A regional-scale sensitivity study has been carried out to investigate the climatic effects of forest cover change in Europe. Applying REMO , the projected temperature and precipitation tendencies have been analysed for summer, based on the results of the A2 IPCC-SRES emission scenario simulation. For the end of the 21st century it has been studied, whether the assumed forest cover increase could reduce the effects of the greenhouse gas concentration change.Based on the simulation results, biogeophysical effects of the hypothetic potential afforestation may lead to cooler and moister conditions during summer in most parts of the temperate zone. The largest relative effects of forest cover increase can be expected in northern Germany, Poland and Ukraine, which is 15–20% of the climate change signal for temperature and more than 50% for precipitation. In northern Germany and France, potential afforestation may enhance the effects of emission change, resulting in more severe heavy precipitation events. The probability of dry days and warm temperature extremes would decrease.Large contiguous forest blocks can have distinctive biogeophysical effect on the climate on regional and local scale. In certain regions of the temperate zone, climate change signal due to greenhouse gas emission can be reduced by afforestation due to the dominant evaporative cooling effect during summer. Results of this case study with a hypothetical land cover change can contribute to the assessment of the role of forests in adapting to climate change. Thus they can build an important basis of the future forest policy. Climate change and its impacts on different spatial and temporal scales and sectors have been addressed by several international research projects in the last decade-3. All rThe considerable enhancement of inter-annual variability of the European summer climate as well as the changes of the hydrological cycle can lead to higher probability of extremes compared to present-day conditions,6-11. ThClimate change affects the key sectors such as hydrological systems, infrastructure, human health, agriculture and forestry. Changes of the climatic means and extremes already show impacts on land cover that are expected to be more severe under future climate conditions. Drought periods and other extremes are responsible for a significant share of agricultural losses in Europe. Impacts of severe droughts on the composition, structure, and biogeography of forests have been detected worldwide in the recent decades,18. On t2 concentration[2 warming of deforestation can dominate over albedo cooling effect . Several studies have addressed the biogeophysical cooling and moistening effect of tropical forests[Land cover in turn interacts with the atmosphere, thus it has an important role in climate regulation. Vegetation affects the physical characteristics of the land surface , which control the surface energy fluxes and hydrological cycle. Through biogeochemical processes, ecosystems alter the biogeochemical cycles and thereby changing the chemical composition of the atmosphere-27. Depentration,29,30. Pntration. Dependi forests. Whereas forests-34. Clim forests,36 and m forests. In Cana forests,39. Thes forests, as wellEurope is the only continent with a significant increase of forest cover in recent times. In the last two decades the annual area of natural forestation and forest planting amounted to an average of 0.78 million hectares/year. Land us• the biogeophysical effects of a hypothetic potential afforestation on summertime temperatures and precipitations, for the end of the 21st century and its regional differences within Europe,• the magnitude of the biogeophysical feedbacks of forest cover increase compared to the projected climate change signal with special focus on the probability and severity of temperature and precipitation extremes.This subsection summarizes the most important aspects that are essential for the appropriate interpretation of the results. The experimental set-up and the method of the analyses are introduced in Sect. 4 more in detail.In order to provide climate change information due to emission change, an emission scenario simulation for the future 2071–2090) and a reference simulation for the past (1971–1990) has been carried out applying the regional climate model REMO,43. Both–2090 andFirst, the sign and magnitude of the climate change signals without any land cover change have been investigated comparing the summer temperature means and precipitation sums in the time period 2071–2090 to 1971–1990. Increase of temperature is projected to occur with precipitation decrease in Southern- and Central-Europe and in the southern part of Scandinavia, whereas Northeast-Europe can be characterized with warmer and wetter conditions Figure . In agreSecond, climate change signal due to potential afforestation has been determined comparing the simulation results with- and without forest cover increase for 2071–2090. The regions have been identified, where the hypothetic forest cover increase shows the largest effects on summer temperature and precipitation Figure . Land coConsequently, the regions characterized by largest climatic effects of afforestation do not correspond to the areas with the largest signals due to emission change. The magnitude of the climatic effects of both emission change and potential afforestation differs among regions. In most parts of the temperate zone the cooling and moistening effects of afforestation are dominant during summer. These feedbacks can reduce the projected warming and drying especially in the northern part of Central-Europe and Ukraine. Whereas increase of the forest cover can enhance the climate change signal for precipitation in some part of Spain, Belarus and Russia but the magnitude of this impact is relatively small compared to the effect of the emission changes. Thus the analysis of the magnitude of the climatic feedbacks of afforestation relative to the effects of the enhanced greenhouse gas emission can help to determine the regions, where forests can play an important role in altering the climate change signal.The regional characteristics of the effect of the assumed potential afforestation on temperature and precipitation have been analysed for three selected regions  would be larger than its decrease due to the enhanced greenhouse gas emission Figure . Thus thIn the region of Northern France, the precipitation decrease based on the A2 emission scenario is projected to be larger −26%; -69 mm). If emission changes occurred together with potential afforestation, the half of the original climate change signal could be relieved  of temperature show that distributions of the daily temperature means are shifted towards the warmer direction under future climate conditions Figure . The PDFIn each of the selected regions the total number of warm extremes  are projected to increase significantly at the end of the 21st century  and an increase of the summer precipitation sum (up to 50–60 mm).• For precipitation, the climate change mitigating effects of afforestation differs among the selected regions. In the northern part of Germany the increase of forest cover would fully compensate the projected climate change signal. In Northern France the precipitation decrease based on the A2 emission scenario is projected to be larger than in Northern Ukraine. In both regions the half of the climate change signal could still be relieved assuming potential afforestation.• In each of the selected regions increase of forest cover may contribute to the decrease of the variability of the daily temperature means, thereby to the reduction of the projected climate change signal. The strong increase of the number of warm extremes  due to emission change can be slightly reduced by the assumed potential afforestation.• In Northern Germany and France, the forest cover increase would enhance the effects of emission change on extreme precipitation, resulting in more severe heavy precipitation events. The probability of dry days would decrease.The magnitude of the possible climate change reducing effects of a potential afforestation for Europe, on regional scale, for longer future time period have not assessed before. Based on the simulation results it can be concluded that large, contiguous forest blocks can have distinctive biogeophysical effect on the climate on regional and local scale. Our land cover change study confirm that in smaller areas the biogeophysical feedback processes can significantly affect and modify the weather and climate, the temperature and precipitation variability,46. The For the introduced sensitivity study, one regional climate model has been applied driven by one emission scenario. Multimodel ensembles and intercomparison studies are needed for studying the robustness of the results, which is the aim of recent EU-projects . The sp2 concentrations can also lead to the increase of the stomatal resistance thereby to the inhibition of the transpiration, which can amplify the global warming[Our sensitivity study focused on the biogeophysical feedbacks, the biogeochemical interactions, the processes related to the carbon sequestration of forests and soil were not taken into account. In the temperate zone, net climatic effects of forests are determined by various contrasting feedbacks. In case warming,52. TherFrom a practical point of view, results of this case study related to the investigation of the climate sensitivity due to a hypothetic land use change and its regional differences can contribute to the future adaptation strategies in European agriculture and forestry. The understanding of the role of land cover in the climate system becomes even more important. Land cover characteristics due to climatic conditions as well as policy induced land management are region-specific. The sign and magnitude of the climatic effects of afforestation and emission change also shows large spatial differences. Therefore, to obtain regional scale information, similar fine scale case studies are essential to quantify and predict the climatic effectiveness of the different land cover and land use practices.REMO  is aThe simulations have been carried out for Europe Figure , with 0.The following experiments have been performed and analysed Table :Reference simulation for the past (1971–1990) with present (unchanged) forest cover.• Emission scenario simulation for the future (2071–2090) with unchanged forest cover applying the A2 IPCC-SRES emission scenario . This eEmission scenario simulation with potential afforestation for 2071–2090. The potential afforestation map  have been recalculated and reaggregated for all model grid cells. Figure The analyses of the simulation results focused on the summer months , because of the high radiation input, intense heat and mass exchange. The leaf area index of the deciduous forests reaches its maximum in this period, which has a strong control on the land-atmosphere interactions.The sign and the magnitude of the temperature and precipitation changes have been analysed for the following three cases:• Climate change due to emission change has been investigated comparing the results of the simulations with unchanged land cover for 2071–2090 to 1971–1990.• Climate change due to potential afforestation have been calculated comparing the simulation results with- and without forest cover increase for the future time period (2071–2090).• Climate change due to emission change and potential afforestation has been determined comparing the results of the potential afforestation experiment (2071–2090) to the reference study in the past (1971–1990) without land cover change.2).A Mann–Whitney U-Test was applThe probability distribution of temperature has been calculated from the daily mean values in the investigated 20-year time periods based on the normal distribution function. The indices of temperature and precipitation extremes in this study were selected from the list of climate change indices recommended by the World Meteorological Organization–Commission for Climatology (WMO–CCL) and the Research Programme on Climate Variability and Predictability (CLIVAR). The seThe authors declare that they have no competing interests.BG carried out the simulations, analyzed and interpreted the results and drafted the manuscript. GK provided the forest cover database and map for the potential afforestation case study. KS and CT provided expertise and guidance during the simulations. AH contributed to the statistical analysis and to the interpretation of the results. DR and SH participated in the design of the study and have been involved in the discussion of the results and the critical revision of the manuscript. DJ coordinated the research, participated in the design of the study and has given final approval of the version to be published. All authors read and approved the final manuscript.


Dorsal dislocation of the intermediate cuneiform and isolated medial cuneiform fracturesare rare injuries. In this report, we present a patient who sustained a dislocation of theintermediate cuneiform and describe predisposing factors and the treatment procedure. Dorsal dislocation of the intermediate cuneiform is a rare injury, and only a few cases have been reported –3. The iA 30-year-old woman sustained an injury to her right foot when she was walking in high-heeled shoes and fell down the stairs with her foot in an equinus and inversion position. The patient complained of severe pain and was unable to bear weight in her right foot. The initial clinical examination of her foot revealed swelling and tenderness at the dorsum of the midfoot without an open wound. There was no vascular compromise, and sensation was preserved. Plain radiographs showed dorsal dislocation of the intermediate cuneiform bone and a nondisplaced fracture at the medial cuneiform . A compuThe three cuneiforms are wedge shaped and sit in the middle of the medial column of the foot. They are part of the transverse and medial longitudinal arches of the foot. The intermediate cuneiform is the smallest. Each cuneiform articulates with one third of the distal navicula proximally and its respective metatarsal distally . The staIsolated intermediate cuneiform dislocation was first described by Clark and Quint in 1933 . BecauseIn this case, closed reduction under general anesthesia failed, and we had to reduce openly. Five of the 6 reported cases with intermediate cuneiform dislocation were treated by open reduction , 2. Alth


The sphenoid sinus occupies a central location in transsphenoidal surgery (TSS). It is important to identify relevant anatomical landmarks to enter the sphenoid sinus and sellar region properly. The aim of this study was to identify anatomical landmarks and their value in single-nostril endonasal TSS. A retrospective study was performed to review 148 cases of single-nostril endonasal TSS for pituitary lesions. The structure of the nasal cavities and sphenoid sinus, the position of apertures of the sphenoid sinus and relevant arteries and the morphological characteristics of the anterior wall of the sphenoid sinus and sellar floor were observed and recorded. The important anatomical landmarks included the mucosal aperture of the sphenoid sinus, a blunt longitudinal prominence on the posterior nasal septum, the osseocartilaginous junction of the nasal septum, the ‘bow sign’ of the anterior wall of the sphenoid sinus, the osseous aperture and its relationship with the nutrient arteries, the bulge of the sellar floor and the carotid protuberance. These landmarks outlined a clear route to the sella turcica with an optimal view and lesser tissue damage. Although morphological variation may exist, the position of these landmarks was generally consistent. Locating the sphenoid sinus aperture is the gold standard to direct the surgical route of TSS. The ‘bow sign’ and the sellar bulge are critical landmarks for accurate entry into the sphenoid sinus and sella fossa, respectively. The pituitary gland is located below the center of the brain and over the sella on the cerebral surface of the body of the sphenoid. The sphenoid contains two sinuses, which open into the roof of the nasal cavity via the apertures on the posterior wall of the sphenoethmoidal recess directly above the turbinates. Since only thin layers of bone separate the sphenoid sinuses from the nasal cavities below and the sella turcica above, transsphenoidal surgery (TSS) is the first choice option for the removal of pituitary lesions rather than the transcranial approach.The transsphenoidal approach has evolved considerably since it was first successfully performed by Schloffer in 1907 . Since tHowever, the surgical path of TSS is extremely deep and narrow, and the view is usually blocked by crucial neurovascular structures. In addition, the close proximity of the sphenoid sinus to the carotid artery and the optic canal, plus the high levels of variation between the anatomical structures of the sphenoid sinus and sellar floor, make the approach even more difficult, hence the success of the treatment greatly relies on the experience of the surgeon and the familiarity with anatomical landmarks through the surgical route. To date, the methods and techniques of TSS adopted by different surgeons with respect to surgical guidance and important landmarks vary significantly. Our knowledge regarding the anatomical structures relevant to TSS is mainly based on postmortem or imaging studies –13. HoweThis study retrospectively reviewed 148 surgical records of single-nostril endonasal TSS for sellar lesions performed in our department in the period between May 2002 and February 2008. The patients included 78 males and 70 females with a mean age of 39.2 years . Preoperative magnetic resonance imaging (MRI) was performed for all patients to assess variations of the sphenoid bone, sphenoid sinus and sellar floor. Postoperative histopathological examination confirmed the diagnosis of pituitary lesions. The study was approved by the ethics committee of Fuzhou General Hospital . Written informed consent was obtained from all participants.Patients lay in the supine position with the head extended by 20°. Surgeons were positioned directly behind the patient’s head. The microscope was orientated perpendicularly to the surface of the surgical floor first and then later adjusted towards the mucosal aperture of the sphenoid sinus. All surgeries were performed via a unilateral endonasal transsphenoidal approach . This roAn endoscope was used in 26 patients to examine and identify the nasal structures and the mucosal aperture of the sphenoid sinus. Under an operating microscope, the sphenoid sinus was approached either by expanding the aperture or by incising the ipsilateral mucoperiosteum at the posterior third of the nasal septum, fracturing the vomer and separating the bilateral mucoperiosteum to finally expose the anterior wall of the sphenoid sinus, followed by an anterior sphenoidotomy. The sphenoid septum was then excised, the orientation of the sellar floor was determined and the bony sellar floor and dura were opened to approach the pituitary gland and lesion. After removing the pituitary lesion, the dural defect of the sellar floor was closed with a small piece of autologous muscle harvested from the thigh and coated with fibrin glue. In a few difficult cases, neuronavigation was employed to guide access to the sella turcica.In another 63 patients, the surgical procedure was similar to method A. However, the mucoperiosteal incision was made on the posterior nasal septum  and then the perpendicular plate of the ethmoid bone was fractured and pushed to the opposite side before performing an anterior sphenoidotomy.In the final 59 patients, the mucoperiosteal incision was made at the osseocartilaginous junction of the nasal septum (∼3 cm from the naris). The cartilaginous nasal septum was pushed to the opposite side and the perpendicular plate of the ethmoid bone was excised to expose the anterior wall of the sphenoid sinus, followed by an anterior sphenoidotomy. The rest of the procedure was identical to the previous two methods.The structure of the nasal cavity and sphenoid sinus, position of the apertures of the sphenoid sinus and relevant arteries and the morphological characteristics of the anterior wall of the sphenoid sinus and sellar bulge were observed and recorded. Nasal structures and anatomical anomalies that would affect the surgical approach were photographed and recorded.Comparing the three surgical methods, the approach with the mucoperiosteal incision made at the osseocartilaginous junction of the nasal septum provided a greater surgical view compared with the other two methods. The most common pituitary lesion was pituitary macroadenoma, occurring in 70.9% of patients . There wThe most important landmark in the nasal cavity is the mucosal aperture of the sphenoid sinus, which could be observed under the microscope in 79 patients (53.4%) after pushing the middle turbinate laterally . HoweverIn this region, the first landmark noted was the osseocartilaginous junction of the nasal septum, which could be observed after the septal mucoperiosteum was opened 3 cm from the naris . As illuThe position, thickness, deviation and degree of development of the sphenoid septum varied greatly, which should be identified with the aid of preoperative MRI. In our study, most patients had only one sphenoid septum but multiple sphenoid septa were observed in a few cases . The impThe outcome of TSS is related to the proper removal of lesions and the protection of normal pituitary gland tissue. As shown in In the present study, we delineated important anatomical landmarks for endonasal TSS, including the mucosal aperture of the sphenoid sinus, a blunt longitudinal prominence on the posterior nasal septum, the osseocartilaginous junction of the nasal septum, the ‘bow sign’ of the anterior wall of the sphenoid sinus, the osseous aperture and its relationship with nutrient arteries, the bulge of the sellar floor and the carotid protuberance. These landmarks outline a clear route to the sella turcica providing the optimal view and causing less tissue damage. Based on these landmarks, we successfully accessed the sella turcica and dissected pituitary lesions in all patients without any assistance from intraoperative CT scan and fluoroscopic navigation.et al produced a spheno-sellar point and a spheno-nostril line to guide the head positioning for TSS (et al studied dry skulls and found that the location of apertures varied greatly (et al (et al (et al (et al (Several postmortem and imaging studies attempting to illustrate anatomical landmarks for TSS have been conducted previously . Using c for TSS . However greatly . Tatreauy (et al  reportedl (et al  used CT l (et al . In the l (et al .et al (et al (Over the last 10 years, endoscopic techniques have seen a marked development and led to a trend in transsphenoidal surgical approaches. However, the preference of endoscopic TSS or microscopic TSS depends on the technological refinements and economical restraints. Although an endoscopic approach permits a better view in the sphenoid sinus and the parasellar region , it cannet al  reviewedet al . It shoul (et al ,22, it oAlthough the aforementioned anatomical landmarks are useful to guide the surgical procedure, neuronavigation techniques are invaluable in evaluating the variation of sphenoid sinus and the sellar region, especially in those with residual or recurrent masses in the setting of previous TSS, which may inevitably alter the normal anatomical structure of the skull base . In the Since we mainly focused on endonasal TSS, we did not compare our findings with those using another surgical approach. We believe, however, that the anatomical landmarks for endonasal TSS are also applicable to other approaches.Locating the sphenoid sinus aperture is the gold standard to direct the surgical route of TSS. The ‘bow sign’ and the sellar bulge are critical landmarks for the accurate entry into the sphenoid sinus and sella fossa. These landmarks outline a clear route to the sella turcica with the optimal view causing less tissue damage. The application of these landmarks will aid the reduction of complications and improvement of outcomes of TSS.


Recently, significant advances have been made in understanding the aetiology of adolescent idiopathic scoliosis (AIS) in the area of genetic inheritance. Essential to the success of these studies is the finding of large families with several cases of AIS from which blood samples can be collected and analysed. The emirati culture is unique and encourages large families with many children, often several wives with the same husband, and many cases of consanguinity especially among first cousins. This complex family structure might very well be suited to provide more appropriate examples for the study of genetic heritage in AIS than the more typical western family.The genealogical history of 15 extended emirati families was collected for 4 generations which would approximate that required for the study of AIS. The number of children in each family and the incidence of consanguinity among first cousins were calculated. These data were compared with similar, published data for western families.The average number of children per family among the emirati population was 6.29 (often >10), approximately 3x that of the average western family. In each family there were several examples of multiple wives and first cousin marriages. Two families were found in which at least one person had AIS.These results suggest that the unique, well controlled structure of the emirati families lend themselves to being excellent for extensive study of the genetic inheritance aspects of the aetiology of AIS because of the greater familial component.


Sensory innervation to the scrotum arises from the genital branch of the genitofemoral nerve, travelling with the spermatic cord through the Inguinal canal en route to the scrotum. It lies immediately lateral to the spermatic cord as it emerges from the superficial Inguinal ring and Is involved in the efferent arm of the cremasteric reflex. This causes distortion and apparent shrinkage of the scrotal surface area, and ascent of the Ipsilateral testis. Many surgeons use local infiltration rather than regional anaesthesia. The scrotal anatomy makes it favourable for regional local anaesthetic nerve blocks to be used when repairing or Incising the scrotal skin.The spermatic cord Is identified immediately lateral to the pubic tubercle. The area for injection, including the scrotum, Is sterilised. The spermatic cord is then stabilised and medlallsed using the nondominant hand, and 5ml of 1% lldocaine Is injected subdermally, Immediately lateral to the cord, superficial to the bone.The genitofemoral nerve block provides hemiscrotal anaesthesia, allowing painless manipulation and Intervention In an area that is prone to changes In texture and superficial skin anatomy. This method of regional anaesthesia thereby eliminates problems with handling scrotal skin during the time of anaesthetic infiltration, which may occur on stimulation of the cremasteric reflex. This method also minimises the risk of injury to the male genitalia.


SSIs are one of the most frequent nosocomial infections. To monitor and reduce SSI-rates a good surveillance is crucial. For optimal information, surveillance of incidence of SSIs is preferred above surveillance of prevalence of SSIs. Incidence surveillance however is time consuming.To investigate whether the prevalence of SSIs  can be used to adequately predict the incidence of SSIs (cumulative incidence surveillance).Data were derived from the Dutch surveillance network for nosocomial infections (PREZIES) from 2007 to 2011. The suitability of the Rhame and Sudderth method to estimate incidence of SSIs from prevalence of SSIs was assessed. Also incidence data were used to simulate prevalence data, and prediction models were developed to predict incidence from prevalence and from other relevant variables. Several statistical indices were used to evaluate the performances of the models.Use of the Rhame and Sudderth method to estimate incidence resulted in most estimated incidence rates becoming negative values (below zero). Simulating prevalence from incidence data showed large variation in prevalence depending on the day of measurement. The predictive model best predicting incidence, with a proportion explained variance of 0.31, was the model including the mean length of hospitalization of patients with an SSI (LN), the mean interval between admission and onset of the SSI (INT) and hospital (as random effect). Adding prevalence to the prediction model did not improve the model.It proved not reliable to directly convert prevalence into incidence using the Rhame and Sudderth method. The negative estimated incidence values were the result of the postdischarge surveillance mandatory for the SSI-surveillance in the Dutch surveillance network. Also the simulations and the results of the prediction model indicate that with the current data available it is not possible to accurately predict cumulative incidence of SSIs in Dutch hospitals using point prevalence data.None declared.


The third Thematic Series on flow chemistry published in the Beilstein Journal of Organic Chemistry demonstrates the emerging importance of transforming chemical synthesis in the laboratory from a classical batch approach to continuous processes by using micro- and miniaturized flow reactors. In the past two decades this technology has seen a dramatic increase of visibility. Considering an analyses of the accompanied developments in flow synthesis one has to acknowledge that the topic has shifted among different disciplines with a variety of intensities and focus.In the late eighties and nineties, the idea of miniaturising continuous chemical processes was mainly pursued by chemical engineers. They were fully aware of the quest for an intensification of the process and the advantages associated with continuously operated chemical processes. The benefits of miniaturizing flow systems are evident when considering the excellent heat and mass transfer properties of these small technical devices. Chemical engineers developed beautifully designed reactors, mixers and interfaces for the online monitoring of continuous processes. The major inspiration came from the process and development units in the chemical industry, where continuously operated pilot plants already played a key role. Conceptually, highly modular microreaction systems developed by Ehrfeld Mikrosystem BTS and by CPC (Cellular Process Chemistry Systems) are marvelous examples of these engineered driven achievements.In the late nineties, organic chemists from both industry and academia, which included our group, became involved in the use of microreactors and provided a myriad of synthetic examples. The combined work of experts from engineering and chemical synthesis was highly fruitful and is so until today. This combination of expertise has catalyzed the development of microreactor technology in the applied context of synthesis and production.Chemical engineers depend on input from chemists and synthetic chemists will only advance the field of miniaturized flow synthesis if they are aware of the technical and engineering aspects. This includes the quest for developing analytical devices for online monitoring and feedback loops for optimising synthetic protocols.Several of these aspects can be found in this third Thematic Series on flow chemistry. I am thankful to all my colleagues who contributed with their excellent research to this issue. The Beilstein Team is acknowledged for the handling of the manuscripts and referee reports in a very pleasant and professional manner.Andreas KirschningHannover, August 2013


The onset of double diffusive convection in a viscoelastic fluid-saturated porous layer is studied when the fluid and solid phase are not in local thermal equilibrium. The modified Darcy model is used for the momentum equation and a two-field model is used for energy equation each representing the fluid and solid phases separately. The effect of thermal non-equilibrium on the onset of double diffusive convection is discussed. The critical Rayleigh number and the corresponding wave number for the exchange of stability and over-stability are obtained, and the onset criterion for stationary and oscillatory convection is derived analytically and discussed numerically. The problem of double diffusive convection in porous media has attracted considerable interest during the past few decades because of its wide range of applications, including the disposal of the waste material, high quality crystal production, liquid gas storage and others.Early studies on the phenomena of double diffusive convection in porous media are mainly concerned with problem of convective instability in a horizontal layer heated and salted from below. The double-diffusive convection instabilities in a horizontal porous layer was studied primarily by Nield On the other hand, viscoelastic fluid flow in porous media is of interest for many engineering fields. Unfortunately, the convective instability problem for a binary viscoelastic fluid in the porous media has not been given much attention. Wang and Tan In present research, we perform the linear stability of double diffusive convection in a viscoelastic fluid-saturated porous layer, with the assumption that the fluid and solid phases are not in local thermal equilibrium (LTE). The effects of parameters of the system on the onset of convection are discussed analytically and numerically. The critical Rayleigh number, wave number and frequency for exchange of stability are determined.We consider an infinite horizontal porous layer of depth Assuming slow flows in porous media, the momentum balance equation can be linearized asFor general viscoelastic fluids, the constitutive relations between stress tensor We assume that the diffusion of temperature obeys the following equations, which is a non-equilibrium model between the solid and fluid phases, suggested by The onset of double diffusive convection can be studied under the Boussinesq approximation and an assumption that the fluid The basic state is assumed to be quiescent and we superimpose a small perturbation on it. We eliminate the pressure from the momentum transport equation(4) and define stream function Then the following dimensionless variables are defined asHere the symbol “Hence the boundary conditions areIn this section, we discuss the linear stability of the system. According to the normal mode analysis, the Eqs.(10)–(13) is solved using the time dependent periodic disturbances in a horizontal plane. We assume that the amplitudes are small enough, so the perturbed quantities can be expressed as followsWhere Since The steady onset corresponds to This result is obtained by Banu and Rees Further Eq.(20) can be written asIn the absence of the solute effect, Eq.(21) reduces toThe value of Rayleigh number Case 1: For very small values of When the value of H is very small, the critical value of the Rayleigh number To minimize We also expand Substituting Eq.(26) into the Eq.(25), and rearranging the terms and then equating the coefficients of same powers of H will allow us to obtain the Substituting these values of Case 2: For very large values of For the very large values of Letting Similarly, we expand Substituting Eq.(30) into the Eq.(29), we getThen, substituting these values of For oscillatory onset Effect of different values of conductivity ratio The variation of conductivity ratio on the critical Rayleigh number for stationary mode with the heat transfer coefficient for different values of conductivity ratio is shown in The effect of relaxation time on the neutral curves is shown in From The stationary Rayleigh number increases with an increase in the value of heat transfer coefficient In The effect of Lewis number The onset of double diffusive convection in a binary Maxwell fluid, which is heated and salted from below, is studied analytically using using a thermal non-equilibrium model. Based on the normal mode technique, the linear stability has been studied analytically. The effects of relaxation time, heat transfer coefficient, normalized porosity parameter and other parameters on the stationary and oscillatory convection are discussed and shown graphically. It is found that the increasing relaxation time increases the elasticity of a viscoelastic fluid thus causing instability. The asymptotic solutions for both small and large values of


The ultimate goal of the endodontic treatment is to render the root canal system bacteria-free and to prevent the invasion of bacteria and their byproducts from the root canal system into the periradicular tissues.This special issue presents current research addressing the newest approach to the diagnosis and treatment of the endodontic disease.Fast development of new materials and procedures gave rise for better preparation and filling techniques and enabled higher standards and better quality of root canal treatment. Innovative approach to the anatomy of the roots allows for the predictable preparation of the root canal system. Evaluation of the latest root canal filling materials and restoration techniques helps elucidate factors responsible for the long-term survival of the endodontically treated teeth. The latest molecular biology techniques may help clarify the composition of microbiota in infected root canals and help in the development of new direction in nonsurgical root canal treatment.Igor TsesisIgor TsesisSilvio TaschieriSilvio TaschieriIris Slutzky-GoldbergIris Slutzky-Goldberg


Cetaceans have long been considered capable of limiting diving-induced nitrogen absorption and subsequent decompression sickness through a series of behavioral, anatomical, and physiological adaptations. Recent studies however suggest that in some situations these adaptive mechanisms might be overcome, resulting in lethal and sublethal injuries. Perhaps most relevant to this discussion is the finding of intravascular gas and fat emboli in mass-stranded beaked whales. Although the source of the gas emboli has as yet to been ascertained, preliminary findings suggest nitrogen is the primary component. Since nitrogen gas embolus formation in divers is linked to nitrogen saturation, it seems premature to dismiss similar pathogenic mechanisms in breath-hold diving cetaceans. Due to the various anatomical adaptations in cetacean lungs, the pulmonary system is thought of as an unlikely site of significant nitrogen absorption. The accessory sinus system on the ventral head of odontocete cetaceans contains a sizeable volume of air that is exposed to the changing hydrostatic pressures during a dive, and is intimately associated with vasculature potentially capable of absorbing nitrogen through its walls. The source of the fat emboli has also remained elusive. Most mammalian fat deposits are considered poorly vascularized and therefore unlikely sites of intravascular introduction of lipid, although cetacean blubber may not be as poorly vascularized as previously thought. We present new data on the vasculature of air sinuses and acoustic fat bodies in the head of bottlenose dolphins and compare it to published accounts. We show that the mandibular fat bodies and accessory sinus system are associated with extensive venous plexuses and suggest potential physiological and pathological implications. Since the 1980s, numerous beaked whale mass strandings have been temporally and/or spatially associated with deployment of naval mid-frequency active sonar -type sequelae, suggesting that gas bubble formation may be at the root of some of the observed strandings  by Houser et al. . Specimens used for describing the vascular anatomy were injected with contrast medium into either the venous system or both the venous and arterial systems, following the procedural methodology outlined by Holliday et al. . Prior t® software  on a Gateway desktop with memory and processor upgrades. Following imaging and post-processing, all specimens were thawed and dissected to validate and/or clarify imaged structures. Although the focus of this study was to elucidate the venous morphology in regions of interest in the head of Tursiops, the authors felt that a comparative examination of deep diving odontocete cetaceans would be valuable given the association of deep divers and sonar-related strandings. The authors therefore opportunistically obtained specimens from pygmy and dwarf sperm whales , sperm whales , and Gervais’ beaked whales (Mesoplodon europaeus). Some of the sperm whale and pygmy sperm whale specimens were of sufficient quality and from young enough animals that could fit into the CT gantry. Prior to vascular dissection, those specimens were imaged according to the aforementioned angiographic protocol and the data obtained was used to guide the dissections. As the focus of this study was on Tursiops, only cursory mention is made with respect to findings from the other species.Prior to injecting the vascular contrast material, 5 mL balloon catheters were placed in the vessels to be injected and inflated until a good seal was formed. In specimens that were to be imaged via computed tomography (CT), the vascular system of interest received a mixture of liquid latex and barium sulfate suspension , while vessels only destined for dissection received pure latex . All specimens were refrigerated for 2 days following injections, to allow the latex cast to cure, and if unpreserved with formalin, where subsequently frozen at −20°C. Specimens that were imaged via CT were scanned at the thinnest slice thickness possible based on the specimen length, and whenever possible the volumes were reconstructed to 0.5 mm thickness to allow high resolution imaging of fine caliber vasculature. The resultant DICOM data was post-processed using AmiraWhat is known about the accessory sinus system of the cetacean head varies considerably by species, however delphinid and phocoenid species remain the best described. It is however clear that in all odontocete species there are extensive gas-filled sinuses on the ventral side of the skull. Interestingly, our preliminary research shows that the accessory air sinuses of deep diving odontocetes such as beaked whales, spermwhales, and pygmy and dwarf sperm whales are much larger, relatively, than those of even large delphinid species like pilot whales, and are invested with intricate and seemingly more voluminous venous arrangements. Much of the internal surface of these sinuses is lined with copious masses of convoluted, intercommunicating, and valve-less veins separated from the air spaces by walls so thin that they are translucent Figures  and 5.Tursiops, these lobes are expanded and may meet dorsal to the eye as a supraorbital lobe. The presence of an air-filled sinus on the ventral aspect of the supraorbital process of the frontal bone dorsal to the eye necessitates a fenestration  to bones of the basicranium. The sinus system exists as a bilaterally paired system of blind structures. These sinuses Figure  may exteTursiops has a hamular lobe – within the hollowed hamulus of the pterygoid bone – and an anterior lobe. These two lobes are formed by an indentation of the pterygoid sinus, caused by the lateral laminae of the pterygoid bone and palatine bones. This bony structure is lacking in the pygmy sperm whale (Kogia breviceps) and thus, distinction of those lobes is meaningless. At its caudal end, the Pty sinus connects to three smaller sinuses, all of which are relatively close to the region occupied by the ear, the TMJ, and the attachment of the hyoid apparatus via the tympanohyal cartilage: the most lateral of these three sinuses (the middle sinus) is associated with the TMJ; a slightly more caudomedial sinus (posterior sinus) is associated with the tympanohyal joint and is bordered by the paroccipital crest; and a caudomedial sinus (peribullar sinus) that helps separate the tympanic bulla from the adjacent bones.The Pty sinus in Tursiops, have a deep indentation in the Pty sinus. In contrast, deep divers such as Kogia lack or have less distinct anterior and hamular lobes.Despite the variable geometry of the recesses and fossae of the sinus system, the bony associations of the sinuses follow some similar patterns among all odontocetes studied thus far. Delphinid species show marked similarity among the different species, while kogiids, physeteriids, and ziphiids all show similarity between themselves. In delphinids, the lateral wall of the pterygoid sinus is partly encased by the bony lateral laminae of the pterygoid and palatine bones. Conversely, in deep diving species like ziphiids, kogiids, and physeteriids, the lateral wall of the Pty sinus is composed entirely of soft tissue capable of collapsing onto itself. When manually manipulated, the Pty sinus is easily closed under the weight of the surrounding tissues, suggesting that maintaining it in an expanded state may require a degree of pressurization. Although the significance of these features is unknown, it is difficult to ignore the common threads among the non-delphinid deep diving cetaceans. Shallow divers such as Tursiops extend much farther into the orbit than those of Kogia; these lobes join distally to form the supraorbital lobe of the Pty sinus, on the ventral aspect of the supraorbital crest of the frontal bone.The sinuses of the accessory sinus system follow the contours of slight depressions , and extra-mandibular fat body (EMFB) Figures  and 6–8 The melon fat is primarily drained by a multitude of veins that converge with the veins draining the rest of the tissues of the region , the external jugular vein of the bottlenose dolphin is the main drainage route of the pterygoid vasculature although the internal jugular vein can be the primary drainage The lateral branch of the facial vein The middle branch of the facial vein The third and most medial branch of the facial vein The first and most proximal  contribution is formed by numerous anastomoses The second and third branches arise in common from a bifurcation of the distal internal jugular vein. The proximal of the two branches curves sharply rostrad to become the ventral petrosal sinus The third branch extends vertically from the bifurcation of the internal jugular vein, to enter the jugular foramen as the terminus of the internal jugular vein On its course to the rostroventral aspect of the brain case, the maxillary vein sends dorsorostrad oriented veins of a plexiform nature Before it breaks up into the countless veins that compose the pterygoid plexus  and by Walmsley , ventral to the ventral petrosal sinus. This is an unusual location for the cavernous sinus.The paired cavernous sinuses of domestic mammals form a ring-like venous structure around the pituitary gland . The two lateral components are connected across the midline via structures much like the intercarvernous sinuses of domestic mammals. This venous loop is therefore consistent in location and drainage with the cavernous sinus of terrestrial mammals, and seems contradictory to the statements of Fraser and Purves  could be erected by way of the internal carotid…” This appears to conflict with our findings as well as Boenninghaus’ illustration that the corpuscavernosum is venous in nature, connected by ventral tributaries to the pterygoid and maxillary veins , anterior lobe venous plexus (purple), and IMFB plexus (yellow).Click here for additional data file.


The ribosome is a large ribonucleoprotein complex that carries out protein synthesis in all kingdoms of life by translating genetic information encoded in mRNA into the amino acid sequence of a protein. The nascent polypeptides escape the peptidyl transferase center through the ribosomal exit tunnel that spans the entire large subunit. The tunnel is involved in the control of co-translational protein folding processes, the regulation of elongation and the inhibition of the protein synthesis by antibiotics . Since tWe thus set out to analyze global and local flexibility characteristics of the ribosomal exit tunnel by constraint counting on topological network representations of large ribosomal subunits from four different organisms ,3. The a


Neurotransmitter transporters of the SLC1 and SCL6 family are found on presynaptic neurons and on glia cells. The function of these transporters is the termination of neurotransmission by the rapid removal of the neurotransmitter molecules from the synaptic cleft. These transporters couple substrate transport to ion gradients of sodium and chloride. Almost all of the eucaryotic transporters have been described to function as oligomers. However, the forces stabilizing the oligomeric state are not well understood. No crystal structures of eukaryotic transporters are available, but recently crystal structures of bacterial homologs thereof have been solved: GltPh (SLC 1 family) was found as a trimer, LeuT (SLC6 family) was crystallized as a dimer. These homologous crystal structures allow rationalizing on the driving forces that stabilize the eukaryotic counterparts.The crystal structures of LeuT and GltPh were obtained from the Protein Data Bank (PDB). We identified the interfaces between the protomers and analyzed hydrogen bonding, hydrophobic and hydrophilic interactions as well as size and width of the interface area.We investigated the protein-protein interfaces between the transporter protomers and identified the dominant forces that stabilize the oligomer. These consist of hydrophobic interactions between the aliphatic side chains within the interface and of polar interactions by hydrogen bonds between hydroxyl groups.The contributions of different forces to the stability of oligomer assemblies vary between proteins. While the hydrophobic mismatch is a prominent contributor to the stability of the GltPh transporter, it plays a minor role for LeuT, where helix packing and aromatic interactions seem to dominate.


Eucalyptus trees (family Myrtaceae) are well-known for their high foliar content of several classes of secondary metabolites and these have a strong effect on the feeding patterns of several species of marsupials and at least some insects. Best known are the essential oils, which is mostly a mixture of terpenoids, but there are also significant concentrations of flavonoid and formylated phloroglucinol compounds. There is extensive quantitative and qualitative variation within and between species of Myrtaceae in these chemical groups and all appear to be under strong genetic control with heritabilities (2H) between 0.3 and 0.9. As well as being important ecologically, the terpenes in particular are valued as industrial and medicinal products and Australia supports a strong essential oil industry focused on Eucalyptus and Melaleuca foliar oils.Eucalyptus grandis genome provides the opportunity to discover the genetic makeup of the biosynthetic pathways for secondary metabolites. We present data from pathways leading into the biosynthesis of terpenes, flavonoids and lignins. The homology of genes and gene families were investigated and compared to a variety of other species including poplar (Populus trichocarpa), grape (Vitis vinifera) and apple . For example, terpene synthases  has 120 members in the genome of Eucalyptus grandis, compared to 44 and 99 in poplar and grape, respectively  studies that investigated variability in secondary metabolites and wood properties in eucalypts. This approach allowed the discovery of candidate genes for a large number of QTL.The Eucalyptus globulus, investigating 200 SNPs and roughly 40 traits ranging from terpenoids to terpene-adducts to flavonoids and to tannin-related traits. We discovered several significant trait associations between allelic variants in the chloroplastic MEP pathway and monoterpenes and between the cytosolic MVA pathway and sesquiterpenes, as well as one allelic variant in a prenyl pyrophosphate synthase that associates with the ratio of monoterpenes to sesquiterpenes. Loci with significant associations were mapped to the Eucalyptus grandis genome and compared to published QTL datasets that investigated similar traits. These results represent the first species wide analysis of the molecular basis of quantitative variation in secondary metabolites in any tree.Understanding the genetic basis of variations in quantitative traits provides insights into ecosystem function and at the same time may help breeders in the essential oil industry. We have characterized trait associations with polymorphisms from The publicly available genome sequence of Eucalyptus grandis is a great resource that can be applied to a variety of questions including the genetic make-up of gene families for biosynthesis of plant secondary metabolites, genome organization of these genes and evolution of traits such as resistance to herbivores or the ability to re-sprout after fire. Combining studies of association genetics, QTL studies together with the genome sequence helps to shed light on the underlying control mechanisms of phenotypic variation.


Prophylactic treatments of migraine are an important part of the management of the disease. Only one survey concerning this topic was performed in 2000 in France among GPs. This survey was however performed before the French migraine guidelines with a large use of dihydroergotamine at this time.To evaluate the practices of GPS in the North of France concerning the prophylactic treatments of migraine management and to compare them with the French Guidelines.A self-administered questionnaire concerning prophylactic treatments of migraine was mailed in 2011 to 307 GPs in two big cities in the North of France (Lille and Roubaix). We analysed the data and compared them with the French Guidelines.142 GPs answered to the questionnaire (46.2 %). 85% of GPs use prophylactic treatments of migraine when the patient has 4 to 5 migraine attacks per month. The first line treatment are beta-bloquers (BB) (60%). The first objective is to reduce the migraine attacks frequency by 50% at 3 months for 53% of the GPs and the second to increase the quality of life in 45%. 59% of GPs prescribe prophylactic treatment of migraine for a 6-12 months duration.GPS in the North of France take into account the bad quality of life of migrainers to start a prophylactic treatment. They use in majority the recommended prophylactic treatments of migraine and during a correct duration according the French Guidelines.There is a dramatic increase since 2000 of the use of BB in France as first line prophylactic treatment of migraine. French guidelines of migraine seems to be useful for GPs.


Protein-ligand complexes are often consulted for the understanding of binding modes and mechanisms of action as well as the development of novel drugs. Unfortunately the resolution of most x-ray structures is too low to resolve hydrogen atoms. However, hydrogen positions play a major role in the analysis of important interaction types as hydrogen bonding or metal interactions. Therefore, it is important to predict the orientation of hydrogen containing rotatable groups as well as sensible protonation and tautomeric states of both protein and ligand. While in most cases these degrees of freedom are still manageable for the protein and therefore incorporated in the models of the most common prediction tools for hydrogen placement -3, the cWe present a new method for the prediction of hydrogen positions in protein-ligand complexes that considers tautomeric variability of the ligand in addition to common degrees of freedom. Beginning with a random tautomeric state, different reasonable tautomers of the ligand are enumerated and their relative stability is estimated on the basis of a heuristic scoring scheme. This tautomerism model is integrated in the hydrogen placement application Protoss .Our approach permits an enhanced automatic prediction of hydrogen positions, especially for ligands that exhibit tautomers with similar stability but different interaction facilities. Furthermore we were able to reproduce the ligand tautomers that were proposed in several studies of tautomerism preferences in protein-ligand complexes.


The fossil record of Caviidae is only abundant and diverse since the late Miocene. Caviids belongs to Cavioidea s.s. The first two phases involve two successive radiations of extinct lineages that occurred during the late Oligocene and the early Miocene. The third phase consists of the diversification of Caviidae. The initial split of caviids is dated as middle Miocene by the fossil record. This date falls within the 95% higher probability distribution estimated by the relaxed Bayesian molecular clock, although the mean age estimate ages are 3.5 to 7 Myr older. The initial split of caviids is followed by an obscure period of poor fossil record (refered here as the Mayoan gap) and then by the appearance of highly differentiated modern lineages of caviids, which evidentially occurred at the late Miocene as indicated by both the fossil record and molecular clock estimates.A phylogenetic analysis combining morphological and molecular data is presented here, evaluating the time of diversification of selected nodes based on the calibration of phylogenetic trees with fossil taxa and the use of relaxed molecular clocks. This analysis reveals three major phases of diversification in the evolutionary history of Cavioidea The integrated approach used here allowed us identifying the agreements and discrepancies of the fossil record and molecular clock estimates on the timing of the major events in cavioid evolution, revealing evolutionary patterns that would not have been possible to gather using only molecular or paleontological data alone. Estimating the timing of evolutionary diversification events is the field of major interaction between paleontology and molecular biology. During the last two decades the alternative evolutionary timescales for different taxonomic groups were the focus of intense debates between paleontologists and molecular biologists Rodents provide an interesting case for analyzing the interaction between fossils and molecules, as this is a diverse group with a relatively complete fossil record. Rodents are the most diverse group of mammals at present, which include more than 2256 species representing 41% of all mammals Within caviomorphs, Cavioidea is crucial for understanding the diversification of South American rodents given that it includes the greatest morphological disparity  clustering the extant Caviidae and Hydrochoeridae together with a diverse assemblage of primitive taxa of the extinct family Eocardiidae, given the presence of unique dental and mandibular modifications . Recent phylogenetic analyses of this group based on morphological characters s.s. but retrieved a paraphyletic arrangement of “eocardiids” as successive sister taxa of the crown-group comprised of cavies, maras, and capybaras.Different authors, however, have variously interpreted the taxonomic content of Cavioidea. The most inclusive and traditional conception of the group includes four families: Dasyproctidae (agouties), Cuniculidae (pacas), Caviidae (cavies and maras), and Hydrochoeridae (capybaras) s.s. has provided a wealth of new data to understand more thoroughly the relationships of the group, such as the close affinities of the capybara (Hydrochoerus) and cavies  that have been corroborated in broad-scale phylogenetic analyses of hystricognath rodents Hydrochoerus within the multiple representatives of cavies and maras used in that study, being the sister group of the Rock cavy, Kerodon. This result was incongruent with traditional morphological classification schemes, but has been subsequently corroborated by phylogenetic studies based on morphological characters Regarding the relationships of the extant lineages, the availability of DNA sequences of extant species of Cavioidea sensu stricto represents the clade formed by Caviidae and its stem group , and Cavioidea as an even more inclusive group that also includes Cuniculidae and Dasyproctidae, the two other lineages leading to the extant pacas and agouties.Therefore the clade Caviidae can be applied to the cluster of the crown-group of three major living lineages: cavies (Caviinae), maras (Dolichotinae), and capybaras (Hydrochoerinae). These three major lineages of extant caviids are well differentiated from a morphological and ecological perspective. Cavies are usually small-bodied taxa that inhabit a variety of environments  and they feed on diverse types of plants. Maras, instead, are much larger, adapted to cursorial habits with elongated hind limbs, and exclusively inhabit arid areas with coarse grass or scattered shrubs. Capybaras are not only the largest rodents alive but are also characterized by their highly apomorphic dentition  and inhabits densely vegetated areas around freshwater bodies s.s. and its crown-group Caviidae, using the information of the fossil record and molecular clock estimates . The fossil record of Cavioidea s.s. includes a large diversity of extinct species recorded in South America since the late Oligocene (24.5–29 Ma). The fossil evidence indicates that Cavioidea s.s. diversified after the arrival of rodents in South America s.s.–previous hypotheses on the group, including the traditional interpretation of gradual evolution, need to be revisited within an explicit phylogenetic context.The major focus of this contribution is the analysis of the timing and diversification patterns in the evolutionary history of Cavioidea s.s. provide an interesting test-case to evaluate the congruence between divergence estimates based on the fossil record and the molecular clock.Furthermore, the availability of molecular data for species of Caviidae also allowed exploring the divergence time of this clade using different approaches to the molecular clock s.s. Finally, we compare the timing of these events as inferred from the fossil record evidence and through the use of relaxed molecular clocks s.s.Here we present new phylogenetic results based on a morphological dataset that expands previously published evidence Eocardia spp., Schistomys, Matiamys) and in the alternative positions of the fragmentary crown caviid taxon Allocavia (see Document S1.doc). The reduced strict consensus tree of the MPTs pruning Allocavia resolves the interrelationships of the three major lineages of Caviidae: Caviinae, Dolichotinae, and Hydrochoerinae  of the parsimony analysis of the combined dataset  differ in the interrelationship of some fossil forms of stem cavioids . All these forms appear later in the fossil record, in early Miocene beds referred to the Colhuehuapian SALMA . This implies a previously undetected radiation of all basal lineages of Cavioidea s.s. that must have occurred at least by the late Oligocene. The optimization of character transformations in these basal nodes of Cavioidea s.s. indicates that major evolutionary novelties must have appeared in this late Oligocene radiation, including changes from a mesodont to a protohypsodont dentition and other dental modifications such as the appearance of cement and enamel discontinuities and the loss of fossettes/ids during ontogeny.The discovery of a basal cavioid radiation in the late Oligocene contrasts with previous interpretations about the early evolution of Cavioidea s.s., so it is possible that the actual diversification of this group predated the Deseadan SALMA (24.5–29 Ma). The pre-Deseadan record of fossil rodents in South America however provides relevant information to evaluate this possibility. The youngest pre-Deseadan rodent assemblage is known from La Cantera horizon of Central Patagonia . The La Cantera rodents include plesiomorphic taxa of Cavioidea (Dasyproctidae?) and representatives of Octodontoidea and Chinchilloidea s.s. in all these pre-Deseadan rodent faunas is compatible with the hypothesis of a basal radiation of this group close to or in the late Oligocene.The ghost lineages provide a minimum estimate for the age of these basal nodes of Cavioidea s.s. The most ancient records of euhipsodont cavioids come from the early Miocene Santa Cruz Formation of Central Patagonia  and the five oldest euhypsodont species of Cavioidea s.s. . The sudden appearance of multiple euhypsodont lineages at this time suggests the occurrence of an evolutionary radiation that not only includes the five above mentioned taxa but also three ghost lineages leading to slightly younger taxa of the Colloncuran SALMA  E. robertoi, and 3) the clade formed by E. robusta and more derived cavioids  within this clade results in markedly suboptimal topologies .The euhypsodont condition represents the presence of teeth with continuous growth (lacking a root) and was one of the major evolutionary novelties in the history of Cavioidea oids see . Thus, uoids see  have booThe exceptional Santacrucian fossil record and the sudden appearance of a high diversity of euhypsodont cavioids can be interpreted in two alternative ways. On the one hand, the fossil record could be actually capturing the early offshoots of a major radiation, characterized by the acquisition of a key evolutionary innovation (euhypsodonty), which has been interpreted as an adaptation to grazing. The acquisition of the euhypsodont condition may have been a critical innovation at this time given the major environmental changes recorded in Patagonia, which includes high volcanic activity related to the uplift of the Andes  and b) that the three modern and morphologically distinct lineages of Caviidae  were already present, abundant, and diverse about 6.1–9.07 Ma  the initial split of Caviidae in three major lineages must have occurred at least 11.8–13.5 Ma . These estimates, however, were based on different DNA sequences and molecular clock methods so that it is difficult to compare their reliability and determine the causes of their differences.Previous molecular clock estimates on the time of diversification of Caviidae resulted in disparate dates Given the multiple nodes that are paleontologically dated by the phylogenetic study presented here , we testThe results of the analyses involving different number of calibration constraints and their prior probability distributions are summarized below for the time of diversification of Caviidae and the diversification of the major modern lineages of Caviidae see also  and 3.P. pridiana; Laventan age; purple column in Owing to the incorporation of fossils in the phylogeny, these are the most tightly constrained analyses of the diversification timing of Caviidae . The estGalea. The age of one of these nodes was constrained by a prior distributions  but the ages retrieved for the diversification of Dolichotinae  lies outside the 95% HPD  when this node is not calibrated is remarkably old, with mean ages of 14.78 and 17.45 Ma and 95% HPD  the mean ages of these nodes fall within the Chasicoan SALMA see . However 95% HPD  lying ouThese analyses retrieved disparate results on the time of diversification of Caviidae , the mean ages of the Dolichotinae and These results indicate a considerable degree of rate heterogeneity among groups of Cavioidea. The two oldest and most basal calibration constraints  lead to inferences of a much slower rate of evolution than when the caviine calibration constraint (node 4) is used, and rate estimates derived from calibrations of node 3 are intermediate between these two extremes. Consequently, estimates on the age of Caviidae and on the radiation of the major modern lineages of caviids based only on the basal calibrations  are much older than those retrieved when node 4 (or node 4 and node 3) is used for calibrating the relaxed molecular clock . This sesensu stricto and the crown-group Caviidae. The cumulative number of lineages (counting those leading to both extinct and living taxa) plotted across time reveals the diversification events of this group inferred from fossils and the molecular clock  and is recognized mainly by the four ghost lineages of forms that appear later in the fossil record . Only two species are known up to date from this age, which provide the minimum estimate for the age of basal nodes of Cavioidea s.s. Although a more gradual diversification of this group might have occurred before the Deseadan SALMA, the older rodent assemblages at Tinguiririca and La Cantera lack members of this clade. An initial radiation during the late Oligocene fits the available fossil data and the morphological phylogeny.As noted above, the Deseadan radiation 1 in  involvesThe Santacrucian radiation 2 in  is the eThe diversification of the crown-group Caviidae , as shown by the diversification plot . Alternatively, the Colloncuran Guiomys unica can be placed within Caviidae with a single extra step (pushing back the time of diversification of Caviidae to the Colloncuran and decreasing the discrepancy with the molecular clock estimates).The uncertainty on the relaxed molecular clock estimates is however relatively large, and the 95% HPD  and new remains of incompletely known taxa , as well as new sequences to base molecular clock estimates on a more extensive dataset are all necessary steps to solve this apparent discrepancy .The molecular clock estimates, therefore, indicate there is a high probability that the fossil record is currently missing the first few million years of caviid evolution, although the breadth of the 95% HPD and the possible alternative positions in slightly suboptimal trees of some key fossils indicates the two sources of information are not yielding entirely incompatible estimates. Further studies on some of these fossils  or as a crown caviid that bears plesiomorphic dental characters  that resemble the condition of basal hydrochoerines  but is markedly different from the highly modified condition of more derived hydrochoerines from the late Miocene . The scarce available evidence suggests that the initial diversification of Caviidae  can be of substantial duration, and many times they do overlap with the first appearance datum of fossil taxa, as in the case of the initial diversification of Caviidae and the Laventan age. In many instances, therefore, the discrepancies between the molecular clock and the fossil record disappear when then 95% HPD are considered.Microcavia+Cavia). A striking difference exists between the age inferred by the molecular clock when this node is not calibrated and the first appearance of members of this clade in the fossil record. As noted above, the molecular clock estimates are likely too old and suggest the fossil record of caviine rodents would be missing 60% of its evolution. We suggest it is more likely this caviine lineage has a higher evolutionary rate in comparison with other cavioid rodents (at least for these genes). Caviines have a reduced body size (and related life-history traits such as shorter generation times) in comparison with other cavioid rodents , providing another case of correlation between high evolutionary rates and small body size if this hypothesis is correct. More data are needed to test this correlation, as well as to provide reliable molecular clock estimates for Caviinae. New data must include both a more extensive taxon sampling among caviines for these sequences and further studies on fossil caviines to provide alternative calibration points within this clade.One of the interesting outcomes of the 30 different molecular clock analyses conducted here is the identification of the sensitivity of the results to the inclusion or exclusion of node 4  comes from northern South America .Estimating the divergence time of clades based on phylogenetic studies is the area of most intense interaction (and conflict) between paleontology (providing fossils with dates) and molecular systematics (providing molecular clock estimates), as both areas provide information for understanding the tempo and mode of the evolution of a group. Recent efforts and progress have been made to incorporate different kinds of uncertainties to both molecular clock methods s.s. These analyses result in a global picture on the evolutionary history of Cavioidea s.s., including the origins and diversification of Caviidae, one of the most remarkably disparate lineages of living rodents. Three major evolutionary phases are recognized in the history of the group. The first two were radiations of basal forms that acquired the dental hallmarks of the groups: the appearance of protohypsodont forms in the Deseadan radiation of Cavioidea s.s. and of euhypsodont cavioids in the Santacrucian radiation, the evidence coming mostly from the Patagonian fossil record. The third phase was the diversification of Caviidae, which seems to have occurred in two temporally discrete episodes, the initial split of the group in three major lineages and the subsequent diversification of its modern clades, which are highly differentiated morphologically and ecologically.Our study integrates morphological and molecular data gathered from extinct and extant taxa into a phylogenetic analysis of Cavioidea A general agreement exists on the divergence dates estimated from molecular data and the fossil record. Molecular clock estimates places the origin of most modern lineages of caviids close to the Chasicoan, which coincides with the earliest appearance in the fossil record of the modern caviid lineages, which are characterized by remarkably distinct body plans, body size ranges, and ecological roles .However, the timing of the initial diversification of Caviidae was detected as the major discrepancy. The initial split of Caviidae is inferred to occur at Laventan times by paleontological evidence or perhaps as much as 7 million years earlier using a relaxed molecular clock. However, the uncertainties of the paleontological and molecular estimates reveal that more data is needed to solve this apparent conflict between the fossil record and the molecular clock.From a paleontological point of view, a more extensive knowledge of pre-Laventan faunas are critical to clarify the time and place of the initial diversification of Caviidae. Although the record of pre-Laventan faunas  is geographically extensive, rodent faunas from these ages are all restricted to the southern half of South America , limiting our ability to localize the group's origin.s.s.Finally, increasing the amount of molecular data (taxon and gene sampling) is also needed to achieve a more robust phylogenetic framework for caviid evolution and to generate more robust molecular clock inferences. The prospective integration of new sources of evidence into an integrated approach will be unavoidable steps for understanding the evolutionary history of Cavioidea s.s. that were selected as the ingroup. The dataset include all the known stem-group fossil taxa (“eocardiids”), at least one representative of each extant genus of Caviidae, and nine extinct species of caviids (see Document S2). Outgroup taxa included representative species of Dasyproctidae, Cuniculidae, and Echimyidae, the latter of which was used to root the topologies (see Document S2). The character sampling is based on 69 craneo-mandibular and 27 dental characters (see Document S3).The morphological dataset was expanded from a recent study Ghr), intron 1 of transthyretin (Tth), 12 subunit ribosomal RNA (12s), and cytochrome b (cyb). Sequences of these genes were available for nine extant representatives of Caviidae and the three outgroup taxa (see Document S2 for GenBank accession numbers). Sequences of two of the outgroup taxa (Proechimys and Dasyprocta) have been assembled from two different species of each genus (see Document S2). These sequences have been successfully used by previous authors to resolve relationships of caviomorph and/or cavioid rodents The DNA sequences of extant caviid species were gathered from GenBank for two nuclear and two mitochondrial genes: exon 10 of growth hormone receptor (http://datadryad.org/ (doi:10.5061/dryad.v5p71).The phylogenetic dataset consisting of the 96 morphological characters and the 4014 characters of the four genes  is available as Dataset S1 and also at DataDryad 12s, cyb, Ghr, and Tth) were compiled from several previous analyses (see Document S2), and were aligned using CLUSTAL X 12s gene, 1140 bp for cyb gene, 1099 bp for Tth gene, and 814 bp for Ghr gene.The DNA sequences of each of the four genes , scoring fossil taxa with missing entries for the DNA partitions. This dataset contained a total of 40 taxa and a total of 4110 characters. An equally weighted parsimony analysis was conducted treating gaps as missing data in TNT 1.1 The combined dataset of the 96 morphological characters was concatenated with the DNA sequences of the four genes  were input as separate partitions for the Bayesian analyses, model selection was performed using AIC (Akaike Information Criterion) cyb that used GTR+I+Γ), a linked clock model , and tree priors assuming a Yule process. Four independent MCMC runs of 10,000,000 generations (sampling every 1000 generations) were run independently for each of the 30 analyses we conducted using different calibration constraints (see below). Results of the four independent MCMC runs were integrated and summarized for checking convergence using the BEAST v. 1.6 package Bayesian analyses were conducted on the molecular data in BEAST v. 1.6 Bayesian approaches to molecular clock estimates, as implemented in BEAST v. 1.6, allows using different prior probability distributions to calibrate selected node ages . As noted by several authors in recent years Prior distributions of the ages of these four nodes were defined based on the available chronostratigraphic information of the fossil record, considering the phylogenetic placement of fossils in the phylogenetic analysis see  and the Normal distributions were centered on midpoint age of the period of time to which the fossil-bearing formation has been referred. The standard deviation was set so that the 95% probability distribution reached the upper and lower bound of the age of the lithostratigrapic unit , and including in the 95% prior probability distribution the age of the most recent sediments in which representatives of the node being calibrated are absent, but numerous remains of its stem-group or other caviid lineages are known . This distribution largely ignores the second source of uncertainty  and places a strong belief in that the dasyproctid from Tinguiririca is actually very close (in time) to the divergence time of Cavioidea. The second approach uses a gamma distribution, with a hard minimum bound at 31.5 Ma and its long tail extends the 95% probability density back to 45 Ma, representing the upper bound of the available dates of oldest record of caviomorphs from South America Andemys termasiAndemys termasi to calibrate Cavioidea.Finally, given the scarcity of the available material to constrain the age of this node and the lack of an explicit phylogenetic analysis including s.s. plus the lineage of the family Cuniculidae. The fossil record of Cuniculidae is extremely poor and only starts in the Pleistocene s.s., in contrast, has an extremely rich fossil record s.s. are Asteromys punctus and Chubutomys simpsoni, both known from few specimens found in the late Oligocene beds of Patagonia (Deseadan SALMA) of the Sarmiento Formation s.s. is strongly supported in by the morphological data of the phylogenetic analysis presented here  and bootstrap and jackknife frequencies above 96% , ignoring the second source of uncertainty. The second approach uses a gamma distribution, which puts a hard minimum bound at 24.5 Ma and its long tail extends the 95% probability density back in time to the age of the youngest rodent assemblage that lacks forms of Cavioidea Kerodon). The fossil record of Kerodon is only known from scarce material of the late Pleistocene of Brazil Hydrochoerus ; this ignores the phylogenetic uncertainty of the fragmentary remains with possible hydrochoerine affinities in older sediments . The second used a gamma distribution, with a hard minimum bound at 6.1 Ma and a long tail to extend the 95% probability density back to the age of the Laventan SALMA, which is the youngest rodent assemblage that is well sampled and lacking forms that could potentially belong to Node 3 . As in previous cases, we have explored both approaches but consider the second option better represents the uncertainties in the fossil record of early hydrochoerines.Microcavia or Cavia than to Galea. The earliest fossil members of Cavia come from the San Andrés Formation . Forcing M. chapalmalensis to be positioned outside the Node 4 requires a minimum of five extra steps demonstrating the strong support for its inclusion within this node. The minimum age of the Chapadmalal Formation has been dated at 3.27 Ma using K-Ar radioisotopes MicrocaviaMicrocavia  or have an even more basal position, but more complete remains are needed to place them confidently.analysis  and comeDolicavia minuscula was recovered in a basal polytomy within the lineage leading to the genus Microcavia together with Paleocavia impar .Allocavia) as well as numerous forms of Dolichotinae and Hydrochoerinae Microcavia and Cavia (Node 4).The rodent fossil record of the older sediments of the Chasicó Formation  provides confident information to place a maximal bound for the origin of this node. The Chasicoan fossil record contains remains of caviine-like caviids . The second approach used a gamma distribution, with a hard minimum bound at 4 Ma and a long tail that extended the 95% probability density back to the Chasicoan, which is the youngest well-known rodent assemblage lacking taxa that belong to Node 4 . As in previous cases, we have explored both approaches but believe the second option better represents the uncertainties in the fossil record of early caviines.As with other nodes, we explored two different prior probability distributions for the age of Node 4 based on the position of fossil taxa in the most parsimonious trees of our analysis. The first used a normal distribution whose 95% probability density encompasses the range of radioisotopic ages that bracket the fossiliferous levels of the Monte Hermoso Formation (4–5.3 Ma); this ignores the uncertainty associated with the possible presence of Paleocavia; Montehermosan SALMA) is only poorly supported within Node 4, we have also tested alternative calibrations for this node. We have conducted exploratory runs of the Bayesian analysis calibrating this node with the age of Microcavia chapalmalensis , which is the only fossil of this clade that is robustly supported by the morphological data of the phylogenetic analysis (see above). The results of this analysis are largely similar in terms of the molecular clock estimates for Caviidae (mean age  = 17.5 Ma) and place the diversification of dolichotines and Galea within the Chasicoan SALMA. Therefore, the estimates of interest for our purposes do not seem to be sensitive to the alternative ages that can potentially be used for calibrating Node 4.Finally, given the oldest member of this clade Click here for additional data file.Document S2List of taxa used for the Phylogenetic Analysis and GenBank accession numbers.(DOC)Click here for additional data file.Document S3List of morphological characters used in the phylogenetic analysis.(DOC)Click here for additional data file.Dataset S1Combined data matrix containing molecular and morphological characters in Nexus format.(TNT)Click here for additional data file.Script S1Script for calibrating phylogenetic trees using the chronostratigraphic information for fossil taxa in TNT .(TXT)Click here for additional data file.


We investigate the influence of network structure on the dynamics of neuronal networks, with a focus on the emergence of synchronous oscillations. Network structure is specified using the framework of second order networks, a network model that captures second order statistics (correlations) among the connections between neurons. We demonstrate that the frequency of a chain motif in the network plays a crucial role in influencing network dynamics, not only modulating the emergence of synchrony but also possibly increasing the range of possible network behaviors.


The authors wish to retract the PLOS ONE article ”Antibiotics threaten wildlife: circulating quinolone residues and disease in avian scavengers”.The Ethics Committee of the Spanish Superior Council of Scientific Research (CSIC) has carried out a formal investigation in relation to concerns about potential scientific misconduct by Jesús A. Lemus, one of the authors of this article. The investigation has questioned the validity of the laboratory analyses conducted by Dr. Lemus; concerns were also raised about the existence of co-author Javier Grande.Given the ephemeral nature of the material used , we are unable to repeat these analyses with the same samples in order to verify the presence of veterinary drugs and pathogens. We sincerely apologize for any inconvenience to the readership of PLOS ONE.


One of the major differences of the DG compared to other brain regions is the finding that the dentate gyrus generates new principal neurons that are continuously integrated into a fully functional neural circuit throughout life. Another distinguishing characteristic of the dentate network is that the majority of principal neurons are held under strong inhibition and rarely fire action potentials. These two findings raise the question why a predominantly silent network would need to continually incorporate more functional units. The sparse nature of the neural code in the DG is thought to be fundamental to dentate network function, yet the relationship between neurogenesis and low activity levels in the network remains largely unknown. Clues to the functional role of new neurons come from inquiries at the cellular as well as the behavioral level. Few studies have bridged the gap between these levels of inquiry by considering the role of young neurons within the complex dentate network during distinct stages of memory processing. We will review and discuss from a network perspective, the functional role of immature neurons and how their unique cellular properties can modulate the dentate network in memory guided behaviors.The dentate gyru The dentate gyrus (DG) hippocampal region is one of the most plastic regions in the mammalian brain, exemplified by its ability to generate adult-born principal neurons that integrate into the pre-existing network. Great effort has been made to understand the process and regulation of neurogenesis, and recently several groups have sought to determine the functional role of adult-born neurons in the DG. We postulate that in order to fully understand the functional role of adult-born neurons in the DG it will be necessary to consider the complexity of the local neural-network into which they integrate, focusing on network level mechanisms of DG computations and studying the contribution of adult-born neurons to those computations.We will focus on one aspect of the DG that is critical to several theories of the role of the DG in memory processing: the observation that activity levels in the DG network are sparse. Both the proportion of active neurons and the action potential rates of active neurons are relatively low compared with other brain regions. Intuitively the observation of low activity levels introduces a puzzle; why would such a silent network require the constant addition of adult-born neurons? In other words, what is the relationship between adult-born neurons in the DG and the sparse encoding scheme implemented by the network? We will discuss two possibilities in the context of recent findings in the field, one, that adult-born neurons are themselves the small proportion of active cells in the DG at any given time and are thus “carrying the message,” or two, that adult-born neurons impose low activity levels in the DG by recruiting local inhibitory networks which act to suppress activity in mature DG granule cells, allowing a few to fire at any given time, thus “dictating the tone.” To gain insight into these possibilities we will review the unique properties of adult-born neurons in the context of the complexity of the greater DG network, focusing on linking proposed behavioral roles for adult-born neurons with long-standing theories of DG network coding. Throughout, we will highlight future experiments that could be done to properly bridge the gap between function and mechanism.Classically, the DG is thought of as the first processing station of the hippocampal formation, comprising the first synapse of the “tri-synaptic pathway.” In simplified circuit diagrams, signals propagate from associative cortices, the lateral and medial entorhinal cortices, to the granule cells of the DG. From there signals are sent to downstream area CA3 and from CA3 to CA1. In reality, signals do not necessarily propagate in one direction along the tri-synaptic pathway, but instead ping-pong within sub-regions through associative pathways  in CA3, however, they still appear structurally immature because they have fewer synaptic vesicles and active zones, and contact fewer CA3 spines compared to mature DGCs (Faulkner et al., The DG recruitment of GABAergic interneurons in the CA3 field may be a crucial component to proper memory encoding. A recent study has demonstrated that, during learning, structural changes of synapses from DGCs to CA3 interneurons determines memory precision (Ruediger et al., An important role for immature DGCs as the active population of the DG network is also suggested by one recent study that has silenced the activity of all DGCs except immature DGCs and shown that dentate dependent memory is facilitated. Nakashiba et al. , using gThe most critical component that determines the sparseness of the DG network is the level of inhibition. DGCs modulate inhibition in the DG network through direct feedback and lateral inhibition (Freund and Buzsaki, in vitro and in awake-behaving animals.Even without the characterization of the functional connectivity with various targets of the local network, many groups have theorized that the role of adult-born neurons is to modulate the neuronal activity of the larger population of mature DGCs (Ming and Song, Neural synchrony is thought to be important for working memory, in which recently acquired information is held “on-line” for sustained periods of time (Durstewitz et al., If immature DGCs were recruiting feedback and lateral inhibitory circuits in the DG, we would expect that blocking neurogenesis may release inhibition and result in increased numbers of active DGCs. Burghardt et al.  found a Currently in the field of neurogenesis, there is ample data describing the cellular properties of adult-born neurons and recently there has been a fast-paced accumulation of data describing the functional role of adult-born neurons in memory behaviors. The gap in our knowledge is studies that integrate these two lines of study and that illuminate the functional role of adult-born DGCs at the network level. In this review we have focused on two possible roles that active adult-born DGCs might play in DG network computations, and we specifically considered the relationship of neurogenesis to sparse network coding. Immature DGCs could carry the message directly to the downstream CA3 region by being the sparse active members. Alternatively, they could impose the tone in the DG network through interactions with interneurons in the local circuit that mediate the maintenance of the sparse coding scheme and the selection of the appropriate DGCs, immature and mature, to carry the message (Sahay et al., Neurogenesis is an extraordinary plastic phenomenon that offers adaptive advantages to the DG due to the fact that it can be modulated by behavior and experience. Changes to the local dentate network as a result of experience can modulate the generation, survival, rate of maturation, and integration of adult-born DGCs (Piatti et al., The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Cholesterol granulomas are common in the mastoid antrum and air cells of the temporal bone. In the paranasal sinuses, especially in the frontal sinus, they have occasionally been mentioned in the literature. The pathogenesis is unknown, but the majority of the authors support the concept of airway obstruction in the cells well pneumatised of temporal bone and paranasal sinuses. The authors report a case of cholesterol granuloma of the frontal sinus treated with radical surgical techniques, and they also recommend an endoscopic approach to frontal sinus to restore or enlarge the nose-frontal canal and promote drainage and ventilation of the frontal sinus. The cholesterol granuloma is a histological entity consisting of granulation tissue in which large quantity of cholesterol crystals provoke foreign body giant cell formation –6. The pCholesterol granuloma is common in the mastoid antrum and air cells of the temporal bone . It has We report a case of cholesterol granuloma of the frontal sinus. The tumor is treated with radical surgical techniques, but we also recommend an endoscopic approach to frontal sinus to restore or enlarge the nose-frontal canal and promote drainage and ventilation of the frontal sinus. An 82-year-old male was referred to our attention with a two-year history of gradually enlarging swelling of the left brow. On examination, the swelling appeared soft and floating, 3-4 cm large, painless, and was not associated with diplopia and any ocular symptoms. On additional detailed anamnesis there was history of rhinitis with nasal obstruction and nasal discharge; there was no story of trauma. Nasal endoscopy demonstrated bilateral enlarged inferior turbinates.Computed Tomography (CT scan) of the orbits showed complete opacity of the left frontal sinus and partial opacification of contralateral frontal sinus and maxillary and ethmoidal sinuses. The opacification of the left frontal sinus appeared to be due to dense material without contrast enhancement which extended into the orbit through anterolateral (20 × 30 mm) and inferior (13 mm) breach of the sinus . ThroughClassically, the cholesterol granuloma is found in the petrous apex and other pneumatised areas of the temporal bone and paranasal sinuses. The pathogenesis is unknown, but many authors suggest that the key factors are prolonged inflammation and obstruction of a bony cavity that is normally aerated. Leon et al. suggested that the increased intrasinus pressure due to drainage obstruction may affect the venous and lymphatic drainage from the sinus cavity and cause the rupture of blood vessels and hemorrhage . In thisCholesterol granuloma of the frontal sinus is uncommon. Our MIDLINE literature search on “cholesterol granuloma of the frontal sinus” has reflected the rarity of this condition. Butler and Grossenbacher  and HellThe case reported by us was treated with radical surgical techniques and with an endoscopic approach to frontal sinus to restore or enlarge the nose-frontal canal and promote drainage and ventilation of the frontal sinus. 12–18-month followup shows no clinical signs of recurrence .


The genetic information in eukaryotic cells is organized in a specific structure called chromatin. The basic unit of chromatin is the nucleosome, which consist of four histone proteins and ~147 bp of DNA . Experim


Metabolomics is a part of systems biology dealing with the determination of qualitative and quantitative profile of low molecular weight compounds (metabolites) present in body fluids and tissues of living organisms. Metabolic composition is strongly dependent on the state of homeostasis and any deregulation should affect it. For this reason, there is now increased interest in metabolomics as a potential tool to support cancer research. At the same time the analysis of metabolic pathways involved in the process of carcinogenesis provides the possibility of a more complete understanding of the mechanisms that are critical for tumour biology.In this study, 1H NMR measurements were performed for thyroid tumour tissue and healthy tissue homogenates and analyzed by chemometric manner. Multivariate analysis of the data using the PCA, PLS-DA and OPLS-DA methods allowed a precise separation from normal thyroid tissue of all tumours originating in both benign and malignant lesions. In addition, classification of nodular goiter, follicular adenoma and malignant tumours was possible with comparable efficacy.


The introduction of HAART has considerably improved life expectancy and quality of life of people living with HIV/AIDS (PLWHA).If in the first years HIV infection was considered an absolute contraindication to implantology, it is now possible to employ implants positioning which allows a more complete functional and aesthetic rehabilitation of the oral cavity also in these patients; howewer there is still fear and prejudice in using this technique in PLWHA.We present the experience of Department of Dentistry of Luigi Sacco Hospital of Milan in over twenty years of implant surgery to evaluate the possibility of using implantology techniques in PLWHA without exposing them to greater risks of developing infections both during and after surgical intervention.The study considers a consecutive series of 21 HIV-positive patients  and 91 HIV-negative patients as control group , treated in the dental clinic of the Luigi SaccoHospitalfrom 1998 to december 2011.The pre-surgery phase included a collection of anamnesis, clinical examination data, diagnostic radiology evaluation and assessment of blood tests.We used the surgical technique of submerged fixture implants and mobile and fixed prostheses for the final prosthetic rehabilitation.Several failures occurred in both groups and were attributable to local factors related to receiving bone or to exceedingly invasive surgical techniques.We detected no lesions in the oral cavity in these subjects concomitant with the plants loss nor changes in their overall health conditions.Patients enrolled in this study presented both functional and aesthetic dental problems.The comparison between the success/failure rates in the two groups shows that implant surgery can be employed without risk for the patient and with success rate comparable to the general population, nevertheless it is important to assess the level of immune competence of the patient.Finally, the prosthetic rehabilitation of the oral cavity, in addition to the clear local benefit, has an important psychological effect on patients and on your quality of life.