processing of excitatory and inhibitory inputs . The numTo quantify the enhancement achieved by the network, two signal-to-noise metrics were used. SNR metric 1 measures the level of noise reduction and is calculated as the ratio of the average output rate of cells within 1.5 critical bands of the known stimulus frequency to the average background output rate. SNR metric 2 measures the level of peak enhancement and is calculated as the ratio of the maximum output rate of the cells within 1.5 critical bands of the known stimulus frequency to the maximum background output rate. The metrics were calculated for the input signal, the input ANF population, and the TS cell population. Each metric was calculated for the first three formants of the vowel /o:/ and for a range of input SNR values. The SNR metric 1 was significantly higher than for the ANF population for the majority of input SNR levels. Similarly, SNR metric 2 was also higher for the TS cell population than for the ANF population. This demonstrates that the TS cells improved the ability to decode the spectral information in noise and the model illustrates the mechanisms by which this is achieved.


The homophilic potential emerges as an important biological principle to boost the potency of immunoglobulins. Since homophilic antibodies in human and mouse sera exist prior environmental exposure, they are part of the natural antibody repertoire. Nevertheless, hemophilic properties are also identified in induced antibody repertoire. The use of homophilicity of antibodies in the adaptive immunity signifies an archetypic antibody structure. The unique feature of homophilicity in the antibody repertoire also highlights an important mechanism to boost the antibody potency to protect against infection and atherosclerosis as well to treat cancer patients. PepWorking with homophilic-converted Trastuzumab (Herceptin), we discovered that the dose–response in inducing apoptosis in a Her2/neu-expressing human cell line was not linear but was bell shaped . The higThis non-linear dose affecting the potency of homophilic Herceptin could be due to the inherent mechanic of self-binding that was observed in 1986 , 55. HerWe believe that we are only at the beginning to discover networks of shared idiotypes. By using polyclonal anti-idiotype antibodies, Urbain and colleagues have observed shared idiotypes expressed on antibodies with different antigen specificity in rabbits and mice , 56. TheThe data on homophilic natural antibodies point to a general strategy of enhancing potency not only of antibodies but also other biological systems . This fiThe homophilic antibody enhancement and therapeutic potential have been already demonstrated , 46. TheThe discussion of the unique feature of homophilicity as a part of the natural and induced antibody repertoires  highlighHK surveyed the literature and wrote the article. JB and SK provided suggestions. All authors approved the final version of this article for publication and accepted the responsibility for the integrity of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The National Health Security Scheme was established 10 years ago with the document finance model in communicating the transfer of budget from payer to providers. This model was found to be inefficient in transferring (17 billion Baht delay) or not knowing the amount transferred (33 billion Baht bad debt). A new ageing account model was developed 3 years ago to improve efficiency in financial process. It is interesting to know whether the change achieved the efficiency. This research also wanted to compare efficiency in financial process of all three government health insurance funds managed by the National Security Health Office , the Social Security Office (SSO managing insurance for workers in private sector) and the Comptroller General Department (CGD managing insurance for civil servants and dependents).This research employed two rounds of questionnaire surveys to heads of finance department in hospitals in 2010 and 2012. An in-depth interview was employed in ten of responses from the Ministry of Public Health hospitals commenting that the new model achieved the most efficient financial process and another ten complaining the least efficient process. Eight hospitals outside the MOPH were added to get unbiased views comparing financial processes of the three government health insurance funds. The interviews were undertaken from November 2012 to February 2013.Comparing results from the two surveys: providers felt a marginal increase in financial process of the ageing account model in terms of efficient transfer, outstanding realisation, speed and the ease of use of transferred fund. The new model was inferior to the old model in terms of the frequency of sending financial report. Qualitative data confirmed that efficiency was interpreted as the quickness and correctness of fund transfer. The better efficient responders explained that the NHSO transferred fund became quicker and simpler to use. However, the least efficient responders explained that the CGD transferred fund quicker than the NHSO and used web-based financial report for quickness and transparency. The accounting items of the NHSO were the most difficult to understand.With perceived marginal increase in efficiency of the new account model, the NHSO should improve timeliness and comprehensiveness of the account model as a benchmark with other two government health insurance funds.


Wireless Sensor Network monitor and control the physical world via large number of small, low-priced sensor nodes. Existing method on Wireless Sensor Network (WSN) presented sensed data communication through continuous data collection resulting in higher delay and energy consumption. To conquer the routing issue and reduce energy drain rate, Bayes Node Energy and Polynomial Distribution (BNEPD) technique is introduced with energy aware routing in the wireless sensor network. The Bayes Node Energy Distribution initially distributes the sensor nodes that detect an object of similar event  into specific regions with the application of Bayes rule. The object detection of similar events is accomplished based on the bayes probabilities and is sent to the sink node resulting in minimizing the energy consumption. Next, the Polynomial Regression Function is applied to the target object of similar events considered for different sensors are combined. They are based on the minimum and maximum value of object events and are transferred to the sink node. Finally, the Poly Distribute algorithm effectively distributes the sensor nodes. The energy efficient routing path for each sensor nodes are created by data aggregation at the sink based on polynomial regression function which reduces the energy drain rate with minimum communication overhead. Experimental performance is evaluated using Dodgers Loop Sensor Data Set from UCI repository. Simulation results show that the proposed distribution algorithm significantly reduce the node energy drain rate and ensure fairness among different users reducing the communication overhead. The major task of wireless sensor network (WSN) is intermittent monitoring of environment, where data or objects are sensed and then sent to the base or sink node for further processing. With the increasing demand in the network, the design of sensor nodes should be performed in such a manner with high-density operation with minimum transmission bandwidth. Therefore, the objective of minimizing network traffic has become an important issue.Data Routing for In Network Aggregation (DRINA) for WSNs  resultedThe integrated Wireless Hospital Sensor Network  maximizeA new constructing approach for a weighted topology of wireless sensor networks (WSNs) is designed in  based onA scalable and energy efficient mechanism is designed in  to improIn wireless sensor networks, each sensor nodes compete with each other in order to access the shared transmission medium. With increasing traffic in the network, proper routing protocols have to be designed due to the higher level of interference. Energy efficient method using energy balanced routing protocol is based on forward aware factor technique introduced in . In FAF,Maximum Weighted Matching (MWM) scheduling algorithm was designed in  to improAmong the various measurements the graph invariants have been utilized for the structure of entropy-based measures to describe the structure of complex networks in . The ShaThis paper makes the following contributions: First, we present a Bayes Node Energy Distribution (BNED) model, which provides sink node an accurate subset of nodes by detecting target objects of similar events in an energy efficient manner reducing the energy consumption of sensor nodes. Second, we show that the major component of our BNEPD technique uses Polynomial Regression Function (PRF) to reduce node energy drain rate using polynomial coefficient. Therefore, the proposed BNEPD technique effectively integrates multiple functionalities like minimizing energy consumption, node energy drain rate with low time complexity. The performance of BNEPD technique compared with other possible data aggregations techniques is also investigated.The rest of this paper is organized as follows: Section 2 introduces several routing mechanisms adopted in wireless sensor network. The core component of our technique called BNEPD technique and the design goals of it is included in Section 3. Section 4 includes the experimental setup with parametric definitions. Section 5 discusses in detail the results using table and graph form. Section 6 finally concludes with the concluding remarks.Wireless Sensor Networks are equipped with different communication and computing capabilities and hence applicable to different operating scenarios. Hence routing protocol for relay node placement is one of the most important to be performed in WSNs involving diversified environments. In , approxiDefending collaborative false data injection attacks in wireless sensor networks designed in  combine One of the most important functionality considered in wireless sensor network is the link scheduling. This is because of the shared and wireless nature of the network that changes drastically over time. Wireless scheduling algorithms  used strActive node and dynamic time slot allocation was introduced in  with theWireless sensor network has been introduced for several reasons including securing the link to physical humanity, excellent robustness and capability to work; hence is employed for wide range of applications. In various WSN applications, motion strength has a common view of monitoring the field. Most of the existing researches on movement monitoring focused on dealing with single object, where object numeration was not required. Sensor nodes are used for sensing the node emitted by an object such as, sound, vibration, etc., to detect the appearance of an object, and then helps to monitor and track it.The proposed technique is employed to distribute the sensor nodes and identifies energy efficient routing path of similar event using Bayes Node Energy Distribution and Polynomial Regression Function in Wireless Sensor Network. The distribution of sensor nodes is performed through Bayes distribution that detects an object of similar event. The energy efficient routing path for each sensor nodes are generated by data aggregation at the sink based on polynomial regression function. We use a novel distribution algorithm to adaptively represent nodes stop sensing and transmitting data to sink for a specific time period. The framework of the Bayes Node Energy Polynomial Distribution technique is shown in The framework of BNEPD technique is divided into construction of Bayes Node Energy Distribution, applying Polynomial Regression Function for data aggregation and application of Poly Distribute algorithm. The framework starts with the construction of Bayes Node Energy Distribution that applies Bayes rule through which the sensor nodes senses the target object of similar events  within its frequency to reduce the consumption of energy.Next, the Polynomial Regression Function is applied to the target object of similar events for multiple sensors and are aggregated on the basis of the minimum and maximum object of events, sent to the sink node. Finally, the Poly Distribute algorithm distribute the sensor nodes in an efficient manner that splits the nodes to be in sleep state and nodes for object detection of similar events according to the number of nodes in the network and network size. The elaborate description of design of BNEPD technique is explained in the forthcoming sections.In this section, a decentralized approach using Bayes principles is presented in order to increase the performance of the network. Instead of compressing data collected by the sensor nodes in Wireless Sensor Network, the BNEPD technique selects subset of the nodes  in the network that detects an object of similar event and transmits the data to the sink node.Whenever an additional sensor node has to be included in the network using conventional types of network, though results in increasing only a small portion of accuracy in the sensing file, due to highly correlated nature of the sensed data, but compromises the energy consumption level.On the other hand, the BNEPD technique distributes the sensor nodes that detect an object of similar event  into specific regions using Bayes principle which identifies minimal energy for sensed data being routed. G = , then V denotes the set of all sensor nodes and E denotes the set of all communication stations connecting all sensor nodes in WSN. With this principle, the problem of routing is defined as the process of detection of object of similar event initiated at the source node and finally ending at all the destination nodes, based on the network frequency. This routing path detection of similar event is in the form a spanning tree Tree =  which includes the source sensor nodes and all target object nodes for which it is specifically made.Let us consider the problem of routing using Bayes Node Energy Distribution and Polynomial Regression Function in Wireless Sensor Network in terms of a graph. If Bayes principle using BNEPD technique makes probabilities for each sensor node with the aid of probability models of corresponding frequency for which it is specifically made . In order to accomplish this, Bayes’ principle is used as a hypothesis for adjusting the degrees of belief  given the observed evidence .The Bayes principle in BNEPT technique obtains the probabilities of object detection of similar events. Then, the conditional probability concerning similar events is evaluated. The evaluated similar events are then sent to the sink node for further processing. The proposed Bayes principle for node energy distribution is then given as followsSN1 and TO2 are the sensor node and target object nodes respectively. Let Disti denotes the distance between the source and the target object nodes in WSN. Then the distance between SN1 and TO2 are measured as given below:From , SN1 anBased on the distance measurement given from , sensor Upon successful completion of identification of objects of similar events by sensor nodes and sending it to the sink node, the task of sink node for data aggregation comes into action. The aggregation of data in BNEPD technique involves the process of collection and aggregation of similar events. With the objective of reducing the energy drain rate, data aggregation using polynomial regression function is used in the proposed work to save the limited resources through which the network lifetime is also increased and maintain high energy nodes in the routing path.Data Aggregation using Polynomial Regression Function (DAPRF) in BNEPD technique represents the sensed objects in the form of polynomial functions. The idea behind BNEPD technique is that DAPRF performs aggregation of data with the aid of polynomial coefficients that represent sensor object.Many sensor nodes send their objects  to the sink node. The sink node, on receiving the objects from multiple sensor nodes, then uses the Polynomial Regression Function to obtain the coefficient values of regression for each object. As a result, separate coefficient values are obtained for pressure, temperature and so on. The Polynomial Regression Function applied in BNEPD technique is given as belowa, and b objects of similar events are calculated. The five regression values are then sent to the sink node, as well as the frequency of the objects of similar events for which the polynomial coefficients are evaluated. The sink node now has the following two sets of data  on receiving the coefficients from its target object of similar events:Thus the minimum and maximum value of i’ th and ‘i + 1’ th value include the sum of polynomial coefficient of first object, coordinate range of first object of similar event, sum of polynomial coefficient of second object and finally the coordinate range of second object of similar event respectively.From  and 5),,5), the The advantage of BNEPD technique is that the target object sends the polynomial coefficient obtained through polynomial regression function instead of sending the entire objects of similar events to the higher level. When a new target object is detected, an updated regression polynomial function is evaluated at higher level using polynomial coefficients sent by the objects of similar events and values obtained from the source object. As the BNEPD technique only sends the polynomial coefficient value, energy savings take place and therefore energy drain rate is reduced improving the performance of the entire network.Finally, a novel distribution algorithm called Poly Distribute is designed to reduce the communication overhead. The Poly Distribute algorithm is distributed in such a way that it helps in the data aggregation improvement in BNEPD by designing the network in such a way that certain sensor nodes stop sensing and transmitting the data to the sink node for a time period. Finally, using Poly Distribute algorithm in BNEPD technique, the sink node uses Bayes principle on the object which it has received for the entire network. The algorithmic description of Poly Distribute applied in BNEPD technique is given belowConstruction of Poly Distribute algorithmStep 1: Determine the number of nodes to sense the target object of similar eventStep 2: Determine the number of nodes to be in sleep stateStep 3: BeginStep 4: RepeatStep 5: Detection of target objects by sensor nodes of similar eventStep 5.1: Apply Bayes principleStep 5.2: Send objects of similar events to sinkStep 6: Perform data aggregation Step 6.1: Apply polynomial regression function Step 6.2: Send minimumand maximum value objects of similar events Step 6.3: Evaluate polynomial coefficientStep 7: Until Step 8: EndThe above algorithm I shows the construction of poly distribute algorithm which performs three important steps. The first step involved in poly distribute algorithm is the selection of nodes. In this step, the number of nodes to be in the sleep state and the senor nodes to sense the target object of similar event is determined in a random manner. The random selection is designed on the basis of the number of nodes in the network and based on the remaining energy of each sensor nodes.The second step is to detect the target object of similar events by the sensor nodes through Bayes principle based on the probability of events and distance function to the sink node. Finally, the sink node performs the data aggregation using polynomial regression function that determines the minimum and maximum value objects of similar events through polynomial coefficient. The above said process is repeated for all objects in the network. In this way, the communication overhead is reduced.In this section, we evaluate the proposed BNEPD technique and compare its performance to two other known data aggregation: Data Routing for In Network Aggregation (DRINA) for WSNs  and CellSimulations were carried out in an extensive manner with random number for 70 iterations. To illustrate the simulation results for BNEPD technique, 350 sensor nodes were used with energy of each sensor node being 5 J, network size of 1000 * 1000 m with a transmission range of 100 m. We evaluate the BNEPD technique performance under the following metrics: Energy consumption, Energy drain rate, Communication overhead and time complexity.Energy consumption using BNEPD technique is the product of sensor nodes, power (in terms of watts) and time (in terms of seconds). The energy consumption is measured in terms of Joules (J). The mathematical formulation for energy consumption using BNEPD technique is given as belowThe energy drain rate for BNEPD technique is measured using exponential weighted moving average that represents the previous and newly calculated values. It is measured in terms of joules (J). The mathematical formulation for energy drain rate is given as belowThe communication overhead generated using BNEPD technique is the ratio of difference between actual communication time  and computed communication time to actual communication time. It is measured in terms of milliseconds (ms). The mathematical formulation for communication overhead is given as belowTime complexity using BNEPD technique is the time taken to sense the data or object of corresponding frequency. It is measured in terms of milliseconds (ms).In this section, simulation results are presented to evaluate the energy aware routing in wireless sensor network and to demonstrate the performance of the proposed distribution algorithm. In order to analyze the characteristics and functionality of the BNEPD technique, we quantitatively accessed the performance with the network size of 1000 * 1000 measured at 100 to 800 (m/s) using Dynamic Source Routing (DSR) Protocol by comparing the outcomes, the results achieved with the Poly Distribute algorithm. The Bayes Node Energy Polynomial Distribution (BNEPD) technique is compared against the existing Data Routing for In Network Aggregation (DRINA) for WSNs . The expTo support transient performance, in The mathematical evaluation for energy consumption using BNEPD, DRINA and CBPS is given below. It is the product of number of sensor nodes, power consumed and time taken using three methods.The Energy drain rate of our BNEPD technique is presented in The mathematical evaluation for energy drain rate using BNEPD, DRINA and CBPS is given below. It is the product of number of sensor node, old energy and new energy drain rate respectively.Mathematical evaluation for communication overhead using BNEPD, DRINA and CBPS is given below. It is the difference between the actual communication time  and computed communication time . The communication overhead obtained using four methods are as given below.The targeting results of communication overhead using BNEPD technique with two state-of-the-art methods ,2,12] i i12] in In Mathematical evaluation for time complexity using BNEPD, DRINA and CBPS is given below. It is the time taken to perform the communication overhead for different number of sensor nodes. The time complexity using three methods are as given below.To explore the influence of time complexity on BNEPD technique, simulations are performed by applying 350 different sensors with a network size of 1000 * 1000 m in a transmission range of 100 ms depicted in We have proposed a new Bayes Node Energy Polynomial Distribution (BNEPD) technique to solve the issues related to routing and reduce energy drain rate with energy aware routing in Wireless Sensor Network. The energy aware routing in Wireless Sensor Network has been formulated as a Bayes Node Energy Distribution problem and solved through a novel probability method of object detection of similar events using novel Poly Distribute algorithms. The obtained results demonstrate better performance of objects of similar event detection and minimal energy for sensed data being routed over a number of sensor nodes. Our results also show that with the application of Bayes principle, node energy consumption is extensively reduced that effectively detects object of similar event and transmit the data to the sink node. Furthermore, the experimental part indicates that by applying polynomial regression function, the proposed BNEPD technique, converges minimized communication overhead based on the novel Poly Distribute algorithm that stops stop sensing and transmitting the data to the sink node for a time period. The performance of BNEPD technique is compared to other known data aggregation techniques. The performance of BNEPD technique was compared with different system parameters, and evaluated the performance in terms of different metrics, such as energy consumption, energy drain rate, time complexity and communication overhead. The results show that BNEPD technique offers comparatively better performance than the other techniques in all of the scenarios considered.In the forthcoming research work, the proposed energy control for distributed estimation in wireless sensor networks needs to be expanding the wide range of network that uses more number of sensor nodes. This enables data to be stored and processed by devices with more resources.S1 File(PDF)Click here for additional data file.