Relapse in resected lung cancer revisited: does intensified follow up really matter? A prospective study

<p>Abstract</p> <p>Background</p> <p>beside the well known predominance of distant vs. loco-regional relapse, several aspects of the relapse pattern still have not been fully elucidated.</p> <p>Methods</p> <p>prospective, controlled study on 88 patients operated for non-small cell lung cancer (NSCLC) in a 15 months period. Stage IIIA existed in 35(39.8%) patients, whilst stages IB, IIA and IIB existed in 10.2%, 4.5% and 45.5% patients respectively. Inclusion criteria: stage I-IIIA, complete resection, systematic lymphadenectomy with at least 6 lymph node groups examined, no neoadjuvant therapy, exact data of all aspects of relapse, exact data about the outcome of the treatment.</p> <p>Results</p> <p>postoperative lung cancer relapse occurred in 50(56.8%) patients. Locoregional, distant and both types of relapse occurred in 26%, 70% and 4% patients respectively. Postoperative cancer relapse occurred in 27/35(77.1%) pts. in the stage IIIA and in 21/40(52.55) pts in the stage IIB. In none of four pts. in the stage IIA cancer relapse occurred, unlike 22.22% pts. with relapse in the stage IB. The mean disease free interval in the analysed group was 34.38 ± 3.26 months.</p> <p>The mean local relapse free and distant relapse free intervals were 55 ± 3.32 and 41.62 ± 3.47 months respectively Among 30 pts. with the relapse onset inside the first 12 month after the lung resection, in 20(66.6%) pts. either T3 tumours or N2 lesions existed. In patients with N0, N1 and N2 lesions, cancer relapse occurred in 30%, 55.6% and 70.8% patients respectively</p> <p>Radiographic aspect T stage, N stage and extent of resection were found as significant in terms of survival. Related to the relapse occurrence, although radiographic aspect and extent of resection followed the same trend as in the survival analysis, only T stage and N stage were found as significant in the same sense as for survival. On multivariate, only T and N stage were found as significant in terms of survival.</p> <p>Specific oncological treatment of relapse was possible in 27/50(54%) patients.</p> <p>Conclusion</p> <p>the intensified follow up did not increase either the proportion of patients detected with asymptomatic relapse or the number of patients with specific oncological treatment of relapse.</p

Endocytosis and lysosomal degradation of GluA2/3 AMPARs in response to oxygen/glucose deprivation in hippocampal but not cortical neurons

Abstract Global cerebral ischemia results in oxygen and glucose deprivation (OGD) and consequent delayed cell death of vulnerable neurons, with hippocampal CA1 neurons more vulnerable than cortical neurons. Most AMPA receptors (AMPARs) are heteromeric complexes of subunits GluA1/GluA2 or GluA2/GluA3, and the presence of GluA2 renders AMPARs Ca2+-impermeable. In hippocampal CA1 neurons, OGD causes the synaptic expression of GluA2-lacking Ca2+-permeable AMPARs, contributing to toxic Ca2+ influx. The loss of synaptic GluA2 is caused by rapid trafficking of GluA2-containing AMPARs from the cell surface, followed by a delayed reduction in GluA2 mRNA expression. We show here that OGD causes endocytosis, lysosomal targeting and consequent degradation of GluA2- and GluA3-containing AMPARs, and that PICK1 is required for both OGD-induced GluA2 endocytosis and lysosomal sorting. Our results further suggest that GluA1-containing AMPARs resist OGD-induced endocytosis. OGD does not cause GluA2 endocytosis in cortical neurons, and we show that PICK1 binding to the endocytic adaptor AP2 is enhanced by OGD in hippocampal, but not cortical neurons. We propose that endocytosis of GluA2/3, caused by a hippocampal-specific increase in PICK1-AP2 interactions, followed by PICK1-dependent lysosomal targeting, are critical events in determining changes in AMPAR subunit composition in the response to ischaemia

Spela plattformsspel som hemläxa – spel med fokus på läromaterial enligt läroplanen

Det finns många positiva aspekter med spel i undervisningen, bland annat kan det bidra till ökad motivation och engagemang. Men det finns också många hinder, det kan krävas mycket tid av läraren för att sätta sig in i och lära sig hantera ett specifikt spel och det kan vara svårt att anpassa ett spel till läroplanen, vilket i sin tur kan göra undervisningen långsammare och ineffektiv. Denna studie syftar till att undersöka om huruvida läxläsning kan utföras med hjälp av digitala spel på ett effektivt och roligt sätt. Rapporten beskriver ett spel där läraren kan anpassa innehållet efter läroplanen. Spelet innebär att eleverna gör läxorna genom att spela spelet och lärare kan automatiskt ta del av elevernas resultat och anpassa undervisningen därefter. Resultatet visade att konceptet uppskattades både av de deltagande eleverna samt läraren. Den inledande prototypen fokuserar enbart på matematik.There are many positive things about using games in education, for instance it can improve both motivation and commitment. But there are also a lot of obstacles, it might require the teacher to spend a lot of time to engage with a game and learn a specific game and it might be hard to customize the game’s content according to the curriculum which could make the tuition slow and ineffective. This study’s purpose is to investigate whether the homework can be performed while playing digital games in a efficient and fun way. The report describes a game where the teacher can customize the content according to the curriculum. The idea is to make it possible for students to do their homework while playing this game and the teachers will automatically be able to receive the results and customize the tuition according to it. The initial prototype will focus on the subject math

Spela plattformsspel som hemläxa – spel med fokus på läromaterial enligt läroplanen

Det finns många positiva aspekter med spel i undervisningen, bland annat kan det bidra till ökadmotivation och engagemang. Men det finns också många hinder, det kan krävas mycket tid av läraren föratt sätta sig in i och lära sig hantera ett specifikt spel och det kan vara svårt att anpassa ett spel tillläroplanen, vilket i sin tur kan göra undervisningen långsammare och ineffektiv. Denna studie syftar tillatt undersöka om huruvida läxläsning kan utföras med hjälp av digitala spel på ett effektivt och roligt sätt.Rapporten beskriver ett spel där läraren kan anpassa innehållet efter läroplanen. Spelet innebär atteleverna gör läxorna genom att spela spelet och lärare kan automatiskt ta del av elevernas resultat ochanpassa undervisningen därefter. Resultatet visade att konceptet uppskattades både av de deltagandeeleverna samt läraren. Den inledande prototypen fokuserar enbart på matematik.There are many positive things about using games in education, for instance it can improve bothmotivation and commitment. But there are also a lot of obstacles, it might require the teacher to spend alot of time to engage with a game and learn a specific game and it might be hard to customize the game’scontent according to the curriculum which could make the tuition slow and ineffective. This study’spurpose is to investigate whether the homework can be performed while playing digital games in aefficient and fun way. The report describes a game where the teacher can customize the content accordingto the curriculum. The idea is to make it possible for students to do their homework while playing thisgame and the teachers will automatically be able to receive the results and customize the tuition accordingto it. The initial prototype will focus on the subject math

Spela plattformsspel som hemläxa – spel med fokus på läromaterial enligt läroplanen

Det finns många positiva aspekter med spel i undervisningen, bland annat kan det bidra till ökadmotivation och engagemang. Men det finns också många hinder, det kan krävas mycket tid av läraren föratt sätta sig in i och lära sig hantera ett specifikt spel och det kan vara svårt att anpassa ett spel tillläroplanen, vilket i sin tur kan göra undervisningen långsammare och ineffektiv. Denna studie syftar tillatt undersöka om huruvida läxläsning kan utföras med hjälp av digitala spel på ett effektivt och roligt sätt.Rapporten beskriver ett spel där läraren kan anpassa innehållet efter läroplanen. Spelet innebär atteleverna gör läxorna genom att spela spelet och lärare kan automatiskt ta del av elevernas resultat ochanpassa undervisningen därefter. Resultatet visade att konceptet uppskattades både av de deltagandeeleverna samt läraren. Den inledande prototypen fokuserar enbart på matematik.There are many positive things about using games in education, for instance it can improve bothmotivation and commitment. But there are also a lot of obstacles, it might require the teacher to spend alot of time to engage with a game and learn a specific game and it might be hard to customize the game’scontent according to the curriculum which could make the tuition slow and ineffective. This study’spurpose is to investigate whether the homework can be performed while playing digital games in aefficient and fun way. The report describes a game where the teacher can customize the content accordingto the curriculum. The idea is to make it possible for students to do their homework while playing thisgame and the teachers will automatically be able to receive the results and customize the tuition accordingto it. The initial prototype will focus on the subject math

Identification of local stress parameters influencing the optimum design of box girders

Research into the effect of local stress on the carrying capacity and optimum design of box girders was performed in this paper. A mathematical model of the girder was created for the purpose of defining the stress-strain state of local character. Mathematical dependence which defines the length of the influential zone in box girders was established. The segment length relevant for the analysis of local stress is functionally dependent on geometrical parameters of the girder cross section, area of action and size of load. The methodology carried out in this paper showed that the identification of local stress can be performed only on a segment of the girder. The procedure of calculation and experimental determination of the local stress state in carrying structures was thus considerably simplified, without reducing accuracy. The influential parameters were identified and the guidelines for optimum design of quadrilateral shape of the girder cross section were given from the aspect of local stress. The comparative analysis was used to establish, under the same conditions of global carrying capacity, a more favourable stress state in trapezoidal shape in comparison with the traditional rectangular cross section of the girder. Application of the results of this paper is a contribution to the process of optimal design of supporting structures, especially those that are used for construction of transport equipment and rack structures in storage systems, where the effect of reducing the weight affects on the efficiency of transport in supply chains. © 2012 Elsevier Ltd

Factors that could influence the severity of post-traumatic lung fat embolism - a prospective histological study -

INTRODUCTION Each fracture of long or pelvic bones as well as large contusions of subcutaneous fat tissue cause releasing of fat globules that rapidly penetrate into circulation through the ruptured veins of the injured tissue, and reach the lung circulation [1,2]. During the first phase, fat emboli block the functional lung circulation by their mechanical effect in capillaries producing so called isolated post-traumatic lung fat embolism [3]. The surface layer of a fat embolus, which is practically in liquid state, behaves as a membrane of very high density, i.e., as it is under high pressure which obstruct the blood stream [4] that is finally stopped at the level of lung blood vessels with diameter of approximately 20 µ [5].This pathophysiological mechanism produces cor pulmonale acutum, with poor pathological findings [8]. Nowadays, the post-mortem diagnosis of lung fat embolism is based on microscopical examination of tissue specimens, usually prepared with special histological staining (Sudan III) [9]. The grading of fat embolism according to Sevitt's criteria is generally accepted [10]. Taking of slices from apicoventral areas of the lungs has been recommended [11]. With longer outliving period, the total number of fat emboli in the lung circulation gradually decreases, due to their disintegration and resorption. It has been stated that fat globules completely disappear about 4-6 weeks after injury, and that they should not be searched for microscopically in this post-traumatic phase [11]. OBJECTIVES The aim of our work was to determine whether the age of injured, their gender, total severity of trauma, outliving period, and hypovole-mic shock that develops after injuring, may induce development of more severe forms of post-traumatic lung fat embolism. MATERIAL AND METHODS A prospective histological study was performed on the autopsy material of the Institute of Forensic Medicine in Belgrade. The analyzed sample consisted of individuals with injuries that might be a source of fat emboli (fractures of long bones, large contusions of subcutaneous fat tissue). The lung slices were systematically taken and stained with special fat staining (Sudan III). In each particular case, the grade of lung fat embolism was counted on the basis of microscopical appearance, according to Sevitt's criteria. The total severity of trauma was estimated by calculation of the Injury Severity Score (ISS) [13,14]. In no cases from the analyzed sample, the fat embolism was mentioned as either singular or plural cause of death. The obtained results were analyzed by means of appropriates statistical methods (ANOVA LSD-test, x2 test, Man-Whitney test, Fischer's test of correct probability). RESULTS AND DISCUSSION The analyzed sample included 58 fatally injured individuals, 39 males and 19 females. The average age was 54.10 years (SD=16.56), the average value of ISS was 34.69 (SD=5.88), and the average outliving period was 3.74 days (SD=5.88). However, all these data look differently when the analyzed sample has been stratified and analyzed according to the estimated grade of lung fat embolism. It was not showed that severity of lung fat embolism depends on sex of the injured (^2=0.842 p&gt;0.05). The groups with the slightest and the most severe grade of lung fat embolism are statistically significantly different in relation to age of individuals (ANOVA, p=0.017). By means of LSD test, it has been showed that the group with the most severe grade of lung fat embolism (grade III) is statistically significantly different comparing to other two groups (with grade I and II) in relation to the age of injured (the values are p=0.16 and p=0.19 respectively, and the both groups are less than p=0.05). In the group with the most severe grade of lung fat embolism, the older individuals are statistically significantly represented comparing to othertwo groups. CONCLUSION The analysis of our sample showed that the most severe grade of post-traumatic lung fat embolism (microscopical grade III according to Sevitt's criteria) was determined in older individuals, more severely injured, and with shorter outliving period. The severity of fat embolism depends neither on sex of the injured, nor on development of post-traumatic hypovolemic shock. The obtained results related to the influence of hypovolemic shock on severity of fat embolism should be accepted with a caution. Namely, sometimes there is an intention to simplify a procedure of creating of autopsy conclusion about the cause of death, so that loss of blood is not mentioned at all, in spite of fact that it could have been a concurrent cause of death, while in other cases exsanguination is designated as a sole cause of death, forgetting the possibility that fat embolism could have really been the immediate cause of death