The AJCC cancer staging atlas is the official publication of the American Joint Committee on Cancer, the world's foremost authority on cancer staging information.This is the first edition of this book, created as a compendium to the AJCC Cancer Staging Manual and Handbook, now in their sixth editions.This is an impressive and extremely valuable small book, which is easily transportable due to its small size, 20 × 12.5 cm (Figure It contains over 400 illustrations to facilitate an understanding for the stage of a tumour, and can easily be referenced for individual patients. Each chapter is extremely detailed, and indexed at the page margin, so one can easily access the pertinent chapter in this way rather than going to the index or table of contents each time Figure .The atlas is divided into eight parts, covering all the major systems/sites of cancer, with an introductory chapter on the principles and purposes of staging. It is packed full of useful illustrations.One of the most useful aspects of this atlas is the summary of changes for staging at the beginning of each system chapter Figure .I would recommend this publication to all health care professionals actively involved in the treatment of cancer patients, as the illustrations and text make the concept of the disease and its staging very simple to understand. It would also appeal to research students and post-doctoral scientists.From a training perspective, the book is probably more suited to postgraduate oncology or surgery trainees.


Accurate staging of rectal cancer is essential for selecting patients who can undergo sphincter-preserving surgery.  It may also identify patients who could benefit from neoadjuvant therapy. Clinical staging is usually accomplished using a combination of physical examination, CT scanning, MRI and endoscopic ultrasound (EUS). Transrectal EUS is increasingly being used for locoregional staging of rectal cancer. The accuracy of EUS for the T staging of rectal carcinoma ranges from 80-95% compared with CT (65-75%) and MR imaging (75-85%). In comparison to CT, EUS can potentially upstage patients, making them eligible for neoadjuvant treatment. The accuracy to determine metastatic nodal involvement by EUS is approximately 70-75% compared with CT (55-65%) and MR imaging (60-70%). EUS guided FNA may be beneficial in patients who appear to have early T stage disease and suspicious peri-iliac lymphadenopathy to exclude metastatic disease. Approximately 41,000 new cases of rectal cancer will be diagnosed in the year 2006 with an estimated 8,500 deaths . In thesCurrently available methods for assessment of rectal tumors include digital rectal examination, rigid proctoscopy, computer tomography (CT) scan, magnetic resonance imaging (MRI), and endorectal ultrasound (EUS). Digital examination allows for assessment of size and degree of fixation of rectal tumors. It has limited value because of its subjective nature and dependence on the examiner's experience . Rigid pTransrectal endoscopic ultrasound has emerged as the diagnostic modality of choice for clinical staging of rectal tumors. Because EUS can delineate the layers of the rectal wall -14, it iThe most widely used EUS endoscopes are available in two different designs: radial and curved linear array. Radial echoendoscopes produce a 360° image in a plane perpendicular to the long axis of the endoscope's insertion tube. Linear devices, on the other hand, produce sector-shaped images in a plane parallel to the long axis of the insertion tube. Linear imaging is used for interventional EUS-fine needle aspiration (FNA). EUS sonographic layers of the wall of the GI tract have been correlated to histopathological layers in several studies . The staPatients who undergo rectal EUS should receive an oral lavage preparation used typically consisting of polyethylene glycol electrolyte solution. Tumor staging and lymph node detection is performed by filling the echoendoscope ultrasound balloon with water, advancing the scope above the tumor and slowly withdrawing to the anal sphincters. The depth of wall invasion, invasion into the perirectal fat or adjacent organs, and presence of perirectal lymph nodes are carefully assessed Figure . If a noPrognosis of rectal cancer depends on its local, nodal, and distant tumor status. Rectal cancer is staged using the Tumor-Node-Metastasis (TNM) staging system, which is similar to colon cancer Table . Rectal One of the limitations of EUS is the under-staging of T3 tumors, which is caused by the inability to detect microscopic cancer infiltration owing to the limits its resolution. Other factors influencing the accuracy of tumor staging are operator experience ,21,22 anThe accuracy to determine metastatic nodal involvement by EUS is approximately 70–75% ,19,28 coet al evaluated the role of EUS-guided FNA of perirectal lymph nodes in the preoperative assessment of a cohort of 80 patients with newly diagnosed, nonmetastatic rectal cancer [EUS-guided FNA does not improve the preoperative staging of rectal cancer in most patients. Harewood l cancer . The oveThe overall accuracy of EUS, CT scan and MRI in the staging rectal cancer compared with surgical pathology is summarized in table The routine utilization of EUS for assessment and determination of tumor penetration into the bowel wall is essential for rectal cancer. This has become the standard of care as it allows for identification of patients in whom to administer preoperative neoadjuvant therapy . AnalysiAccuracy of EUS for staging rectal cancer after radiation therapy is decreased markedly due to post-radiation edema, inflammation, necrosis, and fibrosis. Studies suggest that the T-stage accuracy after radiation is 50%, with a 40% overstaging rate ,34. LympLocal recurrence rate after surgery alone for advanced rectal cancer is approximately 25% and decreases to 10% after radiation . The risThe use of preoperative EUS is an accurate modality for clinical staging of rectal cancer to guide neoadjuvant treatment. EUS guided-FNA may be beneficial in patients who appear to have early T stage disease and suspicious peri-iliac lymphadenopathy. Whether the accurate staging ability of EUS and EUS guided-FNA translates into improved outcomes in terms of reduced recurrence rates and ultimately prolonged survival remains uncertain. At this juncture, the utility of FNA-guided needle aspiration for evaluation of metastatic disease remains unclear.The author(s) declare that they have no competing interests.AAS conceived of the idea of the review article, and helped to draft the manuscript. YF helped to draft the manuscript. SH coordinated and helped to draft the manuscript. All authors read and approved the final manuscript.


Caspases belong to a class of cysteine proteases which function as critical effectors in apoptosis and inflammation by cleaving substrates immediately after unique sites. Prediction of such cleavage sites will complement structural and functional studies on substrates cleavage as well as discovery of new substrates. Recently, different computational methods have been developed to predict the cleavage sites of caspase substrates with varying degrees of success. As the support vector machines (SVM) algorithm has been shown to be useful in several biological classification problems, we have implemented an SVM-based method to investigate its applicability to this domain.1' and P2' amino acids and (iii) the tetrapeptide cleavage sites with ten additional upstream and downstream flanking sequences (where available) were tested. The SVM method achieved an accuracy ranging from 81.25% to 97.92% on independent test sets. The SVM method successfully predicted the cleavage of a novel caspase substrate and its mutants.A set of unique caspase substrates cleavage sites were obtained from literature and used for evaluating the SVM method. Datasets containing (i) the tetrapeptide cleavage sites, (ii) the tetrapeptide cleavage sites, augmented by two adjacent residues, PThis study presents an SVM approach for predicting caspase substrate cleavage sites based on the cleavage sites and the downstream and upstream flanking sequences. The method shows an improvement over existing methods and may be useful for predicting hitherto undiscovered cleavage sites. These results suggest that the SVM trained with the (-D) datasets may be useful for identifying hitherto undiscovered cleavage sites while circumventing the problem of overtraining due to the high percentage of "XXXD" cleavage sites in the training datasets. The results also provided further evidence for the suggestion that the P1', P2' and residues further upstream and downstream of the cleavage site may influence substrate cleavage, and by accounting for these flanking sequences, the SVM performance can be improved. It was also shown that the SVM method can be extended to predict cleavage sites with residues other than the canonical aspartate (D) at P1. While the occurrence of the non-canonical cleavage sites remains proportionately small, it does imply that the sampling space is not limited to the XXXD motif for cleavage sites. Consequently, the ability to predict these non-canonical cleavage sites will be a useful complement to existing computational methods which assumes the consensus XXXD motif as the basis for their algorithms.Our analysis on the training and test datasets indicated a large percentage of cleavage sites with the XXXD motif (~98%) and a very small percentage of cleavage sites with a non-canonical XXXE motif (~2%). While experimental cleavage site specificities reported in Thornberry XD motif , the inc4P1 training dataset alone. As the GraBCas method can only be applied to potential cleavage sites with aspartate (D) at the P1 position, we scored the positive sequences in the P4P1 training dataset with the GraBCas matrix values for the different caspases, selected the highest score and checked for the percentage of correctly predicted cleavage sites  against a series of cut-off scores. As shown in Table 4P1 test dataset. As there were no recommended cut-off scores for predicting the cleavage sites, we chose the cut-off score of 0.1, which was used for the granzyme B cleavage site prediction as reported in Backes et al.  and its mutant sequences as reported in Yan et al. , based o1' and P2' positions and further upstream and downstream of the cleavage site. In addition, the SVM method may be useful for predicting the non-canonical cleavage sites lacking aspartate (D) at the P1 position, such as those found in DIAP1 and other proteins as reported in literature  and cysteine as . Therefore, for the P4P1 dataset, each sequence was represented by an 80-dimensional vector. Sequences in the P4P2' and P14P10' datasets were represented by 120 and 480 dimensional vectors respectively.To encapsulate the sequence information into a format suitable for SVM training and testing, the sequences were transformed into xi  with corresponding labels yi ∈ {+1,-1}. To classify the data, the SVM trains a classifier by mapping the input samples, using a kernel function in most cases, onto a high-dimensional space, and then seeking a separating hyperplane that differentiates the two classes with maximal margin and minimal error. The decision function for new predictions on unseen examples is given as:For SVM implementation, we used the freely downloadable LIBSVM package by Chang and Lin . DetailsK (xi·xj ) is the kernel function, and the parameters are determined by maximizing the following:where under the conditions,C serves as the regularization parameter that controls the trade-off between margin and classification error. As the efficacy of the SVM prediction system is dependent on the type of kernel used, we explored various kernels  commonly implemented in biological problems on our datasets. We have chosen the widely used radial basis function (RBF) kernel as it was found to be most effective (data not shown):The variable γ, which determines the capacity of the RBF kernel and the regularization parameter C.Two parameters are required for optimizing the SVM classifier; γ and C, we applied 10-fold cross-validation on each of the training datasets using various combinations of γ and C. In 10-fold cross-validation, the training dataset was spilt into 10 subsets where one of the subsets was used as the test set while the other subsets were used for training the classifier. The trained classifier was tested using the test set. The process is repeated 10 times using a different subset for testing, hence ensuring that all subsets are used for both training and testing. SVM parameters γ and C were stepped through combinations of 0.01, 0.1, 1, 10, 100 for γ, and 1, 10, 100 and 1000 for C in a grid-based manner.To optimize the SVM parameters γ and C obtained from the optimization process were used for training the SVM classifier using the entire training dataset. The SVM classifier was subsequently used to predict the test datasets. Various quantitative variables were obtained to measure the effectiveness of the SVM method:The best combinations of TP, true positives – the number of correctly classified cleavage sites.(i) FP, false positives – the number of incorrectly classified non-cleavage sites.(ii) TN, true negatives – the number of correctly classified non-cleavage sites.(iii) FN, false negatives – the number of incorrectly classified cleavage sites.(iv) Sensitivity (SE) and Specificity (SP), which indicates the ability of the prediction system to correctly classify the cleavage and non-cleavage sites respectively, were calculated:Using the variables above, a series of statistical metrics were computed to measure the effectiveness of the SVM method. Accuracy (AC), for the percentage of correctly classified sites, and the Matthews Correlation Coefficient (MCC).To provide an indication of the overall performance of the system, we computed 14P10' (-D) dataset  was used to predict the cleavage of Livin [Swiss-Prot:Q96CA5] and the various deletion mutants, based on the prediction of the caspase cleavage sites, as reported in Yan et al. [1 residue of the reported Livin cleavage site (DHVD52) were extracted from both wild type and mutant Livin sequences. Mutants used in this study are: LE Δ52–61, Δ53–55, Δ55–57, Δ57–59, Δ60–62, Δ52–61, Δ53–61, Δ52 and Δ51–53. In mutants with Asp-52 deleted, the peptide windows were centred on the subsequent residue occupying position 52.The SVM trained using the Pn et al. . 24 amin4-P3-P2, and assume that P1 is an Asp (D) residue, the GraBCas matrices were used to score only the positive sequences (cleavage sites) from the P4P1 training dataset. As GraBCas scores for different caspases were available, only the highest scores were recorded. The percentage of correctly predicted cleavage sites  were calculated as mentioned earlier. The P4P1 test dataset was tested in the similar manner and the SE score was obtained at a GraBCas cut-off of 0.1.As the CasPredictor method is unavailable from the published website, it was not tested. The performance of GrabCas was compared with the SVM method using the current datasets. As the GraBCas scoring matrices are specific for the tripeptide, PLJKW conceived the application of SVM for prediction of caspase substrate cleavage sites. TWT contributed with ideas on the experimentation and SR finalized the manuscript. All authors read and approved the final manuscript.Dataset of caspase substrate cleavage sites . List of caspase substrate cleavage sites used for cross-validation and training of the SVM.Click here for fileDataset of caspase substrate cleavage sites (for independent out-of-sample testing). List of caspase substrate cleavage sites used for independent out-of-sample testing of the SVM method.Click here for file


Synthetic glycolipids prepared by esterification of various sugars and sorbitol, and containing various numbers of saturated or unsaturated fatty acid residues as well as bacterial lipid A and lipopolysaccharide, were tested for mitogenicity of splenic cells of Fischer rats and Swiss mice and for the augmentation of humoral immune response against sheep red blood cells in these species. Subsequently a few of the humoral immune-response-enhancing glycolipids were compared with non-enhancers in their anti-tumour activity against 13762 rat mammary carcinoma in inbred Fischer 344 rats and Ehrlich tumour in Swiss mice. They were given systemically after tumour inoculation and intratumourally in squalene and Tween emulsion after intradermal MAC tumour development. It was observed that certain structural characteristics in glycolipids with respect to the type of sugar, the type and number of fatty-acid residues were needed for their adjuvant action of the humoral arm of the immune response. Although humoral immune-response enhancers were somewhat superior to non-enhancers in their anti-tumour activity, the correlation coefficient demonstrated a lack of significant concordance. It is concluded that glycolipids selected for their ability to augment humoral immune responses against standard antigens need not be suspect as tumour-enhancers on the grounds that they would elicit blocking antibodies in vivo against tumour-associated antigens.


For eliminating the unexpected decoherence effect in cavity quantum electrodynamics (cavity QED), the transfer function of Rabi oscillation is derived theoretically using optical Bloch equations. In particular, the decoherence in cavity QED from the atomic spontaneous emission is especially considered. A feedback control strategy is proposed to preserve the coherence through Rabi oscillation stabilization. In the scheme, a classical quantum feedback channel for the quantum information acquisition is constructed via the quantum tomography technology, and a compensation system based on the root locus theory is put forward to suppress the atomic spontaneous emission and the associated decoherence. The simulation results have proved its effectiveness and superiority for the coherence preservation. The enormous potential of quantum information has caused the widespread concern in the scientific community and has become an important research focus. Among the implementation of hardware design for quantum computing such as cavity QED, ion trap, nuclear magnetic resonance, quantum dots, and superconducting systems , cavity However, all the advantages in cavity QED depend on the coherence of the system. The loss of coherence in quantum mechanical superposition states limits the time for which quantum information remains useful. Similarly, it limits the distance over which quantum information can be transmitted . Hence, g) is proportional both to the dipole moment of the atom and to the electric field of the photon at the atom's location.The cavity QED investigates the interaction of single atoms with single electromagnetic field modes, defined, for example, by a pair of mirrors illustrated in g) is larger than the dissipation arising from the loss of photons (at rate κ) or from emission from the atom into other modes at rate γ, that is, g ≫ κ, γ. The excited atoms will periodically release and absorb photons with a certain frequency, a phenomenon known as vacuum Rabi oscillations ′ in the case of resonant light ω = ω0, the optical Bloch equation degenerates into constant coefficient differential equations [ρ11 = ρ11*, ρ22 = ρ22*, we can give a general solution of ρ22:For the special initial conditions quations :(10)dWhen external coherent laser field was applied, the vacuum-field-induced coherence effects will be replaced by the microwave-field-induced coherence effects. The decoherence effect caused by spontaneous emission in the system can be suppressed by the introduction of the control of the laser field. Furthermore, the method for implementing the decoherence suppression is to change the Rabi oscillation frequency. According to the previous strategy, the transfer function of the system is constructed and then the decoherence suppression is realized through the compensation of the transfer function.ξ < 1):We can infer from  that theHence, the unit step response of the open-loop system described by  is as foComparing formula  and 14)14), the s = −p in the negative half real axis, where p > ξωn. After this step, the root locus of the system is as Add a pole s = −z to locate the asymptotes of the root locus in the right side of the imaginary axis. Let Δx > 0 be the intersection of the asymptotes and the real axis. To meet the requirements of the asymptote (−p − 2ξωn + z)/2 = Δx, we get z = p +2ξωn + 2Δx, where Δx should be moderately selected to avoid causing the open-loop gain to be too large. After this step, the root locus of the system is as Considering that the compensated system is sensitive to the open-loop gain after step (1), then we add a zero If we put the open-loop transfer function  into a uAccording to the control theory, the closed-loop characteristic equation after the previous two steps iss = iy and inserting it into  in in16) inIn the feedback control of the quantum system, the information of the density matrix cannot be measured directly because of the characteristics of the quantum system. One of the challenges exists in how to access the quantum information and feed it back to the input, in other words, how to construct the negative feedback channel for the quantum second-order system. In our work, for solving the problem of information acquisition of the quantum state, a quantum tomography scheme is designed to reconstruct the density matrix.ρ is reconstructed from the output; thus, the quantum information has been transformed into classical information and fed back to the input. In order to realize the compensation strategy of the Rabi oscillation based on the transfer function analysis, a compensation circuit is designed using the active phase-lead compensator and the double integral A/D converter. The quantum density matrix information is transformed into the classical voltage signal for driving the light beam, which can be used to stabilize the Rabi oscillation. The details are described in Sections The physical implementation of the proposal is as N identical copies of the output photon pass through the horizontal-polarization wave plate, and record the number n0.Let the N identical copies of the output photon pass through the vertically polarization wave plate and record the number n1.Let the N identical copies of the output photon pass through the left-rotation wave plate and record the number n2.Let the N identical copies of the output photon pass through the right-rotation wave plate and record the number n3.Let the Quantum tomography technique is an indirect method to determine quantum system parameters. The basic idea is to construct multiple copies of the photon from the system output and determine density matrix elements of the output photon through the optical operations of the photon copies . Assuminni   and the system output ρout can be described as follows [The relationship between  follows , 12::The density matrix of output photon can be reconstructed according to  = (s + z)/(s + p), (p > z), the implementation of the active phase-lead compensation network is as Due to the typical phase-lead compensation Ω|2 in the expression of K′, a double integral A/D converter can be used to realize the reciprocal operation of |Ω|2 as Due to the 1/|If the element ucted by , a voltaThrough the previous analysis, a coherence preserving solution in cavity QED has been presented using the quantum tomography and the Rabi oscillation compensation. In the following, simulation results have been analyzed for the evaluation of the strategy.As stated in ni   can be calculated from  for calculating the output density matrix by  = 1,  ρ22(0) = 0). The probability to find the atom in the excited state is plotted for various ratios of γ and the Rabi frequency Ω. In the simulation, we have chosen the following value: γ = 0,  γ = 0.1Ω,  γ = 0.25Ω,  γ = 0.5Ω, and γ = Ω.From the discussion in γ = 0, the oscillation is with equal amplitude and fixed frequency. With the γ increasing, the damping effect becomes more and more significant. The main objective of our design is to overcome the damping effect by compensation; that is to say, when γ which stands for the spontaneous emission exists, the process will still be a coherent process with equal amplitude and fixed frequency.As can be seen from γ = 0.3, |Ω | = 2, p = 1.5, and Δx = 0.1, the unit step response of the uncompensated and compensated system is shown in Figures According to the strategy described in It is clear that the uncompensated system approaches a constant value after the damping process and the compensated system can maintain a sustained oscillation with a constant frequency and amplitude, which have proved the effectiveness and superiority of our design.For the coherence preservation in cavity QED, the model of the damping Rabi oscillation in the form of the transfer function is derived based on the optical Bloch equation. The transfer function of the damping Rabi oscillation is compensated using the root locus technique derived from the classical control theory to suppress the atom's spontaneous emission. Finally, a physical implementation is put forward to keep the coherence in cavity QED. The strategy has provided a basis for the entanglement preparation in cavity QED theoretically. The research has theoretical significance and practical value. The simulation results showed that the compensated system can maintain a sustained oscillation with a constant frequency and amplitude. And it means the process is a coherent reversible one, which is an ideal environment for quantum information processing.However, this work is based on the semiclassical optical Bloch equations. In other words, only the atom is quantized and the field is treated as a definite function of time rather than as an operator. To obtain more rigorous results, the further work will focus on the Jaynes-Cummings model, in which the radiation field is also quantized. And meanwhile, an appropriate quantum feedback channel  is expec


Lions Quest Skills for Adolescence as perceived by adolescents and teachers who took part in it. Lions Quest has become recognized as an evidence-based program for preventing alcohol and drug use through the development of social skills and the promotion of meaningful engagement in the school community (Lions Clubs International, Overview of Skills for Adolescence Lions Quest. Deductive and inductive analysis of interview transcripts clearly underscored that the positive perceptions of those early adolescents on the quality of their relationships with friends outweigh the negative impression that can be created by peer pressures at this age. It is through such a filter that these adolescents came to appreciate the impact of Lions Quest. Their need to be part of a circle of friends also comes to the fore as a crucial component of a sense of school belonging (Faircloth and Hamm (The purpose of this qualitative study is to pave the way for the establishment of healthy interpersonal relations by facilitating an understanding of the impacts of and Hamm  J Youth  Social workers must continually re-examine their roles and tasks based on a dual responsibility that consists of making decisions on solid findings, and evaluating the effects of their actions , risk and protective factors, and the sense of school belonging. We will describe the methodology by which we investigated the perspective of concerned actors. We will offer key findings showcasing the views of adolescents who participated in In the field of social prevention geared toward adolescent problem behaviors, research has seen numerous advances in recent decades Jenson . More prOn the other hand, programs that proved to be more successful sought to help adolescents to acquire social skills, make responsible decisions, develop higher self-esteem and resist negative peer pressures .Lions Quest seeks to prevent or delay adolescents’ alcohol and drug use by helping them to develop a constructive commitment to their family, school, and community through the development of social skills and competencies whereby they: (1) develop a capacity for self-assertion and for resisting negative peer pressures; (2) acquire a sense of responsibility; (3) develop conflict resolution skills; and (4) learn how to intervene with peers who start to become substance users. Through a series of 30 one-hour sessions, participants meet in classrooms during regular hours, typically during health or physical education periods. They are conducted by the teacher of the class involved, with occasional support offered by a social worker from the social services agency that initiated the project. In Eastern Ontario, the program brought together students primarily from Grade 7, with several from Grade 8, all between 12 and 14 years of age. This age group was the focus of evidence-based research conducted by Eisen et al.  was insecure. She often wanted to change schools. She had problems with other girls and got into arguments. She was turning in on herself. She decided to take the situation in hand. How did the program help her through these troubles? Certainly in the area of self-confidence, I was able to offer other tools, and this helped her to make appropriate decisions. (Teacher 1)This trait emerges as a dominant theme in the interviews held with school staff. The five teachers related—often and with enthusiasm—how important it is that young adolescents participating in Lions Quest helped the young adolescents to better assert themselves and defend their opinions. One teacher cited the case of a tall, strong boy who had been intimidating other students and, thanks to the program, was able to gain a healthy form of self-respect and to express himself in a more sociable fashion. The same teacher spoke as well of another boy who had been the scapegoat of his group but learned to speak up for himself. He was being picked on, all the time. Now it’s not like that any more because he can defend himself. He does it verbally, by saying, ‘Stop it, I don’t like this!’ (Teacher 1) According to the teachers, Lions Quest played a pivotal role in bringing about such changes. One said, It takes a lot of courage for some of them to take a stand outside of their group. (…) The discussion groups we conducted [through the Lions Quest program] gave them the confidence to speak up for their own beliefs, and they felt like, ‘Hey, this is how I feel, and I may be for or against something, but I’ve got my reasons and it’s OK if they’re different from others.’ I think the students developed their skills considerably. (Teacher 3)The interviews with teachers confirmed that He had a serious behavioral problem. While we were conducting the ‘Lions Quest’ program, there was a moment when everything clicked into place, and he changed. (…) He gives his all when he discusses something, by expressing himself with words instead of acting up when he’s mad. (Teacher 2) Another indicated that not only did the program help the teens to develop citizenship values through participating in voluntary activities; it became a drawing card through the interest it generated in civic spirit.The teachers also noticed a difference in relationships among the students under their daily supervision and offered several examples. One spoke of an aggressive boy who learned to verbalize feelings instead of making threatening gestures when angry. Lions Quest to issues that fall within the daily reality of 12- to 14-year-olds, to realize immediate results, and to see improvements in peer relationships among the students—this last point being a constant concern of young persons of that age group  But you know, by the end [of Lions Quest program], everybody was beginning to say: ‘You know what, she really is fun to be with, let’s go and hang out with her’. The relational dimension, notably ties among classmates and friends, was clearly placed center stage through the statements of the adolescents we met. They recounted that within the scope of Ever since ‘Lions Quest,’ after those activities you’d have to say there’s less bullying at school.  Although only a minority of students addressed the topic of atmosphere at school, these short yet thought-provoking comments leave the impression that the program indeed had an influence on the daily lives of many students and on the social climate within groups. We’re all close in our class, the whole 8th grade, we’re all one big family. (…) We don’t judge anybody (…) we’re always there for each other. (…) Someone’s accepted for who they are. It appears that the program activities had a favorable influence on cohesion within groups, a theme readily identifiable in the students’ comments. We found our class fun because the teacher was organizing lots of activities and we learned by doing fun things. Now we’re more confident in ourselves. The theme of confidence in oneself appears frequently from an analysis of the interviews with adolescents, mirroring much of what was revealed in the teacher interviews. A range of activities guided them toward recognizing their strengths and talents and feeling at ease about revealing these attributes to others. About his general impressions of the program, a 13-year-old boy answered without hesitation: Interviewer: ‘What is it that makes you have more respect now for your own opinions?’ The 13-year-old student responded: Probably because I’m more sure of myself. (…) And I know I have a good idea about what I’m doing.  These new capabilities inspired the students to surpass themselves. I was starting to flunk math and French. (…) I wanted to get some help even if maybe they’d laugh at me, so I took the risk anyway.  It became apparent that the adolescents drew much from Lion Quest in terms of life lessons given that it presented them with strategies for better self-expression while respecting others at the same time. As for process, although the manner whereby the strategies were applied in some cases did not achieve the desired level of maturity, they nonetheless generated a higher degree of self-awareness. I usually don’t say it in the well-behaved manner that everybody says you should. I usually use a loud voice. We used to have all these programs where it’s, like, telling you how to solve these conflicts and it was always, take time to calm down and then express it to the person calmly. According to the adolescents interviewed, growth in self-confidence goes hand in hand with an increase in self-assertion. (…) I try to solve the problem, then find out what I’m doing that he doesn’t like, because I don’t wanna lose my friend.  Indeed, the influence of Lions Quest in the area of conflict resolution was moderated according to the individual teens being interviewed. Some said they would react in the same fashion if a similar conflict situation presented itself, whereas others attested that Lions Quest played a role in improving their conflict resolution skills. I wasn’t thinking about what I was saying, so just about anything came out, but now I know how others feel if I let loose like that. I’ve learned to be nice. I’ve decided I should think before I speak. The perceptions of the students indicated they also developed certain skills in conflict resolution, their comments indicating that such ability is often tied in with relationships with peers. They gave numerous examples of previous conflicts they had experienced with classmates, including disputes between friends and incidents of bullying. They related anecdotes about how they learned to calm down and better resolve discord, seek the advice of an adult, reach a compromise through discussion, as well as apologize. Primarily what the students from all three schools retained from the program were the elements calling for reflection upon their relationships with friends. In this angle, their perspectives follow the same direction as those of their teachers. It has become common that the peer group occupies such a predominant place in adolescent life that, in the case of 12- to 14-year-olds, it surpasses that of parents, from whom the offspring strive to distance themselves in order to shape their own identity  These statements clearly fall in line with the research of Faircloth and Hamm The teens discussed during the interviews that the frequency of social contacts was an important aspect of the stability of their friendships: seeing their closest friends often at school, during extracurricular activities, or outside the school altogether. These adolescents insisted on the qualities they considered to be important in their peers, specifying repeatedly they sought friends who were of respectful character. As an example, one 14-year-old girl stated, It’s cool because the whole gang’s like me, and I’m the same as them. We like everybody a lot, we have fun together, we’re all smart the same way I am and we’re really close. We’re a family. In the same vein, those adolescents appreciate being able to feel at ease in their immediate environment, thereby benefiting from a freedom from intimidation. Many of them indicated that they and their peers accept and respect differences among themselves, and are thus able to spend time together in their group dynamic in a spirit of mutual understanding. To quote one 14-year-old boy, . I can tell him something and he won’t turn around and blab it all around. And he can tell me stuff too, like give me his opinions and I tell him mine.  A large number of teens reinforced the viewpoint that a circle of friends provides mutual support. They stressed the fact that young people need to provide a positive social network and underscored the importance of looking out for each other’s welfare. They cited many examples whereby a friend who was living through a difficult situation or experiencing negative emotions received support from the others whose presence brought comfort, distraction, or much-needed laughter. These findings flesh out the conviction that such mutual assistance and acceptance among peers is the foundation of a positive social network.Apart from that well-being, the young adolescents place considerable value upon trust in relationships. It is important to be able to open up to their friends and have their privacy respected. Many affirmed that they share secrets with trusted friends and in return are taken into similar confidence on a one-for-one basisLions Quest), complement social work interventions with young adolescents, and provide the guideposts leading to social norms and a more profound understanding of their daily life experiences.In essence, respect, trust in each other, and mutual support are the fine points that young adolescents hold in high regard among their friends. When these traits bind a group of friends, they lead to shared ties through participation in activities. In this regard, Brown and Larson  specify Lions Quest on 12- to 14-year-olds, as well as to determine whether any aspects of their sense of school belonging contributed to the achievement of the actual program objectives. The verbatim indicate that, beyond the expected capacity to resist peer pressures as originally set forth by the program, the development of social skills and engagement to their school community that the young adolescents carried forth from this exercise encouraged them to think about the quality of their relationships with friends, and even more so, to improve them. Interestingly, they listened more attentively when adults addressed this issue that they considered to be crucial in the context of their own frame of reference and their day-to-day experiences. We therefore come face to face with their need to be part of a milieu, of a niche finding and of a circle of friends, the latter having moved to the forefront as a crucial component of a sense of school belonging  have a tangible affiliation with members of that group; (2) benefit from a feeling of self-esteem stemming from involvement with the group; and (3) believe that they are appreciated by the other members and take pride therein , the young adolescents in this study entered into a phase of reflection vis-à-vis Notwithstanding all these considerations, it should be specified that even when adolescents experience well-being thanks to supportive friends, such benefits can be compromised if the support offered by adults is weak, even more so if the younger ones are passing through a time of personal difficulty (Buchanan and Bowen Lions Quest, they were becoming a valued part of a larger “whole” with talent, potential, and ventures to pursue. In their comments, they enshrined what researchers in social prevention advance: get involved in a positive fashion at least at school; develop skills and solid ties; and benefit from encouraging positive reinforcement from various actions within one’s environment, from positive friends and prosocial adults (Brooks To conclude, these young adolescents had begun to feel that, through s Brooks . The perLions Quest program aims to prevent or delay adolescents’ alcohol and drug use by helping them to develop a constructive engagement in their school community through the development of social skills and competencies. The study offers distinctive insights from the perspective of those concerned by the implementation of the program in question. Nevertheless, it would be interesting to conduct a longitudinal study to assess the effect of Lions Quest over time.This study sought to bring about an understanding of the influence of participation in a program geared toward the positive development of adolescents. The As established earlier, there is little or no research calling for more studies that focus on the views of young adolescents. In fact, we propose that it is logical, and perhaps imperative, to consider the views of the very individuals for whom interventions are developed and implemented (Gallé and Lingard


The only anatomical variation of the superior turbinate defined in the literature is concha bullosa. Determination of anatomical variations of the intranasal structures is important to perform safe endoscopic sinus surgery and avoid complications.We report a case of an unusual anatomical variation of the superior turbinate in a 55-year-old Turkish man with nasal obstruction and headache.Anatomical variations of superior turbinate are very rare. Variations of intranasal structures can easily be detected with coronal plane paranasal sinus computed tomography. Although there are many anatomical variations in the nasal cavity, those related to the superior turbinate are extremely rare. The only variation of the superior turbinate defined in the literature so far is concha bullosa. The determination of anatomical variations in the superior nasal cavity is very important to perform safe endoscopic sinus surgery and avoid complications. Anatomical variations in this region can sometimes cause significant sinonasal symptoms such as nasal obstruction, smell disorders and migraine-like headache. Only a coronal plane paranasal sinus computed tomography (CT) provides detailed information about this inaccessible area of the superior nasal cavity. Therefore, careful evaluation of a paranasal sinus CT scan before surgery is very important in these cases. Here we report a case of unusual anatomical variation of the superior turbinate in a 55-year-old Turkish man.A 55-year-old Turkish man was admitted to our clinic with complaints of nasal obstruction and headache lasting for years. There was a nasal mass in front of his left middle turbinate extending nearly down to the inferior turbinate in anterior rhinoscopic examination which had an unclear origin. The endoscopic examination revealed a mass extending from his superior nasal cavity toward his inferior turbinate on the left side. The opposite nasal cavity was obstructed by the deviated septum. As shown in Figures Nasal obstruction and headache are common complaints of patients presenting to otorhinolaryngology clinics. Nasal septal deviation and unilateral nasal masses are two common causes of nasal obstruction. The differential diagnosis of unilateral nasal masses which may be congenital, inflammatory, neoplastic or traumatic is important and should be done thoroughly.The rhinogenic causes of headache are twofold. The first is acute rhinosinusitis and the second is any anatomic variation within the nose. These anatomic variations or anatomical abnormalities can cause headache in and of themselves or as a result of causing sinusitis because of blockage of the osteomeatal complex. These anatomic variations include deviated nasal septum, in particular a spur which may contact either the middle or inferior turbinate (this is the most common cause of rhinogenic headache); congestion of the turbinates; nasal neoplasm; pneumatized agger nasi cells; unusual deflections of uncinated process; paradoxically bent middle turbinate and variations of ethmoid bulla . PneumatChanges in turbinate skeletal structure or increased respiratory mucosa volume may constrict the nasal passage causing a negative effect on paranasal sinus ventilation and mucociliary cleaning of the middle meatus which is thought to play a role in the development of sinusitis .et al. [Christmas et al.  and Cleret al.  have sugAnomalies of the superior turbinate are very rare. Paranasal sinus CT can easily identify unusual anatomical variation of the superior turbinate which should be evaluated with great caution by otorhinolaryngologists and radiologists preoperatively.Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.CT: Computed tomographyThe authors declare that they have no competing interests.TS made the diagnosis and wrote the case report. EG reviewed and modified. BE supervised. All authors read and approved the final manuscript.


Pneumatization of the intranasal turbinates or concha bullosa is an anatomic variation of the lateral nasal wall. Concha bullosa is defined as the presence of air cells in turbinates. It can be best diagnosed with paranasal sinus computed tomography. Concha bullosa is a possible etiologic factor for recurrent sinusitis due to its negative effect on paranasal sinus ventilation and mucociliary clearance. Concha bullosa is most commonly seen in the middle turbinate and less frequently in the inferior or superior turbinate. Pneumatization of all turbinates is very rare. To our knowledge, there are only two publications about a case with concha bullosa in all turbinates in the current literature. Here, we present a woman with bilateral pneumatization in all three intranasal turbinates. Intranasal turbinates are required structures for the maintenance of normal nasal functions such as humidification, hydration, lubrication of the upper respiratory system, olfaction, filtration, and thermoregulation. The reason of pneumatization of the intranasal turbinates is still unknown. Although mostly asymptomatic, overpneumatized turbinates may constitute mass effect and in these cases as a result of impaired ventilation and drainage of osteomeatal region it can lead to sinusitis.A 20-year-old woman was admitted to our clinic with nasal obstruction, postnasal drip, and intermittent headache for 3 years.Anterior rhinoscopy and nasal endoscopic evaluation revealed that the nasal septum was deviated to the left, bilaterally inferior and middle conchae were hypertrophied, and the nasal mucosa was normal.Paranasal sinus computed tomography (CT) scan with coronal plane views revealed that the inferior, middle, and superior turbinates were pneumatised bilaterally, a moderate nasal septum deviation to the left with a spur formation and inflammatory mucosal thickening in the right maxillary sinus Figures  and 2.After giving information to the patient about the surgical procedure we performed an endoscopic surgery including lateral marsupialisation for both middle turbinate pneumatizations, a limited septoplasty and crushing and outfracture of the inferior turbinates. For both inferior turbinate pneumatizations, the bullous structures were reduced by crushing and outfracture. Superior turbinates were left intact since they had no visible clinical significance. She was discharged from the hospital 1 day after the operation and any postoperative complications were not seen. Follow-up evaluation indicated that the patient's symptoms had improved dramatically and she had no further complaints.Concha bullosa (CB) is the most common anatomical variation of the osteomeatal complex region. Its incidence has been reported between 13% and 53% . The devAlthough the majority is asymptomatic, due to its negative effect on paranasal sinus ventilation and mucociliary cleaning of the middle meatus, CB can cause the development of maxillary or ethmoidal sinusitis. The severity of symptoms resulting from CB is closely associated with the degree of pneumatization.The difference between a hypertrophied turbinate and its pneumatization can be only distinguished by paranasal sinus CT. In our patient, the anterior rhinoscopic and endoscopic views of the nasal cavity were not distinctive for pneumatization of the turbinates, but paranasal sinus CT imaging allowed us to diagnose the pathology. To our knowledge, there have been two reports about a case with CB in all turbinates , 5. We pThe treatment of CB is endoscopic partial middle turbinate resection. With the widespread use of imaging techniques such as CT have provided us with detailed information of nasal cavity and paranasal sinuses. This helps the surgeons be aware of the anatomic variations regarding the osteomeatal complex region. Surgical resection of CB during endoscopic sinus surgery requires careful protection of medial lamella and resection of only lateral half of turbinate. The extent of turbinate pneumatization is evaluated on paranasal sinus CT scans and this allows the surgeon to anticipate points of safe entry into the lumen of CB. Careful evaluation of paranasal sinus CT scans before surgery is important in these cases.Bilateral triple CB is very rare anatomical variation. The presence of such anatomical variations regarding intranasal nasal turbinates can lead to complications during endoscopic sinus surgery. The anatomical variations of the intranasal turbinates can be determined with paranasal sinus CT. Therefore, it is especially important that otolaryngologists and radiologists are well aware of such anatomical variations of osteomeatal complex region when evaluating patients with sinonasal symptoms.


PTPN22 C1858T polymorphism and the risk of endometriosis. To evaluate  A meta-analysis of 10 published case-control studies (from four articles), with a total sample of 971 cases and 1,181 controls, was performed. We estimated risk  of endometriosis associations with the C1858T polymorphism. A significant increased risk in all genetic models of the variant T allele with endometriosis  was found. The analysis without the study whose controls deviated from the Hardy-Weinberg equilibrium exacerbated these effects in the homozygous and recessive models . In the Italian subgroup, a significant risk association was found in the homozygous and recessive models .PTPN22 (C1858T) and the risk of endometriosis suggest this polymorphism might be a useful susceptibility marker for this disease. The associations observed between  It presents multisystem involvement affecting several organs, most commonly in the peritoneum and pelvis, especially the ovaries, and less often in the recto-vaginal septum.2 This results in pelvic pain, dysmenorrhea, and infertility.3Endometriosis is a condition in which a tissue that is histologically similar to the endometrium, with glands and/or stroma, grows outside the uterine cavity.Numerous hypotheses have already been put forward to explain the presence of ectopic endometrial tissue and stroma. However, none of them could explain all implantation sites and symptoms, leading researchers to search for new theories which alone or together with the hypotheses already proposed could better explain the etiology of endometriosis.5Exposure to estrogen is one of the major endocrine risk factors for endometriosis. In contrast, progesterone is somehow protective against the development of endometriosis, for disrupting the production of local differentiation factors necessary for the regulation of the expression of responsible genes, promoting the ability of refluxed menstrual endometrial fragments to invade the peritoneal surface, interfere in vessels, and establish endometriosis. Because of the powerful anti-inflammatory effect of progesterone, reduced sensitivity to this steroid could contribute to the autoimmune nature of endometriosis.7In this context, hypotheses addressing immunological predispositions as well as genetic factors have been considered,8 and polymorphisms in genes associated with autoimmune diseases have emerged as possible candidates for endometriosis development.4Although the etiology of autoimmune diseases is unknown, they are characterized by genetic and environmental factors in their development. Just as in autoimmune diseases, in endometriosis similar immunologic alterations occur, such as an increase in the number and cytotoxicity of macrophages, polyclonal increase in the activity of B lymphocytes, abnormalities in the functions and concentrations of B- and T-lymphocytes, and reduction in the number or the activity of natural killer cells. Furthermore, the presence of specific antiendometrial and antiovary antibodies has been found both in endometriosis and infertility.PTPN22) gene, located on 1p13.3-13.1, and it is involved in the regulation of T-cell receptor signaling.9The PTPN22 gene shows a missense single-nucleotide polymorphism at nucleotide 1858 (C>T), which causes a substitution of an arginine at codon 620 (CGG) for a tryptophan (TGG) (W620 variant) associated with autoimmune disorders.10 The variant does not bind kinases well and appears to encode a gain-of-function enzyme, which has been suggested to increase the inhibition of T-cell-receptor signaling, affecting thymic deletion of autoreactive T-cells or the development or function of peripheral regulatory T-cells.12Lyp is a protein tyrosine phosphatase encoded by non-receptor 22 .17 was used to assess the methodological quality of the studies included. These studies were judged based on three broad perspectives: selection, comparability, and exposure (case-control studies) or outcome (cohort studies), by a ‘star’ rating system with a score ranging from zero star (worst) to nine stars (best). A score of seven stars or greater indicated that one study was of high quality.The Newcastle-Ottawa Score (NOS) quality assessment scaleversus TC + CC genotypes as well as the TT + TC versus CC genotypes. These contrasts correspond to recessive and dominant effects of the T allele. To compare effects on the same baseline, we used raw data for genotype frequencies to calculate study-specific estimates of the OR. Pooled ORs were obtained using either the fixed18 (in the absence of heterogeneity) or random19 (in its presence) effects models. Heterogeneity between studies was addressed in a number of ways. First, it was estimated using the χ2 based Q test.20 Recognizing the low power of this test,21 significance threshold was set at p=0.10. Second, it was explored using subgroup analysis20 with population as variable. And third, it was quantified with the I2statistic, which measures the degree of inconsistency among studies.21 Sensitivity analysis, which involved omitting one study at a time and recalculating the pooled OR, was also used to test for robustness of the summary effects. Significance was set at a p value of ≤0.05 throughout, except in heterogeneity estimation.Data were analyzed using Review Manager 5.1 . We estimated the odds ratio (OR) of association with the variant TT genotype compared with the wild-type CC genotype. To evaluate importance of the heterozygous genotype, dominant and recessive genetic models were also applied. Thus, we examined contrast of TT 13 had zero homozygous and recessive datasets in cases and controls, which rendered them non-estimable, hence the total number of studies was nine for these genetic models. When the number of studies is lower than ten,22 qualitative and quantitative tests for publication bias become less sensitive, obviating investigation of publication bias. Non-zero data in the dominant and co-dominant models placed the overall total number of studies at 10, warranting test of publication bias in these models. In this case we used the regression asymmetry test by Egger et al.,23 as well as the diagnosis by Begg et al., (nonparametric σ correlation coefficient).24 For both tests, we used the web-based software, WINPEPI (PEPI for Windows).25Ammendola et al.,PTPN22 (C1858T) polymorphism with endometriosis. Eight studies from two articles16 had Italian subjects (132 cases/528 controls), while one study had Brazilian subjects15 and another had Polish participants,14 with 140 cases/180 controls and 171 cases/310 controls, respectively.The epidemiological and clinical characteristics of the included articles are outlined in 13 had controls whose frequencies deviated from the HWE, leaving nine studies from three articles13 in HWE .Control frequencies of the variant allele in the Italian studies ranged from 0.02 to 0.06, while Brazilian and Polish populations were 0.09 and 0.12, respectively. One study12 and Polish14 populations. The significant Italian effects increased up to OR: 11.12 in the homozygous model, accompanied by wide confidence intervals (95%CI: 2.44-50.71) (13 with their study-specific OR of 122.69 and 95%CI: 13.36-1126.84.4-50.71) . Figuresheterogeneity<0.00001, I2=76-88%), less in the homozygous and recessive models .In contrast to the Italian pooled effects, the study-specific ORs were modulated in the Brazilian (OR: 1.95-2.35) and Polish (OR: 1.08-1.84) populations. Sensitivity treatment did not materially alter the overall and HWE results as the Italian findings did, thus indicating robustness of the summary effects (data not shown). All 12 pooled ORs were heterogeneous, high in the dominant and co-dominant models (PPTPN22 (C1858T) polymorphism, our meta-analysis showed overall increased risk associations of up to 5.6-fold in endometriosis, significant in all genetic models. The HWE analysis did not materially alter the overall findings, other than exacerbate susceptibility up to 9.5-fold in the homozygous model. Interpreting such an increase should, however, be treated with caution given the unusually wide CI that accompanied the pooled effects. Wide CI margins tend to heighten uncertainty, hence, less confidence in the interpretation of results.With a sample of over 1,624 for the 12 was up to 2.4-fold, and a comparably modest 1.8-fold in the Polish population.14Because there was only one of each Brazilian and Polish studies and several Italian studies, we compared these single-ethnic populations with the pooled Italian effects. By and large, the Italian effects were significant up to 11-fold in the homozygous model with the widest CIs in the entire body of results and heterogeneous. By comparison, increased risk effects in the Brazilian population14 were matched to cases compared to none in the Italian subjects. Thus, it may be one or a combination of genetic  and/or epidemiological (matching of subjects) features that rendered differences in summary effects among the three populations.These differences among the three populations may be associated with the following factors: (i) the minor allele frequencies between these three populations differed , (ii) controls in Polish studyPTPN22 and risk of endometriosis suggest this polymorphism might be a useful susceptibility marker for this disease.However, the following features of the studies account for the advantages of the non-Italian subgroup: (i) the homozygous and recessive effects in this population were obtained in zero heterogeneity; (ii) although composed of only two studies , their combined sample sizes (n=801) accounts for more than one-third (37.2%) of the total 2,152; (iii) findings in this population had the narrowest CIs, boosting precision of the findings. Given these features of the non-Italian studies, it may be that these values may be closer to the true values of association. More studies are needed to confirm our findings. Nevertheless, the observed associations between PTPN22 gene encodes the human lymphoid tyrosine phosphatase, an enzyme with restricted expression in hematopoietic cells. Lymphoid tyrosine phosphatase is a critical regulator of signaling through the T-cell receptor, and in T-cells, it forms a complex with the kinase Csk.8 The autoimmune-associated PTPN22 C1858T variant does not bind kinases well, and appears to encode a gain-of-function enzyme.26 The mechanism of action of PTPN22 in autoimmunity remains unclear. However, increased inhibition of T-cell receptor signaling caused by the PTPN22 C1858T polymorphism could predispose towards autoimmunity, either by affecting thymic deletion of autoreactive T-cells or by affecting development or function of peripheral regulatory T-cells.27 Indeed, recently, PTPN22 was found to be among the gene targets of FoxP3 in CD4+CD25+ regulatory T-cells.28The PTPN22 polymorphism may cooperate with clinical and genetic factors to influence the course of disease and immune reactions. These cooperative interactions could result in a statistical association between PTPN22 and endometriosis. Further investigations are needed to clarify the possible role of PTPN22 and other polymorphic systems in the clinical course of endometriosis. In subjects with endometriosis, PTPN22 may contribute to the development of autoimmune phenomena in the presence of peculiar circumstances.13 Given the multifactorial nature of endometriosis, the analysis of genetic factors would be proper when considering the synergy with environmental influence along with epistatic interactions.16In the presence of endometriosis, the 13 from the HWE, which may have biased summary outputs and pointed to methodological weaknesses, such as biased selection of subjects, genotyping errors, and population stratification.29 However, omitting this study followed by reanalysis did not materially alter significance and direction of association, underpinning the stability of our overall findings; (iii) the homozygous and recessive effects were characterized by unusually wide CIs in the overall analysis, which got even wider in the modifier and subgroup analyses and translate to reduced precision of the pooled ORs eliciting less confidence in the findings; (iv) there was no mention of matching in all but one14 of the component articles.Limitations of our study include the following: (i) predominant heterogeneity of the body of results indicating variance of the component studies, which may have been offset by our adjustment for this variance with use of the random-effects model; (ii) deviation of one study13 anonymous healthy adults,14 and healthy blood donors.16 Only one study15had as Control Group fertile and non-menopausal women, who had undergone tubal ligation for family planning reasons, and had no sign of endometriosis in their clinical history. The absence of symptoms in women does not exclude endometriosis, given that 16% of patients with endometriosis are fertile and asymptomatic.30Additionally, a possible limitation could be the heterogeneity of the Control Group (v), as healthy men and women,Yet, despite these limitations, the following strengths boost confidence in our findings: (i) all studies were population-based, easing extrapolation of results to the general population; (ii) all tissue sources were blood; (iii) endometriosis diagnoses were all made by laparoscopic intervention and histopathological confirmation; (iv) all studies used a combination of polymerase chain reaction (PCR) and RFLP with enzyme restriction. These five items add to the epidemiological and clinical homogeneity of the studies: consistency of increased risk effects in the entire body of results; sensitivity analysis demonstrated that the entire body of results was robust, supporting the reliability of the findings; and no publication bias was detected, indicating that the dominant and co-dominant body of results may be unbiased.The findings we report here highlight the utility of modifier analyses which provide a more comprehensive profile of an association of a polymorphism with the disease (endometriosis). Such meta-analytical treatments tend to uncover new insights into factors that retain or alter the stability or robustness of a pooled odds ratio. The synthetic approach to the individual profiles of each included study could be used to form biologically plausible subgroups.locus will be small because gene-gene as well as gene-environment interactions are likely to operate. Additional well-designed studies, based on sample sizes commensurate with detection of small genotypic risks, should allow conclusions that are more definitive as to the association of PTPN22 (C1858T) polymorphism with endometriosis.It is conceivable that endometriosis related to any


At 300 K and 5 GPa Xe(N2)2-I is synthesised, and if further compressed, undergoes a transition to a tetragonal Xe(N2)2-II phase at 14 GPa; this phase appears to be unexpectedly stable at least up to 180 GPa even after heating to above 2000 K. Raman spectroscopy measurements indicate a distinct weakening of the intramolecular bond of the nitrogen molecule above 60 GPa, while transmission measurements in the visible and mid-infrared regime suggest the metallisation of the compound at ~100 GPa.Molecular nitrogen exhibits one of the strongest known interatomic bonds, while xenon possesses a closed-shell electronic structure: a direct consequence of which renders both chemically unreactive. Through a series of optical spectroscopy and x-ray diffraction experiments, we demonstrate the formation of a novel van der Waals compound formed from binary Xe-N Under high compression, molecular nitrogen exhibits a rich polymorphism1234562 and Xe would seem unlikely due to the relative inertness of both materials. Nevertheless, a recent theoretical study predicts the formation of novel xenon nitride compounds above 146 GPa with stoichiometry - XeN62 have been explored experimentally at low pressures investigating mutual solubility25The direct reaction of N2, the metallisation pressure is drastically reduced2 compound. Here, we report the synthesis and characterisation of a Xe-N2 van der Waals compound through x-ray diffraction, Raman and transmission spectroscopies. We show that two inert condensed gases form a Xe(N2)2 compound at pressures as low as 5 GPa at room temperature. When the novel compound is formed in a xenon medium, it becomes metallic at around 100 GPa, whilst Xe(N2)2 with an abundance of nitrogen demonstrates metallic behaviour above ~140 GPa.It is known that at high pressures both xenon and nitrogen exhibit (semi-)conducting phases. Xenon has been shown to transform to metallic state at pressures between 130–150 GPa, giving it the lowest pressure of metallisation amongst the rare gas solids272822 at various concentration were loaded into diamond-anvil cells (DAC) using a combination of cryogenic and high-pressure gas-loading techniques (see Methods section). Compressing the mixture above 2 GPa leads to the formation of a xenon single crystal surrounded by liquid N2 as seen visually and in x-ray diffraction measurements  Å at 5.6 GPa 2, designated Xe(N2)2-I herein, which is in excellent agreement with the calculated equation-of-state data for Xe + 4N  resulting in the best fit to the data (see table in SM for more details on the structure refinement). The structure of this phase can be considered as a diamond-type host lattice of Xe atoms with four rotationally disordered N2 molecules forming a tetrahedron within each vacancy. The N-N site distance of 3.2655(1) Å implies a N…N closest-contact distance of 2.1655(1) Å.From both the structure type and unit-cell dimensions we determine the stoichiometry as Xe, we observe the complete transformation of the sample, evident through only the low-frequency vibrational mode and no evidence of excess N2 (see SM).Raman spectroscopy measurements of the formed single crystal at 2 GPa reveals the appearance of a weak vibrational mode, which is lower in frequency than the fluid N2 mode at 5 GPa, which consists of overlapping modes of Xe(N2)2-I, as determined by x-ray diffraction, and pure N2 that increasingly separate in frequency space at higher pressure. The vibrational mode of Xe(N2)2-I (blue spectra in 2 in Xe (red spectra in 2)2-I that form within a Xe matrix. It should be noted that the prescence of this N-containing dopant does not significantly affect the measured unit-cell volume which agrees with the literature to within experimental errorIn Raman measurements of the surrounding media (see blue spectra in 2)2-I to a high-pressure Xe(N2)2-II phase. This transition pressure corresponds approximately to the critical pressure of the δ to 2. Xe(N2)2-II adopts a body-centered tetragonal cell with a = 5.7228(3), c = 9.2134(10) Å at 18.7 GPa , 0.179(1)). This position lies displaced by 0.52(2) Å from an inversion centre resulting in four ordered N2 molecules aligned along the c-axis. Final Rietveld agreement factors are Rp = 0.015 and R = 0.094.Above pressures of 14 GPa, we observe a phase transition from the low-pressure Xe with a spherically-disordered N2 molecule model. Shortest N…N interatomic distances are now 2.5238(1) Å and 2.610(12) Å at 18.7 GPa. Recalling that the shortest N…N interatomic distances at 5.6 GPa were 2.1655 (1) Å in phase I, the alignment of N2 molecules relieves unfavourable close N…N contacts while maintaing the same coordination number for each N2 molecule.The origin of this transition lies in the ordered orientation of Nc accompanied by a reduction of −0.519(1) Å (−8.1%) along tetragonal a, corresponding to 〈110〉 in phase I (see table in SM for more details on the structure refinement). We tracked unit-cell dimensions for Xe(N2)2-II up to 58 GPa (2)2 phases (see methods section). At pressures of 38 GPa and above there were clear signs of the incipient high-pressure hcp phase of Xe accompanied by strong diffuse scattering and increased background at d-spacings overlapping with a significant number of Xe(N2)2 reflections and above 58 GPa unit-cell dimensions could not be reliably extracted from the data. However the low-angle (101) reflection could be observed up to 103 GPa  Å (+3.6%) along o 58 GPa , confirmo 58 GPa  and allo GPa see .2)2 deviates greatly from that of pure N2 2 are 2161 cm−1 and 2212 cm−1, considerably lower frequencies than either those of κ-N2 (2376 cm−1) or λ-N2 . Interestingly, at 178 GPa, we observe the persistence of molecular nitrogen, which is above the pressure at which pure N2 is claimed to become non-molecular (η-N2)122 molecular mode than that just before ζ transforms to the non-molecular amorphous η phase in pure N2, there is no evidence that the N2 molecules in Xe(N2)2 dissociate to form Xe-N bonding. However, there is a clear reduction in intensity , appear to exhibit metallic behaviour evident by the sharp rise in the absorption in the near-IR, which shifts with pressure. By 120 GPa, no detectable transmission was observed in the visible, the sample appearance became shiny and reflected red laser light (see photomicrographs in 2)2 with higher N2 concentrations do exhibit absorption 2, we are able to tune the conductive properties of Xe and lower the pressure of metallisation.sorption  green buOur results demonstrate that xenon can form compounds not only with chemically reactive gases such as hydrogen or oxygen, but also with unreactive nitrogen. That such a compound forms at low pressure, exhibits metallic properties, and stable to both high-pressure and high-temperature conditions will no doubt stimulate further research in the reactivity of xenon, an element which now appears to be substantially less inert than previously thought.μm culet flat diamonds were used for experiments under 50 GPa, while 60 μm and 150 μm culets were used for higher pressure experiments. In all experiments rhenium foil was used as the gasket material.We have studied the formation conditions and stability of xenon and nitrogen compounds up to pressures of 180 GPa in a diamond anvil cell (DAC). In total 12 DAC loadings were performed. 200 2 consisted of two stages. Solid Xe (99.9% purity) was initially cryogenically loaded into a DAC under a N2 atmosphere. Loading was confirmed initially through comparisons of white light transmission spectra due to the change in refractive index between the empty sample chamber and loaded sample. Thorough mapping of the sample with Raman spectroscopy was carried out to ensure no impurities were present in the sample and further confirmation was obtained through x-ray diffraction analysis.The loading of the Xe-N2 gas (99.9% purity) was then loaded into the cell at a pressure of 20 MPa using a high-pressure gas loading system, displacing some of the pre-existing Xe gas. The volume ratio was estimated by the phase separation of Xe and N2 in the fluid state. Using a combination of varying pressure and temperature, single crystals of the Xe rich mixture were grown.NWe have used 514 and 647 nm as excitation wavelengths in the Raman spectroscopy measurements using a custom-built micro-focussed Raman system. Pressure was determined through both ruby fluorescence (P < 100 GPa) and the Raman edge of the stressed diamondvs. 2θ plots were obtained by integrating image plate data in various formats using DIOPTAS2)2-I: V0 = 873(90) Å3, K0 = 47(56) GPa, K′ = 1(5). Equation-of-state parameters for Xe(N2)2-II: V0 = 526(158) Å3, K0 = 9(14) GPa, K′ = 4.5(11), K″ = −0.51131 GPa−1.Powder x-ray diffraction data were collected at several beamlines: BL10XU at SPring-8 (Japan), IDB PETRA-III (Germany), ID09 at the European Synchrotron Radiation Facility (France), and ID-BMD of HPCAT at APS (USA). Incident beam energies in the range 25–30 keV were used. Intensity How to cite this article: Howie, R. T. et al. Formation of xenon-nitrogen compounds at high pressure. Sci. Rep.6, 34896; doi: 10.1038/srep34896 (2016).


Acute renal failure (ARF) developed due to various causes and may lead to significant morbidity and mortality among pediatric patients.The study was conducted to determine the incidence, etiology, outcome of treatment and clinical presentation of ARF in pediatric patients in Somalia.Comprehensive case history of 39 pediatric patients below 12 years of age, admitted with renal diseases in four tertiary care hospitals in Hargeisa and Borama cities in Somalia during December 2015 to November 2016. They were subjected to clinical investigation and laboratory test analysis based on the inclusion criteria of renal insufficiency characterized by serum creatinine level more than 1.5 mg/dl.ARF was most commonly found in five to 12 years age group (53.8%) compared to infant (zero to one year) and pre-school (one to five years) children (23.08%). Mean age of presentation was 6.14 years. Male female ratio in this study was 1.2: 1. Most common presenting clinical feature in our study was oliguria (97.43%), swelling (69.2%), fever (84.1%), abdomen pain and nausea-vomiting (41.02%). Common clinical signs were edema (66.66%), altered sensorium (51.28%), hematuria (48.71%) and hypertension (38.46%). Snake bite and acute post streptococcal glomerulonephritis were the two most common causes of ARF in children in our study. Common complications were hypertension (38.46%), anemia (35.89%), hyperkalemia (25.64%) and infection (20.51%), all of which were within the previously reported range. The factors which correlated positively with increased mortality and morbidity were females with age below one year , etiology like septicemia and systemic lupus erythematosus (SLE), high peak serum creatinine concentration and complicated by disseminated intravascular coagulation (DIC).Many causes of ARF are preventable and it should be possible to reduce mortality and morbidity due to ARF through purposive preventive measure and availability of the better medical facility. Acute renal problems constitute a large proportion of hospital admission and outpatient attendance among pediatric population. Acute renal failure (ARF) in children, compared with adults, are often reported with speedy recovery without any residual effect and complications. Among the hospitalized patients, ARF may often lead to life-threatening conditions and it is regarded as one of the major cause of significant morbidity and mortality among pediatric patients. Five to 10% of patients in pediatric intensive care unit (PICU) have evidence of renal insult and ARF occurs in 8% of neonates in the neonatal intensive care unit (NICU) .Despite the major advance in the PICU tools and renal replacement therapy (RRT) methods, the reported mortality rate among inpatients ARF is 29% to 46% -4. The hThe ARF is an abrupt cessation of kidney function with life-threatening consequences  in assocAccording to AKIN, the following criteria of an abrupt within 48 hours) reduction in kidney functions are characterized by i) absolute increase in serum creatinine more than or equal to 0.3 mg/dl from baseline or ii) increase in serum creatinine more than or equal to 50% (1.5 fold from baseline) or iii) reduction in urine output (documented oliguria of less than 0.5 ml/kg / hour for more than six hours). But, in most of the cases, the baseline creatinine is not available. ARF may be non-oliguric or even polyuric in 10% to 15% of cases, which may lead to misdiagnosis on clinical assessment if we rely on daily urine volume only [ hours reThe children aged 12 years or less, suffering from ARF symptoms were enrolled between December 2015 and November 2016 in pediatric medicine department of four tertiary care hospitals in Hargeisa and Borama cities in Somalia: Hargeisa Group Hospital and Garger Hospital in Hargeisa and Al-Hayat Hospital in Borama, and Emirates Hospital in Hargeisa. The subjects were included in this study based on the inclusion criteria of renal insufficiency characterized by serum creatinine level more than 1.5 mg/dl and were excluded showing the history of any previously reported renal disease. Distinct parameters were characterized such as parameters of incidence, etiology, presentation, complications and clinical outcome. The data collected from these cases were then analyzed. All ARF patients in this study were examined clinically along with proper and complete history recording and subjected to laboratory investigations like serum levels of urea, creatinine, sodium, potassium, cholesterol, triglycerides and with complete blood count, routine and microscopic urinary examination. Other special investigations like ultrasonography (USG), antinuclear antibody (ANA), anti-double-stranded deoxyribonucleic acid (anti- dsDNA), anti-streptolysin O titer (ASO), complement component 3 (C3) level and kidney biopsy were performed whenever necessary. A prospective observational study was undertaken to evaluate the percentage of incidence of ARF among children hospitalized for all causes, the differential etiology of ARF, commonly presented clinical features, age, and sex ratio among children with ARF, and also to delineate the clinical complications and prognosis of treatment and management of cases.In the studied period, a total of 1520 children were admitted in pediatric medicine ward for the different illness and 39 cases were confirmed as ARF. Therefore, the incidence of ARF among hospitalized children in our hospitals was 2.6%. The most common cause of ARF in children in our study was snakebite  followed by post-streptococcal glomerulonephritis . Three cases were due to pneumonia and two cases each were due to gastroenteritis, sepsis, systemic lupus erythematosus (SLE), pyelonephritis and posterior urethral valve (PUV). Other cases were due to falciparum malaria, nephrocalcinosis, rapidly progressive glomerulonephritis, non-Hodgkin lymphoma, neuroblastoma, hemolytic uremic syndrome, pyogenic meningitis, atypical minimal change nephrotic syndrome and tubulointerstitial nephritis  were admitted in zero to one year age group (age up to one year included). Similarly, nine cases (23.08%) were admitted in one to five years age group and 21 cases (53.84%) were admitted to five to 12 years age group (Table 3.08% werTwenty-one cases 53.85%) were male and 18 cases (46.15%) were female children in our study with a male to female ratio of 1.2: 1. Most common cause of the ARF in the male patient was post-streptococcal glomerulonephritis  followed by snakebite , posterior urethral valve  and one case each were due to ten others different etiologies  followed by acute post-streptococcal glomerulonephritis , systemic lupus erythematosus , pneumonia  and one case each were due to six other etiologies Table . No caseThe mean age of male patients was 6.12 years and for the female patient was 6.15 years. Therefore, in male and female cases, mean age was almost the same. The mean age of each etiological group is given in Table In this study, the most common presenting symptom was oliguria . Oliguria was present in all cases except one, which was the non-oliguric renal failure due to tubulointerstitial nephritis. Other common presenting symptoms were swelling , fever , abdomen pain , nausea or vomiting . Common presenting clinical signs were edema , altered sensorium , hematuria , hypertension , hepato-splenomegaly  and others. Different presentation of ARF is given in Table Mean duration of oliguria was less than 10 days in most etiological cases. Mean oliguria for more than 10 days was present in three etiological groups. A typical minimal change nephrotic patients had oliguria for 17 days. Mean oliguria of two SLE patients was 18 days. The non-Hodgkin lymphoma (NHL) child had oliguria for one month Table -Figure 5The most common complications among all during the course of acute illness from ARF in the children was hypertension . Other complications reported were anemia , hyperkalemia , pneumonia , seizure , disseminated intravascular coagulation (DIC) (7.14%), meningitis , arrhythmia  and pleural effusion (3.57%). Eleven cases were reported without any complications . Among the 14 cases that developed anemia as a complication, five patients 35.7%) completely recovered and three cases (21.4%) died. Hyperkalemia developed in 10 cases of ARF. Fifty percent of hyperkalemia patient completely recovered, three patients (30%) died and two patients (20%) partially recovered. Two patients developed disseminated intravascular coagulation (DIC) and both of them died. Of the various infective complications, six patients (75%) developed pneumonia and two patients developed meningitis (25%). Other complications in ARF patient and their outcome are given in Table % completA total 39 cases were included and follow up has been done for a short period of two weeks. Among them, 24 cases (61.53%) recovered from ARF completely, and eight cases (20.51%) recovered partially with some persistent biochemical abnormality during discharge and follow-up. Unfortunately, seven cases died during their acute stage (17.94%) of disease Figure . Out of total nine cases in snake envenomation group, seven cases (77.8%) recovered fully, one patient (11.1%) died during acute phase due to DIC and another one child (11.1%) had persistent biochemical abnormality during follow-up. Among the total eight cases of acute renal failure following PSGN, seven patients (87.5%) recovered completely. One child (12.5%) in this group however had persistent biochemical abnormality, though the child was improving until the last follow-up visit. No patient died in this group Figure . The outcome in the different age group is depicted in Figure The outcome in different sex group is given in Figure The relationship between outcome and mean peak creatinine concentration during acute illness is given in Figure Out of 24 cases in the completely recovered group, 14 cases (58.3%) had one or more complications. Among the seven patients, who died during their acute illness, six cases (85.7%) had complications and all the patients (100%) in the partially recovered group had some complications. ARF is not uncommon in a pediatric population and has significant morbidity and mortality. The emphasis on presentation remains cardinal, but early detection and appropriate treatment can also provide complete recovery in a large proportion of ARF in children, which is the major goal of ARF therapy. The incidence of ARF in NICUs reported in some previous studies ranges from 6% to 24% of newborns . AlthougIn this study, out of total 39 cases, 21 cases were males and 18 cases were females, and the male-female ratio (M: F) was 1.2:1. This male preponderance was in consistent with previous studies, where always a higher incidence in males was reported -17. ARF Most common cause of ARF in this study was snake envenomation (23.07%) followed by acute post-streptococcal glomerulonephritis (20.5%). Other causes included pneumonia (7.7%), SLE (5.1%), PUV (5.1%), acute gastroenteritis (AGE) (5.1%), hemolytic uremic syndrome HUS (2.6%) etc. In developing countries, volume depletion from diarrhea continues to be the most common cause of ARF . Few preHUS was one of the common etiologies of ARF in children in many previous studies (12% to 24%), along with acute tubular necrosis and glomerulonephritis , 20. In Snake envenomation has contributed a substantial bulk to the etiology of ARF and has been shown in other tropical countries like Asia and Africa -23. In oThe second most common etiological factor responsible for ARF in this study was acute post-streptococcal glomerulonephritis (APSGN), which contributed 20.5% and was in consistent with previous reports . In our Overall outcome in our study has been recorded in three categories as completely recovered, partially recovered  or the patient died during the acute stage of the disease. The overall mortality in our study 17.9%) was lower than many previously published reports .9% was l. AlthougMortality in infants (zero to one year age group) was higher (33.3%) than the other two groups , which was consistent with other studies . MortaliThe precise incidence of acute renal failure in the pediatric patient is difficult to define, as it largely depends on the referral patterns, proximity to pediatric renal unit and expertise within the unit. It also depends on the population studied and the geographic location of the study. A large number of pediatric patients in our country, mainly from rural areas are not adequately managed because of poverty and lack of facilities for dialysis. Many causes of ARF in our environment are preventable and it should be possible to reduce mortality and morbidity due to ARF through purposive preventive measure and availability of the better medical facility.Our study was comparatively of short duration with the small number of cases. The follow-up was done for a very short period of time. Therefore, it was very difficult to conclude an incidence, long-term mortality, morbidity and other variables from the present study. So, it is essential to conduct a large multi-centric long-term follow-up assessment of children’s clinical condition and renal function study.