Poisoning has always been pointed as one of the leading causes of human death throughout the world. Despite the best efforts made by many research institutes, the worldwide true figure on mortalities with poisoning could never be achieved due to many reasons. One of the main reasons is the unavailability of complete database from the rural and catchment areas of the world where these types of incidents are usual. People can be made aware about this problem by presenting data articles on regular basis, therefore to mark a resource document these data should be regularly up-dated. The current data report is a briefing of types and trends of chemical poisoning amongst human in southern hilly region of Himachal Pradesh (HP), India. This research database is an outcome of five year retrospective study based on assessment of records pertaining human deaths associated with poisoning occurred in southern Himachal Pradesh, and reported at State Forensic Science Laboratory (SFSL), Junga during 2010-14. Cases where ethyl alcohol was detected have been put under exclusion criterion. All the cases were reviewed and summarized in terms of yearly and monthly frequency of reports wrapping important information portraying the involvement of gender, age, locality, types of poison, and mode of death in the poisoning incidents. Review of these scientific reports showed some notable figures having a direct concern with public and legal domains to promote risk reduction and prevention of chemical poisonings. Specifications TableValue of the data•Routine monitoring of deaths due to poisoning is an essential exercise to refreshing the database from all corners of the world. So, the current data become of high value as not much literature is available on chemical poisoning in human from HP.•The data provided here is first of its kind information for readers to fully understand types and trends of poisoning prevailing in this part of the world.•The information contained in this data report is intended for general use to assist public knowledge and research as well. These data are also a source of information for the state and native poison control centres and many other institutes to conduct research and strategize to deal this type of problem.1Due to easy availability, the use of chemical poisons has remained one of the most common ways of ending human lives by any mode of death. Large numbers of people die every year due to poisoning, especially acute pesticide poisoning 2The mountainous state of Himachal Pradesh is situated in the western Himalayan region of India. It comprises an area of 55,673 square kilometres divided into 12 districts which are further grouped into three divisions namely Shimla, Kangra and Mandi. The division of Shimla controls Shimla, Kinnaur, Sirmaur and Solan districts located in the southern region of this state. This division is a habitat of ~29% of total population and same coverage of geographical area of the state. These four districts come under the jurisdiction of SFSL established in Junga town. Post-mortem samples including blood, urine, viscera, gastric lavage or vomits material of victim obtained while autopsy are sent to this laboratory for chemical analysis of poisonous substances (if present any). The present database is inference of cases reported at SFSL, Junga from 1st January, 2010 up to 31st December, 2014. Data analysis involved all kinds of chemical poisoning.Dichlorovos and Paraquat was reported in majority (~30%) of cases. Out of 18 cases of paraquat poisoning, the maximum (10) cases were reported in year 2013 from all districts. Use of aluminum phosphide or zinc phosphide was reported in 12 cases, whereas in rest of the cases only phosphine was mentioned as poisonous substance.Database revealed 1291 positive reports out of 2721 total cases submitted during study period. Data presented herein is a realistic information depicting year wise reporting of positive cases from all selected districts , gender


Avulsion fracture of the brachioradialis origin at its proximal attachment on the lateral supracondylar ridge of the distal humerus is exceedingly rare, and only two cases have been reported in the literature so far. In this article, we present a 38 years old patient who sustained a closed avulsion fracture of the lateral supracondylar ridge of left humerus at the proximal attachment of brachioradialis following a fall backwards on outstretched hand after being struck by a lorry from behind while riding on a two-wheeler (motorcycle). He was managed with above elbow plaster for four weeks followed by elbow and wrist mobilization. At final followup, the patient had painless full range elbow motion with good elbow flexion strength. The unique mechanism by which this avulasion fracture occurred is explained on the basis of the mode of injury, position of the limb and structure and function of the brachioradialis muscle. In this report, we discuss in detail the mechanism of injury of this type of avulsion fracture, the importance of proper imaging and the line of management, with brief review of the literature pertinent to this rare injury.Avulsion fracture of brachioradialis origin is an exceedingly rare entity. Thus far only two cases have been reported in the English literatureA 38 years old male patient presented to the emergency room with left elbow pain following a road traffic injury. He was travelling in a motorcycle when he was hit by a lorry from the rear and fell backward on the outstretched hand. On physical examination, there was minimal swelling around the elbow but significant tenderness with crepitus on the lateral supracondylar ridge just proximal to the lateral epicondyle. He had restriction of active terminal elbow extension by 10 degrees with near normal active elbow flexion, pronation and supination. Active flexion and extension at wrist were painful along with the painful terminal elbow extension. There was significant pain at the lateral distal humerus when active elbow flexion against resistance was performed in the mid-pronated position of the forearm. There was no distal neurovascular deficit.Antero-posterior (AP) plain radiograph of the left elbow showed a fracture of the lateral distal humerus at the proximal part of the lateral supracondylar ridge above the epicondyle . ComputeIn view of the minimally displaced fracture, the patient was managed non-operatively with a long arm plaster cast with the elbow in 90 degree flexion and wrist held in midpronated position to avoid stresses on the wrist extensors and the brachioradialis muscle. At the end of four weeks, the cast was removed, and clinical reassessment revealed mild tenderness at the fracture site with minimal pain upon active resisted elbow flexion in the semi-pronated position of the forearm. He was started on rehabilitation with gradual elbow, wrist and finger range of motion exercises and was instructed to abstain from lifting heavy objects for a period of 12 weeks. By 14 weeks, there was no local tenderness and the resisted active elbow flexion test was painless with full strength across wrist and elbow. Follow-up radiograph showed bone healing with good callus formation .3. Avulsion fracture of the brachioradialis muscle origin at the lateral distal humerus is extremely rare, and only two cases have been reported till now2.An avulsion fracture, usually seen in athletes, occurs when a small chip of bone attached to a ligament or tendon is pulled off from the main mass of the bone due to external force or forceful eccentric contraction of muscle. The common sites of humeral avulsion fractures include the fractures of lateral or medial epicondyles and fractures of greater or lesser tuberosities4. Brachioradialis along with the extensor carpi radialis longus and brevis form the dorsal mobile wad of the forearm and are innervated by the radial nerve. Given the location of its proximal and distal attachments, this muscle has a significant mechanical advantage for elbow flexion, specifically in the mid-pronated forearm5.Brachioradialis is the most superficial muscle along the radial side of the forearm and forms the lateral border of the cubital fossa. It arises from the proximal two-thirds of the lateral supracondylar ridge of the humerus and the anterior surface of the lateral intermuscular septum and inserts on the styloid process of the distal radius1 reported one case of type I open (Gustillo-Anderson) distal humerus fracture secondary to avulsion of the brachioradialis muscle origin in a man who was thrown backwards after being struck by a fireworks shell. According to them, when the victim was thrown, he attempted to prevent the fall with his arm placed backward, forearm pronated, elbow and shoulder extended which resulted in eccentric contraction of the muscle causing the avulsion fracture with a bony spike and a grade I open fracture. They managed him with debridement without any fixation followed by 48 hours of antibiotics with good bony union by six months.Guettler and Mayoet al2 reported a similar type of case in a professional lacrosse player who sustained injury following a direct check on the lateral distal humerus by a defending player’s stick. Their patient had an associated superficial radial nerve injury along with avulsion fracture of the brachioradialis origin. The patient was treated conservatively with elbow splints with complete recovery of superficial radial nerve by eight weeks.Marchant 1 as here the patient fell backward on his outstretched hand after being struck by a lorry from the rear when he was travelling on a motorcycle. Our patient while being thrown would have attempted to prevent the fall with his arm placed backward, forearm pronated, elbow and shoulder extended. This position of the upper limb led to the forceful eccentric contraction of the brachioradialis muscle which resulted in the avulsion fracture of the muscle from its origin at the lateral supracondylar ridge of the distal humerus. This is the first case reported following road traffic injury.The mechanism of injury in our case is very similar to that reported by Guettler and MayoOn imaging, we found a 3cm crescentic bony fragment avulsed from the lateral distal humerus 1.2cm above the epicondyle with anterolateral displacement. The typical location over proximal part of the lateral supracondylar ridge, crescentic shape and anterolateral displacement of the fracture fragment in our patient were consistent with the avulsion fracture of brachioradialis muscle from its origin.One of the cases reported as in our case had been treated by immobilization with splints while the other reported case which had debridement for the open wound. The rationale for treating this avulsion fractures non-operatively is that undisplaced or minimally displaced avulsion fracture of muscle usually heal with minimal sequelae unless the bony fragment is a part of joint congruency and the muscle served as an important stabilizer for the joint. Also, open surgery carries a very high risk of injury to the radial nerve in view of its close proximity to the avulsion fracture fragment apart from the implant related complications and the need for second surgery to remove the implants.Avulsion fracture of brachioradialis muscle origin is exceedingly rare. Proper history, knowledge of the exact mechanism of injury, meticulous clinical examination and appropriate imaging will help in the diagnosis of such a rare injury. Non-operative treatment with splints for four weeks followed by mobilization is adequate for good fracture healing and functional outcome.


This study presents the findings of a questionnaire-based investigation of knowledge about the relationship of physical activity to health among adolescent participants of a community-based physical activity intervention program in São Paulo, Brazil. Qualitative  and quantitative methods were applied to examine the participants responses to two open-ended questions concerning the health benefits of physical activity and the educational goals of the intervention. More than 75% of all participants stated that health benefits (of some type) are attained through participation in physical activity. More than 50% of participants reported that the goal of the intervention was to educate people about the importance of a healthy, active lifestyle. Adolescents understand the relationship of physical activity to health as reflected in their knowledge assessments; their lifestyle choices support these beliefs. These findings offer encouragement for the development and implementation of educationally oriented interventions aimed at providing physical activity information and programming.


While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed


Over the past 10 years, key genes involved in specification of left-right laterality pathways in the embryo have been defined. The read-out for misexpression of laterality genes is usually the direction of heart looping. The question of how dextral looping direction occurred mechanistically and how the heart tube bends remains unknown. It is becoming clear from our experiments and those of others that left-right differences in cell proliferation in the second heart field (anterior heart field) drives the dextral direction. Evidence is accumulating that the cytoskeleton is at the center of laterality, and the bending and rotational forces associated with heart looping. If laterality pathways are modulated upstream, the cytoskeleton, including nonmuscle myosin II (NMHC-II), is altered downstream within the cardiomyocytes, leading to looping abnormalities. The cytoskeleton is associated with important mechanosensing and signaling pathways in cell biology and development. The initiation of blood flow during the looping period and the inherent stresses associated with increasing volumes of blood flowing into the heart may help to potentiate the process. In recent years, the steps involved in this central and complex process of heart development that is the basis of numerous congenital heart defects are being unraveled.


In human patients with autoimmune, viral, and bacterial diseases, the generation of antibodies (Abs) to foreign antigens and/or autoantibodies to self-antigens usually occurs. Some Abs with different catalytic activities  may be induced spontaneously by primary antigens and can have characteristics of the primary antigen, including the catalytic activity of idiotypic and/or anti-idiotypic Abs. Healthy humans usually do not develop Abzs or their activities are low, often on the borderline of sensitivity of the detection methods. Detection of Abzs was shown to be the earliest indicator of development of different autoimmune diseases (ADs). At the early stages of ADs, the repertoire of Abzs is usually relatively narrow, but it greatly expands with the progress of the disease, leading to the generation of catalytically diverse Abzs with different activities and functions. Some Abzs are cytotoxic and can play an important negative role in the pathogenesis of ADs, while positive roles have been proposed for other Abzs. Abzs with some low activities can temporarily be present in the blood of patients in the course of viral and bacterial diseases, but their activity increases significantly if these infections stimulate development of ADs. A significant increase in the relative Abz activities associated with a specific reorganization of the immune system, including changes in the differentiation and proliferation of bone marrow hematopoietic stem cells and lymphocyte proliferation in different organs. Different mechanisms of Abz production can be proposed for healthy externally immunized and for autoimmune mammals during the development of pathology.


The errors and associated corrections described in this document concerning the original manuscript were accountable to the production department handling this manuscript, and thus are no fault of the authors of this paper.During the production process Ou-Chen Wang was omitted from the list of corresponding authors in the original article . Both Xi


We report on a patient who was referred for port implantation with a two-chamber pacemaker aggregate on the right and total occlusion of the central veins on the left side. Venous access for port implantation was performed via left side puncture of the horizontal segment of the anterior jugular vein system (AJVS) and insertion of the port catheter using a crossover technique from the left to the right venous system via the jugular venous arch (JVA). The clinical significance of the AJVS and the JVA for central venous access and port implantation is emphasised and the corresponding literature is reviewed. Venous access for chest port implantation may be compromised for a variety of reasons and finding a suitable alternative can be difficult. If a conventional approach for this purpose is not an option, collateral veins may offer an attractive alternative. A crossover route utilising the anterior jugular venous system (AJVS) and the jugular venous arch (JVA) may be considered. We present, to the best of our knowledge, a unique case where anatomical constraints led us to utilise this crossover technique for port placement.The placement of a chest collateral port in crossover technique through the anterior jugular vein system can be quite simple and the most appropriate method in the mentioned or a comparable scenario.A 70-year-old woman was admitted to our hospital for staging and therapy of a recently diagnosed adenocarcinoma of the esophagogastric junction. The significant past medical history of the patient included implantation of a two-chamber pacemaker on the right side and subtotal sternum resection with a pectoral muscular flap graft coverage for treatment of sternum osteomyelitis. Contrast enhanced computed tomography (CT) of the thorax showed chronic occlusion of the left-sided central veins with the presence of a cervical collateral venous flow from the left to the right side reaching the nonoccluded right-sided central veins, specifically the confluence to the right innominate vein (IV) and, as part of the collateral circulation, a transverse connecting, in parts quite tortuous, and u-shape midline jugular vein measuring about 3 mm in diameter . StagingThe patient was presented to our radiological department for port implantation. We decided to opt for venous access on the left upper body to avoid problems with the pacemaker aggregate on the right upper body. The plan was to recanalise the left IV. If this proved unsuccessful, alternative access via puncture of a left-sided collateral vein to reach the contralateral central veins would be instigated.The procedure was performed under local anesthesia in our angiographic suite. Phlebography of the left arm demonstrated the venous anatomy of the shoulder region, as described above in the previously performed CT . After tIn our institution, both radiologists and surgeons utilise the anterior chest wall for the standard approach for port placement. As insertion of arm ports does not necessarily show always the best results , 2, we cFor patients with implantable cardiac devices, the general recommendation is to place the port on the contralateral side to avoid any damage to pacing or defibrillator leads during port placement , 4. FurtIn our patient, we considered a right-sided approach via the internal jugular vein (IJV) with tunnelling the catheter over a long distance to the other side, but we refrained from this because of the extended presternal scars after sternal osteomyelitis and subtotal sternal resection.In this clinical case, we proposed port placement at the left upper body to avoid problems with the pacemaker aggregate on the right side.Translumbar port placement had been discussed with the patient as an alternative, in the event of failed thoracic placement.A closer look at the anatomical conditions of our patient reveals that the supraclavicular punctured collateral vein segment is the horizontal lateral segment of the AJVS, as has been described and defined under functional and clinical aspects by Chasen and Charnsangavej  and SchuThe JVA is an infrequently found transverse connecting trunk extending across the midline between the two anterior jugular veins (AJV) of either side and lying in the suprasternal space between superficial and pretracheal layers of the cervical fascia. The JVA serves as a natural crossover collateral and may become prominent in cases of deep venous outflow obstruction. It is the midline part of the AJVS, typically in u-shape or v-shape configuration. Apart from textbooks of surgery in the context of, for example, thyroid surgery or tracheostomy, it is mentioned in the literature mostly in relation to malposition of central vein catheters or unintended crossover placement of central lines , 8.The AJVS is an important collateral venous network across the midline of the superoanterior aspect of the thorax and, if fully developed, is composed of three segments: the JVA as the transverse midline segment  and the The segmental anatomy of a fully developed AJVS is illustrated in the schematic drawing .Schummer et al.  stated tThe literature covering collateral vein access for port insertion is rather limited. Teichgräber et al.  reportedThe important role of the AJVS as a collateral also becomes apparent in the context presented by Yamada et al. , where aWe describe a case of placement of a port catheter by direct puncture of the horizontal lateral segment of the AJVS and crossover through the JVA that was technically possible without the use of special equipment, not necessitating greater effort or significantly higher costs than an ordinary port implantation, and feasible despite a tortuous and relatively narrow diameter JVA.In the unusual constellation of patients with central venous occlusion on one side and requiring ipsilateral port implantation, closer consideration of a potentially fully developed and enlarged AJVS is warranted, as this vessel has been proven clinically to be a major cervical crossover collateral vein.For clinicians, the AJVS can play an important role as a collateral for the insertion of port catheters, pacemaker leads, or other types of central devices.


Retinopathy of prematurity (ROP) is an ocular disorder which affects infants born before 34 weeks of gestation and/or with birth weight of less than 2000 grams. If not detected on time and appropriately managed, it can lead to irreversible blindness.The retinal blood vessels first appear between 15–18 weeks of gestation. These vessels grow outwards from the central part of the retina and extend towards the retinal periphery. The nasal part of the retina is fully vascularised by 36 weeks of gestation followed by the temporal retina which is completely vascularised between 36–40 weeks of gestation age . FollowiThe development of ROP can be divided into two phases - an initial phase of delayed growth of retinal vessels followed by a second phase of retinal vessel proliferation .At birth the lungs of an infant born preterm are immature placing him/her at a high risk of developing abnormally low level of oxygen in arterial blood.To overcome this, the newborn infant is given supplemental oxygen in NICU. Prior to 32 weeks of gestation, the retina is very immature and the retinal metabolic demand is low. This excess oxygen creates retinal hyperoxia and oxygen toxicity, inhibiting the production of VEGF. This is followed by temporary stopping or stoppage of normal retinal growth, and constriction of new immature vessels. As a result, there is a reduction of blood supply to retinal tissue and shortage of oxygen needed for metabolism.With increasing age of the preterm infant the retina matures. There is an increase in metabolic demand and oxygen consumption by the retina, creating a relative decrease in oxygen level. This promotes increase in the level of vascular endothelial growth factor (VEGF), triggering the formation of new blood vessels along the inner retinal surface. A demarcation ridge develops along the retina that separates the central vascularised retina from the peripheral avascular retina .The growth of retinal blood vessels at this stage may restart normally or may progress to significant ROP as seen by an abnormal growth of retinal vessels into the vitreous and over the surface of the retina. These new vessels are weak and underdeveloped failing to fulfill the oxygen demand of retinal tissue resulting in continuous growth of abnormal vessels. There is leakage of fluid or blood from these weak blood vessels. If not treated on time this can result in scarring or traction of the retina leading to retinal detachment and blindness .


The effectiveness of immigrant integration policies has gained considerable attention across Western democracies dealing with ethnically and culturally diverse societies. However, the findings on what type of policy produces more favourable integration outcomes remain inconclusive. The conflation of normative and analytical assumptions on integration is a major challenge for causal analysis of integration policies. This article applies actor-centered institutionalism as a new framework for the analysis of immigrant integration outcomes in order to separate two different mechanisms of policy intervention. Conceptualising integration outcomes as a function of capabilities and aspirations allows separating assumptions on the policy intervention in assimilation and multiculturalism as the two main types of policy approaches. The article illustrates that assimilation is an incentive-based policy and primarily designed to increase immigrants’ aspirations, whereas multiculturalism is an opportunity-based policy and primarily designed to increase immigrants’ capabilities. Conceptualising causal mechanisms of policy intervention clarifies the link between normative concepts of immigrant integration and analytical concepts of policy effectiveness. Over the last three decades, the integration of immigrants has become a salient political issue in most European countries and policy makers implemented targeted policies to foster integration of new immigrants Givens, . IntegraOn the methodological side, this article uses ‘actor-centered institutionalism’ as its framework of analysis Scharpf,  as integThis paper is structured in the following way. In a first step, the normative challenge in the current literature on immigrant integration is reviewed and the need for the conceptualization of causal mechanisms is discussed. Then I present a new institutionalist framework that proposes to evaluate the outcomes of integration policies as a function of integration capabilities and integration aspirations. In the next section follows an application of the framework to assimilation and multiculturalism as distinct types of integration policy regimes in order to derive two different logics of policy intervention. The paper concludes by assessing the benefits and implications of the proposed framework for future research.Policies of immigrant integration share the aim of steering and guiding the integration process in a more favourable direction. Any attempt to study immigrant integration policies requires a particular conceptualization of integration including the normative assumptions that a particular policy is based on. As argued by Spencer and Charsley , any undAlthough there is no universal definition of the term, the core meaning of integration is commonly described a social process of settlement and the accommodation by both the native and the immigrant populations, resulting in an increased social membership of immigrants Givens, , p. 72. As an opposing mode of integration, the concept of multiculturalism has become an important focus of scholars and policymakers.Literature on immigrant integration has mainly focused on assimilation and multiculturalism as two opposing modes of integration  and regulatory institutions (policies).The framework presented in Table Public policies, such as immigrant integration policies, are specific institutions affecting the life of individuals much more directly than the formal design of the state that is commonly defined as institutions  immigrants to participate in the receiving country  which makes it necessary to make costly efforts to ensure they become an integrated part of society. Integration is understood to be a burdensome process that needs efforts to make up for deficiencies of immigrants. The duty lies primarily with the immigrant that is expected to undertake integration efforts. Accordingly, policies of assimilation are designed to influence the interest of immigrants in adapting to the majority population. They are characterised by a restrictive provision of rights to immigrants. The provision of equal rights and citizenship is granted only after migrants successfully integrated into society. The theoretical expectation is that this restrictive and conditional provision of rights incentivizes immigrants to undertake integration efforts. The incentives of assimilation policies are expected to drive immigrants, who would otherwise stay within their ethnic groups, to acquire the necessary linguistic and cultural skills to integration. Higher aspirations in turn are expected to contribute positively to immigrants’ capabilities: If immigrants are interested enough in integration the opportunities will follow see Fig. . Thus, aincentive-structure influencing the aspirations of immigrants, here, whether to aim for the acquisition of country-specific skills and inter-ethnic contacts, or a preference for staying within ethnic communities.As illustrative example for this approach, the influential empirical study of Koopmans 9 where tIn the second perspective of multiculturalism, immigrant integration takes place as a process of inclusion. The acquisition of country-specific skills is meant to enable immigrants to participate as equals and to unfold their potential in the receiving society. Immigrants are perceived as individuals with potentials and an intrinsic motivation to take part in the society of the receiving country. The duty lies primarily with the receiving society that is supposed to provide opportunities for the participation of immigrants on equal terms. Accordingly, policies of multiculturalism are designed to influence the ability of immigrants to integrate. They are characterised by an extensive range of rights granted to immigrants. The theoretical expectation is that a liberal provision of rights to immigrants facilitates their participation. Rights provide resources and access to institutions that increase the ability of immigrants to realise equal participation. Thus, any systematic underperformance of immigrants is expected to be the result of their limited capabilities. More capabilities are expected in turn to contribute positively to immigrants’ aspirations: If immigrants are able to participate as equals, their perception of opportunities is given a boost and instil immigrants a belief that they can thrive in the receiving society see Fig. .10 If riopportunity-structure influencing the capabilities of immigrants, whether immigrants are able to political mobilization and participation. Whether immigrants decide to participate is seen depending primarily on the resources available to them.As illustrative example for this approach is the prominent research of Irene Bloemraad on the political integration of immigrants  or employment (socio-economic) or social belonging .The essential feature of actor-centered institutionalism is that it allows for the combination agency and structure within a uniform explanatory framework. Furthermore, the new framework allows learning how different ideas about the normative nature of the integration process result in particular types of policy intervention and what causal mechanism they imply. This might not only facilitate to disentangle contradicting findings on integration policy effectiveness but may also minimize the implicit transmission of outdated and stereotypical attributions of policy regimes on the interpretation of policy outcomes. The two concepts of assimilation and multiculturalism imply different specifications of the policy problem, and identify different causal pathways behind the relationship between the policy output and the policy outcome.The comparative analysis of immigrant integration policies face opposing normative notions of integration and a lack of concept validity when it comes to empirical measurements of policies. As a result, empirical evidence on which types of integration policy contribute under which circumstances to favorable integration outcomes remains inconclusive and disputed.The argument lined out in this article is that the confusion in the literature is at least partially the result of the underspecification of causal mechanisms regarding different types of integration policies. How specific policies are assumed to intervene into the integration process remains often a blackbox. Therefore, these assumed mechanisms need to be specified in a systematic manner and the nature of integration process linked with a concept of policy intervention. By applying the perspective of actor-centered institutionalism to integration policy outcomes a new coherent framework distinguishing integration capabilities from integration aspirations is presented. In this perspective, integration can be conceptualised as a function of individual aspirations to become a full member of the receiving country, and the individual capability to translate these aspirations into effective integration. In order to participate in and feel belonging to the receiving country, immigrants require both the motivation to integrate and the ability to do so.The application of this capability-aspiration framework to the policy design of multiculturalism and the policy design of assimilation illustrates how these two opposing policy types differ in their assumption about the policy problem, the policy solution, and the logic of policy intervention. Different policy regimes for immigrant integration address different aspects of the integration process and the dynamics between the individual immigrant and the society at large: assimilation seeks to strengthen the aspiration of immigrations, whereas multiculturalism seeks to strengthen the capabilities of immigrants. The integration policy problem is either seen as under-aspiration in the case of assimilation, or as under-capability in the case of multiculturalism. Accordingly, in the perspective of assimilation, integration outcomes can be improved by fostering immigrants’ aspirations. In the perspective of multiculturalism, integration outcomes can be improved by fostering immigrants’ capabilities. The fundamentals of the proposed framework are considering capabilities and aspirations as two sides of the integration coin, and the assignment of rights to immigrants as a potential double-edged sword. The study illustrates why assimilation and multiculturalism remain the main concepts of immigrant integration: they are based on two different visions of the integration process shaping two opposing premises about the policy problem and the remedy to it. Assimilation and multiculturalism form public philosophies of integration that structure and constrain their specific policy interventions. This article argues that assimilation is an incentive-based theory and multiculturalism is an opportunity-based theory.Nevertheless, the chosen approach of actor-centered institutionalism may ignore or conceal certain aspects of integration processes. Other explanatory approaches focussing on factors such as ethnic discrimination or educational resources are complementary to the proposed framework. Considering integration outcomes as a product of capabilities and aspirations is illuminating for an institutionalist perspective on integration policy outcomes and allows identifying specific policy intervention logics as demonstrated in this article. The benefits of this study are threefold. Firstly, from a theoretical perspective, the capability-aspiration framework provides a conceptual tool for the analysis of the effectiveness of policy interventions by combining the idea of an agency-structure relationship of actor-centered institutionalism with the comparative study of immigrant integration. Instead of a full-fledged explanation model, the capability-aspiration framework is a research heuristic on a high level of abstraction that allows the identifying and arranging of different explanatory factors relevant for immigrant integration outcomes in different dimensions.how policies are expected to influence integration outcomes of immigrants. The framework may help to translate normative notions of integration into useful analytical concepts of policy intervention to identify complex causal relationships.Secondly, from an empirical perspective, I illustrate how the contradicting findings in the literature can be disentangled, and elaborate on differences in the policy problem, the policy solution, and distinct causal mechanisms that have only been assumed implicitly in existing studies. While there are useful normative and descriptive typologies of integration policy regimes, the capability-aspiration framework offers a mechanistic typology of Thirdly, from a practical perspective, the new framework can help to understand the motivation and reasoning of politicians regarding specific integration policy interventions. Gaining certainty about the (perception of the) policy problem will allow policy-makers to draft more targeted policy intervention by anticipating the effects on immigrants’ capabilities and aspirations. The framework allows establishing clear links between the notion of integration and the corresponding policy intervention. Therefore, the proposed heuristic may provide a useful tool, sharpening the understanding of integration policy effectiveness.Once established that integration outcomes are a complex interaction of aspirations and capabilities and that integration policy effectiveness depends on a complex interaction of incentives and opportunities, we can start building up systematic knowledge of how they interact. If this conceptual distinction is ignored or incentives and opportunities are taken as the same thing, we risk to reproduce the normativity trap and to miss the complex interaction of aspirations and capabilities. Future research should further specify and investigate the causal mechanisms outlined in this study in order to solve the puzzle of contradicting findings in existing literature on immigrant integration. Empirical studies on policy effectiveness may gain explanatory power if they specify capabilities and aspirations as mediating factors. The major challenge for future research will be to find empirical strategies to measure capabilities and aspirations in specific dimensions of immigrant integration in order to test the different logics of policy intervention against each other. The capability-aspiration framework provides a research heuristic meant to facilitate comparative studies over mutually exclusive approaches to immigrant integration, and proposes to focus on assumed but broadly untested causal relationships in different types of integration policy regimes.


Anatomical variations of the celiac trunk and its branches are particularly important from a surgical perspective due to their relationships with surrounding structures. We report here a particularly rare variant involving absence of the celiac trunk in association with trifurcation of the common hepatic artery. These variations were found in an adult male cadaver. We perform a review of the literature and discuss the clinical and embryological significance of these variations. Recognition of celiac trunk and hepatic artery variations is of utmost importance to surgeons and radiologists because multiple variations can lead to undue complications. The celiac trunk (CT) or celiac artery is the first ventral splanchnic branch of the abdominal aorta. It is the artery of the foregut and it originates from the ventral aspect of the abdominal aorta at the level of the junction between the T12 and L1 vertebrae. It is about 1.5-2 cm in length and usually terminates by dividing into three main branches: the left gastric, common hepatic and splenic arteries.During dissection classes for medical undergraduates, we observed the following variations of abdominal blood vessels in an adult male cadaver aged approximately 60-65 years, with a height of approximately 1.65 m, and body weight of 60 kg. The celiac trunk was absent. The left gastric artery, splenic artery and common hepatic artery all arose directly from the abdominal aorta . The supAnatomic variations of the celiac trunk and its branches are the result of anomalous embryogenesis of primitive ventral blood vessels originating from the abdominal aorta. Each dorsal aorta gives off ventral splanchnic arteries which supply the gut and its derivatives. Initially, these ventral branches are paired, but with the fusion of the dorsal aorta, they also fuse to form a series of unpaired segmental arteries which run in the dorsal mesentery of the gut. They gradually fuse to form the arteries of the foregut, midgut, and hindgut.Absence of the celiac trunk is a rare anomaly with incidence rates ranging from 0.1Knowledge of anatomical variations of the celiac trunk is important for surgeons during liver transplantation, laparoscopic surgery, radiological abdominal interventions, and penetrating injuries to the abdomen. Also, acquaintance of unique variations of absence of the celiac trunk may be useful in planning and performing radiological interventions such as celiacographyAnother variation that we report here is trifurcation of the common hepatic artery. Although many reports have been published on variant branches of the hepatic artery, its trifurcation is uncommon. Nayak et al.Recent advances in imaging studies have made accurate evaluation of the vascular anatomy of the upper gastrointestinal tract easier. Recognition of celiac trunk and hepatic artery variants is of utmost importance because it aids in planning of several surgical and interventional procedures, thereby helping to avoid undue complications.


Here, I discuss recent advances and the molecular details of the DNA segregation machinery, focusing on the formation of the segrosome complex.Bacterial extrachromosomal DNAs often contribute to virulence in pathogenic organisms or facilitate adaptation to particular environments. The transmission of genetic information from one generation to the next requires sufficient partitioning of DNA molecules to ensure that at least one copy reaches each side of the division plane and is inherited by the daughter cells. Segregation of the bacterial chromosome occurs during or after replication and probably involves a strategy in which several protein complexes participate to modify the folding pattern and distribution first of the origin domain and then of the rest of the chromosome. Low-copy number plasmids rely on specialized partitioning systems, which in some cases use a mechanism that show striking similarity to eukaryotic DNA segregation. Overall, there have been multiple systems implicated in the dynamic transport of DNA cargo to a new cellular position during the cell cycle but most seem to share a common initial DNA partitioning step, involving the formation of a nucleoprotein complex called the segrosome. The particular features and complex topologies of individual segrosomes depend on both the nature of the DNA binding protein involved and on the recognized centromeric DNA sequence, both of which vary across systems. The combination of  The process of DNA segregation is a crucial stage of the bacterial cell cycle and it depends on the precise coordination with other cellular events. The faithful inheritance of genetic information during cell division ensures that each daughter cell receives a copy of the newly replicated DNA. In many organisms, the DNA-encoded genome consists of a core genome (the chromosome) and accessory genomes . MGEs  often confer evolutionary advantages to the host bacteria, including the adaptation to different environmental niches. Many, if not most, naturally occurring MGEs are in low or unique copy number and thus bring their own post-replication survival apparatus encoded in stability determinants .par) systems help to reliably segregate sister DNAs via a process that could be seen as functionally analogous to the mitotic segregation of chromosomes in eukaryotic cells. The best studied and probably the most common partitioning systems constitute a compact genetic module that is tightly auto-regulated by one of the gene products and consists of only three elements: a cis-acting DNA sequence and two trans-acting proteins. The DNA sequence denotes a par site or centromere-like region, and can be located at a single site (upstream or downstream of the operon) or at multiple positions within the MGE. The trans-acting proteins consist of a centromere-binding protein (CBP) that binds to the centromere and forms a nucleoprotein complex (partition complex or segrosome), and a motor protein (an NTPase), that sometimes is a cytomotive filament, which effectively moves the MGE inside the bacteria through direct interaction with the segrosome. Initially, these systems were classified as follows, based on the molecular nature of the NTPase: type I , which further divided into Ia and Ib based on differences in the trans-acting proteins and the position of the centromere in the operon; and type II   vary, the sites always contain inverted repeats. The parS site contains two different repeats asymmetrically arranged around a binding site for the IHF protein  or the DNA wraps around a CBP oligomer (type II and III partition systems). The resulting segrosome is a single and discrete structure.par operon and consists of direct and inverted repeats. However, in plasmid pCXC100 the centromeric site contains only direct repeats  is continuous and consists of direct and inverted repeats separated by AT-rich regions. A DNA region between the operon genes and the centromere (OF) comprises more repeats that play important roles in partitioning and transcription regulation  consists of tandem repeats localized in a single locus upstream of the operon. The arrangement can be continuous  is localized upstream of the operon and contains several direct repeats in a single locus that can be split into two (pBtoxis) or three (pBsph) blocks, resembling discontinuous parC sites , located downstream of the partition operon (Oliva et al., It is still common for new partitioning systems to be discovered in plasmids, phages, and on chromosomes. Together with a growing body of molecular insights these will help to broaden our understanding of DNA trafficking during bacterial cell division and in particular how DNA is attached to the CBP during segrosome formation and then to the motor protein through the segrosome.MO conceived and wrote this mini-review.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling Editor declared a shared affiliation, though no other collaboration, with the author and states that the process nevertheless met the standards of a fair and objective review.


Pruritus can be one of the important factors of exacerbation of discomfort in patients with chronic renal failure. In an unpublished clinical trial which was performed in the Semnan University of Medical Sciences, the effect of reduction of dialysate temperature on controlling the pruritus was assessed. The results suggest a positive effect. The author recommends further studies to consider reducing dialysate temperature on control of pruritus.Pruritus is a common problem in patients with chronic renal failure 25 to 35% before dialysis patients and 60 to 80% of dialysis patients may complain of pruritus . DespiteThe use of opioid antagonists in treatment of uremic pruritus have been based on this matter that endogenous opioid peptides accumulate in uremic patients and its concentration increases in plasma. In a controlled study the effects of naltrexone on pruritus in hemodialysis patients was studied and showed a positive effect in these patients, although another study showed controversy result . In a stThere is an important matter which is in addition to other problems; pruritus can be one of the important factors of exacerbation of discomfort in patients with chronic renal failure. In an unpublished clinical trial that was performed in the Semnan University of Medical Sciences, the effect of reduction of dialysate temperature on controlling the pruritus was assessed. The results suggest a positive effect . Some syConclusionPruritus can be one of the important factors of exacerbation of discomfort in patients with chronic renal failure. In an unpublished clinical trial which was performed in the Semnan University of Medical Sciences, the effect of reduction of dialysate temperature on controlling the pruritus was assessed. The results suggest a positive effect. The author recommends further studies to consider reducing dialysate temperature on control of pruritus.MRT was the single author of the paper.The author declared no competing interests.Ethical issues  have been completely observed by the author.None.


Streptococcus pneumoniae (pneumococcus) is the leading infectious cause of childhood bacterial pneumonia. The diagnosis of childhood pneumonia remains a critical epidemiological task for monitoring vaccine and treatment program effectiveness. The chest radiograph remains the most readily available and common imaging modality to assess childhood pneumonia. In 1997, the World Health Organization Radiology Working Group was established to provide a consensus method for the standardized definition for the interpretation of pediatric frontal chest radiographs, for use in bacterial vaccine efficacy trials in children. The definition was not designed for use in individual patient clinical management because of its emphasis on specificity at the expense of sensitivity. These definitions and endpoint conclusions were published in 2001 and an analysis of observer variation for these conclusions using a reference library of chest radiographs was published in 2005. In response to the technical needs identified through subsequent meetings, the World Health Organization Chest Radiography in Epidemiological Studies (CRES) project was initiated and is designed to be a continuation of the World Health Organization Radiology Working Group. The aims of the World Health Organization CRES project are to clarify the definitions used in the World Health Organization defined standardized interpretation of pediatric chest radiographs in bacterial vaccine impact and pneumonia epidemiological studies, reinforce the focus on reproducible chest radiograph readings, provide training and support with World Health Organization defined standardized interpretation of chest radiographs and develop guidelines and tools for investigators and site staff to assist in obtaining high-quality chest radiographs.Childhood pneumonia is among the leading infectious causes of mortality in children younger than 5 years of age globally.  Streptococcus pneumoniae (pneumococcus) is the leading infectious cause of childhood bacterial pneumonia; it is estimated to have caused 411,000 and 335,000 deaths globally in 2010 and 2015, respectively, in children in this age group [Streptococcus pneumoniae and Haemophilus influenzae type b, has become routine in low-income countries with the widespread introduction of pneumococcal conjugate vaccines and the Haemophilus influenzae type b vaccine in the past decade [Childhood pneumonia is among the leading infectious causes of mortality in children younger than 5 years of age globally. . StreptoHaemophilus influenzae type b and pneumococcal conjugate vaccines vaccine trials , and for determining this spectrum of disease burden from epidemiological studies. The definitions were not designed for use in individual patient clinical management because of their emphasis on specificity at the expense of sensitivity [It is recognized that the chest radiograph has a number of limitations compared to imaging modalities like ultrasound (US) and computerized tomography (CT) of the chest in the diagnosis of childhood pneumonia –10. Howesitivity .Haemophilus influenzae type b pneumonia. If the endpoint lacks specificity, the number of false-positives increases, which reduces the power and precision of the bacterial vaccine trial. Therefore, the World Health Organization standardized chest radiograph definition of primary endpoint pneumonia, which is used as the endpoint in bacterial vaccine trials, compromises on sensitivity, recognizing that certain cases will be missed, but that this does not greatly affect the precision of the vaccine efficacy outcome. The World Health Organization standardized definition of other infiltrates is not used as an endpoint in bacterial vaccine trials [In bacterial vaccine trials, specificity for measurement of vaccine efficacy is emphasized, with the aim to establish whether the vaccine has activity to prevent pneumococcal or e trials , 15.These World Health Organization standardized definitions and endpoint conclusions were published in 2001, and an analysis of observer variation for these conclusions using a reference library of chest radiographs was published in 2005 . The refHaemophilus influenzae type b Initiative Radiology Workshop in Hanoi, Vietnam, in 2011 [By 2005, World Health Organization support for standardized chest radiograph interpretation had declined due to resource limitations, despite the increasing application of this tool in a number of epidemiological settings. The applications included pneumonia vaccine efficacy trials, pneumonia vaccine probe studies, malaria efficacy trials, an evaluation of indoor air pollution reduction, pneumonia surveillance activities and pneumonia etiology studies –19. Reco in 2011  and a se in 2011 . These m in 2011 , 15.In response to the technical needs identified through these meetings, the World Health Organization CRES project was initiated. It is designed to be a continuation of the World Health Organization Radiology Working Group. The World Health Organization CRES project is a subproject of the pneumococcal conjugate vaccines technical coordination project, which is a collaboration between the Immunization, Vaccines and Biologicals Department of the World Health Organization and the Johns Hopkins University Bloomberg School of Public Health, in Baltimore, Maryland, funded by the Bill and Melinda Gates Foundation. The World Health Organization CRES project is based at the Murdoch Children’s Research Institute in Melbourne, Australia, and is particularly important for countries with planned or ongoing studies to measure the impact of pneumococcal conjugate vaccines, especially in Asia where the uptake of pneumococcal conjugate vaccines has lagged behind that of other regions.The aims of the World Health Organization CRES project are to clarify the definitions used in the World Health Organization defined standardized interpretation of pediatric chest radiographs in vaccine impact and pneumonia epidemiological studies , reinforThe clarifications to the original World Health Organization standardized chest radiograph interpretation definitions  relate tThe silhouette sign refers to the absence of depiction of an anatomical soft-tissue border. The silhouette sign results from the juxtaposition of structures of similar radiographic attenuation and this sign actually refers to the absence of a silhouette. It is caused by consolidation and/or atelectasis of the adjacent lung, a large mass or by contiguous pleural fluid . HoweverA footnote to the original World Health Organization definitions refers to the silhouette sign as follows: “In the presence of any visible adjacent opacity, a silhouette sign, where the length of loss of an anatomical border is greater or equal to the length of a posterior rib and one adjacent rib space at the same level, is considered to indicate of endpoint consolidation. A silhouette sign of this size without a visible adjacent opacity is considered to fulfill the definition of other infiltrate.” This is illustrated in Fig. An updated set of reference training chest radiographs is being developed under the World Health Organization CRES project. Prior to the June 2016 meeting, the World Health Organization Technical Working Group applied the proposed clarifications to the World Health Organization definitions by interpreting a set of 400 chest radiographs that were not part of the original World Health Organization reference training set  and 50 chest radiographs from the original World Health Organization reference training set. These 450 chest radiographs were read by the World Health Organization Technical Working Group members and assigned to one of the three conclusions. Thirteen readers from the World Health Organization Technical Working Group completed all 450 chest radiographs at the time of a data freeze on 20 June 2016. Detailed analysis of these readings showed good correlation between the final reading using the original World Health Organization definitions and those of the new readers using the clarified criteria. As described in the literature using World Health Organization defined standardized chest radiograph definitions , the intThe new set of World Health Organization training chest radiographs are being prepared, emphasizing the need for inclusion of chest radiographs with a high World Health Organization CRES committee reader agreement. The chest radiographs will have comments and annotations added by a subgroup of the World Health Organization CRES project in order to improve their value as a teaching tool. Guidelines for the training and assessment of chest radiograph readers and support for studies in the form of a centralized arbitration process for discordant chest radiograph interpretations are also under development.The original World Health Organization Radiology Working Group provided standardized definitions on chest radiograph quality. An adequate chest radiograph allows for confident interpretation for primary endpoint pneumonia and other infiltrates. Suboptimal chest radiograph allows for the interpretation of primary endpoint pneumonia but not for other infiltrates. Uninterpretable chest radiograph is not interpretable with respect to the presence or absence of primary endpoint pneumonia or other infiltrates  Table 11. The cuThe World Health Organization CRES project aims to support investigators using the World Health Organization standardized methodology for interpreting pediatric chest radiographs for vaccine efficacy and pneumonia epidemiological studies, including providing clarifications to the original World Health Organization defined standardized chest radiograph interpretation, an updated reference training set of chest radiographs, resources for the training and assessment of readers, guidance on chest radiograph quality and safety, updated reference publications and a centralized arbitration process for the resolution of chest radiographs with discordant interpretations. The final World Health Organization materials and guidance are expected to be published and available in 2017.


Trail Registration. The case report is registered in Research Registry under the UIN researchregistry743.Minimally invasive hysterectomy is a standard procedure. Different approaches, as laparoscopically assisted vaginal hysterectomy, vaginal hysterectomy, and subtotal and total laparoscopic hysterectomy, have been described and evaluated by various investigations as safe and cost-effective methods. In particular, in comparison to abdominal hysterectomy, the minimally invasive methods have undoubted advantages for the patients. The main reason for a primary abdominal hysterectomy or conversion to abdominal hysterectomy during a minimal invasive approach is the uterine size. We describe our course of action in the retrospective analysis of five cases of total minimal-access hysterectomy, combining the laparoscopic subtotal hysterectomy and the vaginal extirpation of the cervix in uterine myomatosis with a uterine weight of more than 1000 grams, and discuss the factors that limit the use of laparoscopy in the treatment of big uteri. The disadvantages of abdominal hysterectomy in comparison to the vaginal or laparoscopic approach have been shown in various studies . HoweverRetrospective analysis of the outcome of five cases of total minimal-access hysterectomy is realized by the same gynecologic surgeon in uteri of more than 1000 grams.We realized five total laparoscopic hysterectomies with a median weight of 1422 grams (1035–2100 g.). In all five cases we performed a laparoscopic subtotal hysterectomy with electric morcellation and subsequent vaginal extirpation of the cervix. The median duration of surgery was 194 min (135 min.–237 min.). In all cases we performed an initial diagnostic hysteroscopy to avoid the morcellation of intrauterine malignant pathologies and used an abrasor as uterine manipulator and an electric power morcellator.In all five cases the premenopausal patients presented with bleeding disorders (hypermenorrhea and dysmenorrhea) and symptoms due to the uterine size such as compression of bladder and bowel and pressure on the sacral plexus . The preWe performed the supracervical resection of the uterine body after coagulation of the ascending branches of the A. uterina, avoiding contact to the bladder and the ureteral region. The morcellation was performed with a 15 mm reusable electric morcellator applicate through the left inferior incision. Subsequently the cervix was easy to resect by vaginal approach avoiding abdominal contact to the ureter, followed by peritoneal closure and suture of the vaginal cuff. The localization of the optical trocar depended on the cranial uterine extension. We choose an incision in the median line between umbilicus and xiphoid process epigastric area or an alternative first approach in the Palmers Point. In three cases we used 2 auxiliary trocars (5 mm), in two cases 3 auxiliary trocars, and in each case a 5 mm optical system . Thus thA good surgical result is always based on a correct indication. In case of very large fibroid uteri the evaluation of the possibility of a minimally invasive approach has to consider the uterine size, uterine mobility, the patients clinical history (prior surgeries and adhesion), and general physical conditions. The examination in general anesthesia by the experienced surgeon must be part of the presurgical evaluation. The success of the total minimal-access hysterectomy in uteri of more than 1000 grams also depends on the following factors: surgical experience of the team, instrumental equipment, positioning of the patient, uterine mobilization by a manipulator, and the flexibility of the anterior abdominal wall, the intraabdominal residual volume and ventilation pressure respectively. The duration of the surgery also depends on these factors and not only on the uterine weight. Interestingly we were able to realize the fastest surgery in the largest uterus. De Wilde showed the possible complications depending on the duration of a surgery . TherefoTchartchian et al. described the combined laparoscopic hysterectomy (LACH) in a case of a uterus with a weight of 2400 grams using the so-called switch-over technique , which mIn all cases we preferred to combine the laparoscopic subtotal hysterectomy with the subsequent vaginal extirpation of the cervix, instead of performing a total laparoscopic hysterectomy. The most important surgical step in laparoscopic hysterectomy is the devascularisation of the uterus. After the coagulation and dissection of the uterine arteries the risk of bleeding is minimal. In case of a total laparoscopic hysterectomy the preparation of the bladder and the paracervical region would be the next step. As the preparation in big uteri is more difficult than normal, the laparoscopic subtotal hysterectomy is easier to perform and can avoid bladder and ureteral complications. Cipullo et al. described a higher rate of major complications in TLH compared to LASH . MorelliA condition of the total minimal-access hysterectomy is the morcellation of the uterine body with an electric morcellator in order to extract the tissue from the abdominal cavity. Because of potential tissue dissemination within the abdominal cavity, the Food and Drug Administration recently warned against the use of electromechanical power morcellation in hysterectomy and myomectomy . The risIn large uteri of more than 1000 grams the total minimal-access hysterectomy is a safe surgical approach with all the advantages of minimally invasive surgery. The feasibility of the method does depend not only on the uterine weight but on a complex variety of factors that must be considered in the process of indication by the experienced surgeon. Thus abdominal hysterectomy can be even avoided in many cases of big uteri.


Schizophrenia spectrum disorders have major implications for the individuals, their families and society.Antipsychotic medication is the cornerstone in the treatment of psychotic symptoms and is effective in the reduction of psychotic symptoms and of relapse after remission of psychotic symptoms. This is the reason for recommending maintenance treatment with antipsychotic medication in national and international guidelines for the treatment of schizophrenia, one year after remission of psychotic symptoms in first episode psychosis.The aim of the study is to investigate the effect of tapered discontinuation versus maintenance therapy with antipsychotic medication in patients with newly diagnosed schizophrenia or persistent delusional disorder and with minimum three months remission of psychotic symptoms, and to find minimal effective dose of antipsychotic medication. Negative symptoms, cognitive impairments and the side effects of antipsychotic medication can cause a serious and long-term burden for patients and can reduce their quality of life. The TAILOR study will investigate these important aspects.The study is a randomized multicenter single blinded clinical trial. The aim is to include 250 patients from the outpatient early intervention program, OPUS, a 2 years manualized psychiatric treatment programme. At baseline patients must have 3 months remission of psychotic symptoms as documented by the SAPS (Schedule for Assessment of Positive Symptoms in Schizophrenia).The patients will be randomized to either tapered discontinuation or dose reduction of antipsychotic medication or treatment as usual stratified according to substance abuse. The intervention will last for 1 year, and follow up interviews will be made after 1,2 and 5 years.The patients will receive a user-developed mobile phone application to make daily registrations.The study has been including patients since May 2017.The first data is expected in 2019.The TAILOR trial will contribute to knowledge about the effect of tapering/discontinuation of antipsychotic medication in early phases of schizophrenia spectrum disorders and hopefully the results may guide future clinical treatment regimens of antipsychotic medication.The trial is a complex medical intervention, and it raises ethical, practical and organizational challenges.When designing the TAILOR trial ethical questions were raised regarding blinding and the design of the intervention. In the trial only the researchers are blinded, neither clinicians nor patients, because they should be attentive of the high risk of relapse in the discontinuation group. The design gives the clinicians the possibility to adjust the dose of the antipsychotic medication to ensure sufficient treatment. Therefore, the trial only includes assessor blinding and the groups might end up being more similar than intended.In general, it is of ethical consideration that the trial participants in the tapering/discontinuation group will be subjected to a higher risk of relapse. On the other hand, it seems unethical if research were not to discover the group of patients who can discontinue antipsychotic medication without relapsing.Practical challenges will be sufficient recruitment or patient motivation and dropout.


Background. The evidence exists that radicals are crucial agents necessary for the wound regeneration helping to enhance the repair process. Materials and methods. The lineshape of the electron paramagnetic resonance (EPR) spectra of the burn wounds measured with the low microwave power (2.2 mW) was numerically analyzed. The experimental spectra were fitted by the sum of two and three lines. Results. The number of the lines in the EPR spectrum corresponded to the number of different groups of radicals in the natural samples after thermal treatment. The component lines were described by Gaussian and Lorentzian functions. The spectra of the burn wounds were superposition of three lines different in shape and in linewidths. The best fitting was obtained for the sum of broad Gaussian, broad Lorentzian, and narrow Lorentzian lines. Dipolar interactions between the unpaired electrons widened the broad Gaussian and broad Lorentzian lines. Radicals with the narrow Lorentzian lines existed mainly in the tested samples. Conclusions. The spectral shape analysis may be proposed as a useful method for determining the number of different groups of radicals in the burn wounds. The healing process of burn wounds with the loss of tissue and infection of the damaged place occurs by granulation. Healing of burn wounds is a complex, biologic process, based on the replacement of the damaged tissue with a living one , 2. Restnd Il-10 . Radicalnd Il-10 . HoweverThe numerical analysis of the lineshape of the electron paramagnetic resonance (EPR) spectra was performed to find different groups of radicals in the burn wounds. Different types of thermally formed radicals in skin and tissue revealed characteristic EPR signals, which were identified. The aim of this study was the application of numerical procedures to multicomponent microwave absorption curves to obtain information about the number of different groups of radicals in the burn wounds. This work was the continuation of our earlier comparative EPR studies of different groups of radicals in the burn wounds treated with the propolis and silver sulphadiazine salt . The advThe study protocol was approved by the Regional Ethics Committee for Experiments on animals of the Medical University of Silesia. The experiments were conducted in the Central Experimental Animal Quarters of the Medical University of Silesia. The Polish Landrace pigs were kept in uniform zoohygienic conditions both before and during the experiment. The animals were fed with a balanced mixture R 233 in the full physical and mental comfort eliminating the stress reactions. The skin burn wounds were inflicted according to Hoekstra's model . In the The EPR spectra of the burn wounds located in the thin-walled glass tubes with the external diameter of 3 mm were measured at room temperature by the use of an X-band (9.3 GHz) electron paramagnetic resonance spectrometer of the Radiopan Firm  with magnetic modulation of 100 kHz. The mass of the samples in the tubes was obtained by weight of Sartorius Firm (Germany). The mass of the burn wounds samples was calculated as the difference between the mass of the tube with the sample and the mass of the empty tube. The high-paramagnetic purity characterized the tubes and they were of the EPR signals in the measurement conditions.oM is the total produced microwave power (70 mW) and M is the microwave power used during the EPR measurement. Microwave frequency (ν) was directly measured by MCM101 recorder produced by EPRAD Firm .The total microwave power produced by klystron in the microwave bridge of the EPR spectrometer was 70 mW. The EPR spectra were recorded without microwave saturation effects with the low microwave power equal to 2.2 mW. This low value of microwave power corresponded to the high value of attenuation equaling 15 dB, according to the formula (1)attenThe EPR spectra were measured as the first derivative of microwave absorption. The Rapid Scan Unit of Jagmar Firm  was used as the data acquisition system. The professional spectroscopic program of the Jagmar Firm and LabView program (USA) was applied.S).The lineshape of the EPR spectra of the burn wounds were numerically analyzed. The spectra were fitted by single lines and by the sum of two and three lines. The lines with Gaussian and Lorentzian shapes were used. The experimental EPR spectra of the burn wounds were fitted by theoretical lines as a superposition of two Gaussian lines (GG), two Lorentzian lines (LL), and by the sum of Gaussian and Lorentzian (GL) lines. The experimental spectra were fitted by the sum of three Gaussian Lines (GGG), three Lorentzian lines (LLL), two Gaussian lines and one Lorentzian line (GGL), and one Gaussian and two Lorentzian lines (GLL). The best fitting of the experimental EPR spectra of the burn wounds was recognized as the one giving the lowest value of the standard deviation (Bpp) and the percentage fractions of each component's line in the total EPR spectrum were determined. The fraction of the individual lines in the total spectrum was obtained as the percentage fraction of the integral intensity of these component's lines in the integral intensity of the total spectrum.The linewidths (Δfr(x), x = 1. N represents a discrete set of function values within domain  and time step ∆x = 10−3. The best match of fr function using fp function defined as a composition of basic functions was searched. The first derivative of microwave absorption function for radicals was taken into account. The signal was filtered before approximation and its reference point  was defined.The numerical procedure of the spectroscopic analysis is described below. The analysis of the complex signal, which is given as a time series Filtering of the signal was performed by moving an average filter and the filter based on fast Fourier transformation (FFT) , 18. Thefr according to x-  and y-  axes. To find the reference values, the following rules were used: (a) the sum of values of samples separated by x-axis is close to 0, and (b) the absolute value of the sum of function from left side of y-axis plus the absolute value of the sum of function from the right side of y were maximized. Finally, the filtered and shifted fr function is processed by the approximation algorithm. The Gaussian and Lorentzian functions were selected to the approximations. The genetic algorithm with [The reference point  was found by defining a horizontal and vertical shift of a filtered signal thm with  the conjthm with .Radicals and other paramagnetic molecules play an important role in both physiological and pathological conditions. Radicals are formed in burn wound matrix in thermolysis processes . As a reDifferent groups of radicals in the skin burn wounds have been found in our study.The experimental EPR spectrum of the burn wounds is shown in 225The numerical analysis of the spectral shape pointed out that the experimental EPR spectrum of the burn wounds was a superposition of the three lines Tables  and 2. TBpp) of their EPR signals. The parameters of the EPR lines of these groups of radicals are visible in A different chemical origin of each of the group of radicals was reflected in linewidths  line > narrow Lorentzian (L2) line > broad Lorentzian (L1) line . The high oxygen . These rThis work was a fine example of applying the electron paramagnetic resonance and the numerical procedures of the spectral lineshape analysis for identification of the complex radical system in tissues. The analysis of the total EPR spectra gives only information about the whole radicals system. The performed deconvolution of the resultant EPR spectra to the component lines allowed us to different groups of radicals in the biological samples.Our findings have significant implications since the healing of the burn wound remains a challenge to modern medicine. Oxidative stress could contribute to secondary tissue impairment and altered immune function after burn traumatic injury. Moreover, the study indicated various groups of radicals arising during the healing process of burn wounds which may modulate the transition of ECM components as well as influence the activity of the components participating in degradation by matrix metalloproteinases, thus contributing to controlling the healing process at cellular level and conditioning the formation of the favorable biochemical environment favoring an effective tissue repair , 25. DueThe numerical study of the lineshape of the complex EPR spectra was a helpful method for identification of the number of different groups of radicals in the burn wounds. These EPR spectra were superposition of three lines: broad Gaussian (G1) line, broad Lorentzian (L1) line, and narrow (L2) Lorentzian line. The modern spectral analysis was proposed. This method additionally gave information about the percentage contents of each type of radicals in the burn wounds. Radicals with weak dipolar interactions responsible for the narrow Lorentzian (L2) line existed mainly in the examined burn wounds.


In this work, an estimation of the relative yield losses of wheat due to ozone exposure is made by means of two approaches proposed by the CLRTAP (Convention on Long Range Transboundary Air Pollution): the exposure-response approach, which deals with the exposure of plants to ozone during a certain time, and the accumulated uptake approach, which, besides ozone exposure, deals with the velocity of absorption of the contaminant and the environmental factors that modulate that absorption. Once the relative yield losses are calculated by means of the two approaches, the aim is to establish which index (the exposure-response index or the accumulated uptake index) best characterizes the response of wheat plants to ozone. The relative yield losses are compared considering two watering regimes: well watered and nonwatered. The results obtained show that the relative yield losses in wheat due to ozone exposure are much more strongly linked to the real quantity of ozone absorbed by plants than to the environmental ozone exposure, which means that the accumulated uptake approach is much more realistic than the exposure-response approach. Relative yield loss estimations were higher in a crop with no watering; 3% of relative yield losses more than a crop watered until field capacity.


The involvement of the reticular formation (RF) in the transmission and modulation of nociceptive information has been extensively studied. The brainstem RF contains several areas which are targeted by spinal cord afferents conveying nociceptive input. The arrival of nociceptive input to the RF may trigger alert reactions which generate a protective/defense reaction to pain. RF neurons located at the medulla oblongata and targeted by ascending nociceptive information are also involved in the control of vital functions that can be affected by pain, namely cardiovascular control. The RF contains centers that belong to the pain modulatory system, namely areas involved in bidirectional balance (decrease or enhancement) of pain responses. It is currently accepted that the imbalance of pain modulation towards pain facilitation accounts for chronic pain. The medullary RF has the peculiarity of harboring areas involved in bidirectional pain control namely by the existence of specific neuronal populations involved in antinociceptive or pronociceptive behavioral responses, namely at the rostroventromedial medulla (RVM) and the caudal ventrolateral medulla (VLM). Furthermore the dorsal reticular nucleus  may enhance nociceptive responses, through a reverberative circuit established with spinal lamina I neurons and inhibit wide-dynamic range (WDR) neurons of the deep dorsal horn. The components of the triad RVM-VLM-DRt are reciprocally connected and represent a key gateway for top-down pain modulation. The RVM-VLM-DRt triad also represents the neurobiological substrate for the emotional and cognitive modulation of pain, through pathways that involve the periaqueductal gray (PAG)-RVM connection. Collectively, we propose that the RVM-VLM-DRt triad represents a key component of the “dynamic pain connectome” with special features to provide integrated and rapid responses in situations which are life-threatening and involve pain. The new available techniques in neurobiological studies both in animal and human studies are producing new and fascinating data which allow to understand the complex role of the RF in pain modulation and its integration with several body functions and also how the RF accounts for chronic pain. The involvement of the brainstem reticular formation (RF) in the transmission and modulation of pain is well established. A long path has been covered since the initial anatomical studies demonstrating that the RF projects to the thalamus, passing by the functional approaches showing that manipulation of the RF changes behavioral nociceptive responses and going through imaging studies in humans indicating activation of the RF in response to pain. The study of the role of the RF in pain is challenging due to anatomical and functional reasons. Anatomically, the RF is defined as an aggregation of neurons with several morphological configurations and without distinct connection pattern. Functionally, and besides the sensory component of pain, the RF is involved in a plethora of functions which include arousal, motor reactions, cardiovascular control and visceral functions. This anatomofunctional complexity of the RF deviated neuroscientists from a global study of the involvement of the RF in pain processing and most studies have been directed to specific areas of the RF. Taking into account the concept that pain control cannot be studied apart from other brain functions and also the intrinsic feature of the RF as the brain network, by excellence, it is possible that the RF represents an outstanding example of the “dynamic pain connectome” , the caudal ventrolateral medulla (VLM) and the dorsal reticular nucleus . After reviewing the anatomofunctional features of the involvement of each area in pain transmission and modulation, we then discuss how the triad RVM-VLM-DRt plays a key role as a gateway to allow pain modulation from the brain to target the spinal cord, i.e., top-down modulation Figure . The rolThe involvement of the spinoreticulothalamic pathway as a major ascending pathway for nociceptive transmission to the brain is well established. Overall this multisynaptic pathway originated from neurons mainly located in the spinal cord laminae IV–V and VII–VIII targets areas of the medullary and pontine RF which have collaterals of the spinothalamic tract  is involved in stimulation-produced analgesia  anatomical location; (ii) connections with the spinal cord; (iii) nociceptive control; and (iv) local neurochemical systems.The RVM includes the midline located nucleus raphe-magnus (NRM) and the adjacent RF in the vicinity of the nucleus reticularis gigantocellularis. In what concerns its involvement in pain modulation, these anatomical components of the RVM are frequently considered together inasmuch that local modulation techniques, such as electrical or chemical stimulation, do not allow a precise discrimination of the NRM from the adjacent RF. Rostrocaudally, the RVM extends from the pontomedullary junction to the level of appearance of the pyramidal decussation.The ascending projections from the spinal cord to the RVM are very scarce. The descending input from the RVM to the spinal cord is prominent and targets almost all spinal segments, reaching mainly the dorsal horn (laminae I–V) but also lamina X Millan, . As to tThe involvement of the RVM as a crucial relay station from the pain modulatory actions arising from the PAG is well established  and the lateral reticular nucleus (LRt) and appears to play a specific role in pain modulation , dorsomedially, the Sp5C, laterally and the VLM, ventrally , allowing to investigate more accurately the spinal cord as well as the brainstem, also confirm the involvement of the DRt in pain processing , a mechanism of top-down inhibitory control of spinal dorsal horn neurons  are interconnected Figure . The VLMThe RVM-VLM-DRt triad is in a privileged position to collect input from higher brain centers and convey this modulation to the spinal cord Figure . The RVM5 and A7 , the technical problems of studying small components may be surpassed as the triad should be considered as a gateway from the brain to the spinal cord. The RVM-VLM-DRt triad probably represents an example of the “brain pain connectome” and should not be analyzed as to its individual components, IT was responsible for the overall organization of the manuscript and wrote the parts related to the rostroventromedial medulla and the ventrolateral medulla. IM was responsible for the items related to the role of the dorsal reticular nucleus. The overall manuscript was reviewed by both authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer ES and handling Editor declared their shared affiliation, and the handling Editor states that the process nevertheless met the standards of a fair and objective review.


Tendons feature the crucial role to transmit the forces exerted by the muscles to the skeleton. Thus, an increase of the force generating capacity of a muscle needs to go in line with a corresponding modulation of the mechanical properties of the associated tendon to avoid potential harm to the integrity of the tendinous tissue. However, as summarized in the present narrative review, muscle and tendon differ with regard to both the time course of adaptation to mechanical loading as well as the responsiveness to certain types of mechanical stimulation. Plyometric loading, for example, seems to be a more potent stimulus for muscle compared to tendon adaptation. In growing athletes, the increased levels of circulating sex hormones might additionally augment an imbalanced development of muscle strength and tendon mechanical properties, which could potentially relate to the increasing incidence of tendon overload injuries that has been indicated for adolescence. In fact, increased tendon stress and strain due to a non-uniform musculotendinous development has been observed recently in adolescent volleyball athletes, a high-risk group for tendinopathy. These findings highlight the importance to deepen the current understanding of the interaction of loading and maturation and demonstrate the need for the development of preventive strategies. Therefore, this review concludes with an evidence-based concept for a specific loading program for increasing tendon stiffness, which could be implemented in the training regimen of young athletes at risk for tendinopathy. This program incorporates five sets of four contractions with an intensity of 85–90% of the isometric voluntary maximum and a movement/contraction duration that provides 3 s of high magnitude tendon strain. Tendinopathy is a clinical condition that is associated with pathological processes within the tendon and pain  radial adaptation, (b) longitudinal adaptation and (c) adaptation of specific tension . The role of metabolic stress for muscle growth in response to exercise has been attributed to the associated systemic growth-related hormone and local myokine up-regulation and/or the increased fiber recruitment with muscle fatigue  for load application does on the other hand not seem to be of particular relevance for the adaptive response .Aside from mechanical loading, maturation induces profound changes of the skeletal, neuromuscular and tendinous system in young athletes. The following section briefly reviews muscle and tendon development from child to adulthood, then focuses on somatic and hormonal changes that might challenge the balance of the development of muscle and tendon properties. The section closes with a synopsis of recent experimental evidence of an imbalanced muscle and tendon development in adolescent athletes.Whole body muscle mass increases progressively from childhood to adulthood, with a pronounced rise during adolescence, especially in boys  maturation and (b) a predominantly plyometric loading profile can lead to a musculotendinous imbalance that increases the load  and internal demand  for the tendon. Mersmann et al.  comparedCollectively, the evidence reviewed in this chapter strongly suggests that muscle and tendon show differences in the time course of adaptation to mechanical loading and in the types of mechanical stimulation that effectively elicits adaptive processes. Maturation acts as an additional stimulus on the muscle-tendon unit of young athletes and could further contribute to a development of an imbalance of muscle strength and tendon stiffness. Adolescence could be a critical phase in that context due to the associated increase of sex hormones. However, the interplay of mechanical loading and changes of the hormonal milieu on muscle and tendon plasticity in general, and with regard to adolescence in particular, is still largely unknown. Similarly, though recent evidence demonstrated that an imbalanced musculotendinous adaptation can occur during adolescence . Though tendinopathy has certainly a multifactorial etiology, the mechanical strain theory is currently considered the most probable injury mechanism and attributes the histological, molecular and functional changes of the affected tissue to mechanical overload  the resultant increased mechanical demand is a candidate mechanism to induce overload, (b) the prevalence of soft-tissue overuse injuries is high at time-points in the training process  and in sport disciplines that favor the development of a muscle-tendon imbalance from a mechanobiological point of view, and (c) maturation seems to be a potential risk factor for the development of both tendinopathy and musculotendinous imbalances in young athletes. There certainly is a need to provide more direct support for an association between imbalanced muscle and tendon adaptation and overuse. Yet, it appears that the interaction of maturation with mechanical loading could potentially increase the likelihood of the occurrence of such imbalances, which in turn might be related to the increasing risk of tendon overuse in adolescence. However, these assumptions need to be supported by further research.Following the hypothesis that an imbalanced development of muscle strength and tendon stiffness could increase the risk for tendon overuse injury, it might be promising to target the increase of tendon stiffness in groups at risk . The following chapter provides evidence-based suggestions for an effective tendon training and comments on open issues. The chapter concludes with a critical discussion of the current evidence on the effects of preventive interventions outlines the anticipated effects of an intervention-induced increase of tendon stiffness on athletic performance.in vivo (see section Mechanotransduction in Tendon) suggests that both contraction intensity and contraction duration need to exceed a certain threshold to provide an efficient training stimulus. The training intensity is considered to be optimal around 85–90% of iMVC and the contraction duration around 3 s  the risk of tendon injury and (b) athletic performance. A recent systematic review on the effects of preventive interventions for tendinopathy concluded that evidence for their efficacy is only limited (Peters et al., Aside from the potentially beneficial effects for the health of young athletes, tendon stiffness and the interaction of muscle and tendon during movement are important contributors to movement performance. For example, increased tendon stiffness is associated with a lower electromechanical delay, a greater rate of force development and jump height (Bojsen-Møller et al., Current scientific evidence strongly supports the idea that the development of muscle strength during a training process is not necessarily accompanied by an adequate modulation of tendon stiffness. The differences in the time course of adaptation and in the mechanical stimuli that trigger adaptive processes provide two mechanisms that can account for a dissociation of the muscular and tendinous development. Though the additional influence of maturation is still a heavily under-investigated topic, it is likely that an imbalanced development of muscle strength and tendon stiffness is a relevant issue for youth sports and it seems that the risk might even be increased compared to adults. Adolescence, with its associated somatic and endocrine processes, could be a critical phase in that regard. Due to the mechanical loading profile, musculotendinous imbalances especially concern athletes from jump disciplines and the high prevalence of tendinopathy in those sports as well as the increasing incidence during adolescence support the hypothesis that imbalances of muscle strength and tendon stiffness could have implications for the health of young athletes. The implementation of interventions targeting the improvement of tendon mechanical properties could be a promising approach to prevent such imbalances, promote athletic performance and reduce the risk of tendon injury. However, there is still a clear lack of information on the time course of changes of the musculotendinous system during premature development and the interaction of maturation and mechanical loading. The effects of changing sex hormone levels on tendon properties and plasticity is also widely unknown. Similarly, the association of musculotendinous imbalances with tendon overuse injury as well as the preventive value of interventions that promote the development of tendon mechanical properties has not been established thus far. The effects of recovery for tendon adaptation in general are largely unexplored and a future challenge with regard to the application of preventive tendon training in youth sports is the determination of age-specific dose-response relationships and the implementation in the training schedule in elite sports. The increasing prevalence of tendinopathy in athletic adolescents certainly calls for further research on these issues.All authors substantially contributed to the interpretation of the literature addressed in this review. FM drafted and finalized the manuscript. SB and AA made important intellectual contributions in revision of all sections of the manuscript. AA supervised the preparation of the manuscript. All authors approved the final version of the manuscript and agree to be accountable for the content of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.