Background: Irritable bowel syndrome (IBS) is an extremely common condition affecting approximately 10-15% of the population. Lower abdominal pain is a common feature and, if the patient also has gynaecological symptoms such as heavy periods, they may be referred to a gynaecologist especially when the bowel symptoms are relatively mild. In this setting a laparoscopy is often undertaken and endometriosis commonly identified as this condition affects up to 10% of women. Consequently pain is frequently attributed to the endometriosis even when it is relatively mild. However it is a common observation amongst gynaecologists that women with mild endometriosis often have severe symptoms which do not seem to respond well to treatment. This raises the possibility that their pain may not actually be due to endometriosis or is being amplified by the visceral hypersensitivity which is a characteristic feature of irritable bowel syndrome.Methods: 20 patients with minimal-mild endometriosis, 20 with moderate-severe endometriosis, 20 healthy volunteers (HV) who have had laparoscopy for sterilisation, 20 IBS patients and 20 patients with pain who were found to have a normal pelvis (on laparoscopy) were studied. Gastrointestinal, gynaecological, and noncolonic symptoms were recorded as well as demography, quality of life and psychological status. Visceral sensitivity was assessed in all patients and abdominal distension was studied in a sub group of 26 endometriosis patients and 20 IBS patients.Results: 20 (100%) of IBS patients, 13 (65%) of minimal-mild endometriosis patients, 11 (55%) of moderate-severe endometriosis patients, 17 (85%) of laparoscopic negative pain patients and no healthy volunteers fulfilled ROME III criteria for IBS. Patients with endometriosis and IBS had similar levels of visceral sensitivity which were significantly lower than that observed in controls (p=0·002, p<0·001).In particular, both minimal-mild and moderate-severe endometriosis patients had significantly lower (mean-95% CI) pain thresholds in mmHg 28.1(24.5, 31.6) and 28.8(24.9, 32.6) respectively compared with controls 39·5 (36·0, 43·0) p=0.001and p=0.002. However, with few exceptions, there were no distinguishing features between patients in terms of demography, symptomatology and distension.Conclusion: Clinically, it is very difficult to distinguish between endometriosis and IBS. However, visceral hypersensitivity appears to be a major component of endometriosis and may explain the problem of excessive pain especially in patients with mild disease offering a potential new target for treatment

No description available.

Correct understanding of passive force behavior is particularly key to lateral evaluations of bridges because plastic deformation of soil backfill is vital to dissipation of earthquake energy and thermally-induced stresses in abutments. Only recently have studies investigated the effects of skew on passive force. Numerical modeling and a handful of skewed abutment tests performed in sand backfill have found reduced passive force with increasing skew, but previous to this study no skewed tests had been performed in gravel or Geosynthetic Reinforced Soil (GRS) backfills. The goal of this study was to better understand passive force behavior in non-skewed and skewed abutments with gravel and GRS backfills. Prior to this study, passive pressures in a GRS integrated approach had not been investigated. Gravel backfills also lack extensive passive force tests.Large-scale testing was performed with non-skewed and 30° skewed abutment configurations. Two tests were performed at each skew angle, one with unconfined gravel backfill and one with GRS backfill, for a total of four tests. The test abutment backwall was 11 ft (3.35 m) wide, non-skewed, and 5.5 ft (1.68 m) high and loaded laterally into the backfill. However, due to actuator loading constraints, all tests except the non-skewed unconfined gravel test were performed to a backfill height of 3.5 ft (1.07 m). The passive force results for the unconfined gravel test was scaled to a 3.5 ft (1.07 m) height for comparison.Test results in both sets of backfills confirmed previous findings that there is significant reduction in passive force with skewed abutment configurations. The reduction factor was 0.58 for the gravel backfill and 0.63 for the GRS backfill, compared to the predicted reduction factor of 0.53 for a 30° skew. These results are within the scatter of previous skewed testing, but could indicate that slightly higher reduction factors may be applicable for gravel backfills. Both backfills exhibited greater passive strength than sand backfills due to increased internal friction angle and unit weight. The GRS backfill had reduced initial stiffness and only reached 79% to 87% of the passive force developed by the unreinforced gravel backfill. This reduction was considered to be a result of reduced interface friction due to the geotextile. Additionally, the GRS behaved more linearly than unreinforced soil. This backfill elasticity is favorable in the GRS-Integrated Bridge System (GRS-IBS) abutment configuration because it allows thermal movement without developing excessive induced stresses in the bridge superstructure.

Naturally, maritime training simulators at all events are valuable instructional and pedagogical tools. Through the history, the maritime simulation was utilized to train prospective maritime apprentices in whom it has filled the gap left by the acute shortage of opportunities for jobs onboard vessels around the globe. However, professional seafarers are the axis of success and competitiveness in the field of maritime training. They are the ones that, who are well trained and have the responsibilities of their work and the surrounding environment. In order to achieve the success along with effective training skills, both maritime companies and seafarers should implement a management of safety onboard ships, which only can be executed through the effective usage of the Bridge Resource Management (BRM) and righteous maritime simulation training. Qualitative upgrading of the maritime training process at higher education levels depends predominantly on the instructive value of the instructors' educational software and the content of these programs which contains advanced and intelligent scenarios that benefit positively in providing effective training in order to, transfer and implement their gained skills from virtual reality to the actual environment with minimal risks and additionally to avoid the unforeseen occurrences at sea. The outcomes of the evaluation have shown the instructional suitability of the maritime educational scheme and significant capabilities, it provides, as well as the domains and frameworks for its instructional development. The above facts are substantial in the refinement and improvement of the current maritime education and growth of the apprentices' capabilities and the professionalism of their skills, along with the farthest purpose of creating more educated marine navigators in the worldwide merchant fleet. This research proposes and demonstrates in details the purpose of the maritime simulation training complexes, the elements that if provided, will lead to an effective maritime simulation training, types of maritime simulation, the International Maritime Organization (IMO), its tools and its power for the effectiveness of the maritime simulation training through different conventions & codes and the future for the maritime simulation training, in order to emphasize and accentuate the interplay between instructors and apprentices in an integrated maritime simulation complex on which a serious maritime event is taking place. The distillation of this thesis draws an attention to the effectiveness of the partnership between maritime apprentices and their instructors across a maritime simulation training complex scheme during a virtual maritime scenario event in an advanced facilities located in the state of Florida, which is armed with modern technology, provides both added stimulation for the apprentice himself and elevates the simulator a degree toward a vessel for practical training and/or sailing.

Background: IBS is the most common functional gastrointestinal disorders and affects approximately 10-20 % of the general population and is widespread in all societies and socio-economic groups. Although the disorder does not have a life-threatening course, it still seriously affects the patients in their everyday life. Aim: The general aims of this thesis were to estimate the occurrence of irritable bowel syndrome in the general population and to achieve a better understanding of present treatment of this disorder and impact on every-day life in those suffering from IBS. Material and methods: The LIPS study comprises two parts. Part I was a retrospective register study where the data collection was based on computerised medical records at three selected Primary Health Care centres in a defined region. Part II was a population based case-control study. The identified IBS cases from part I constitute the cases, while their control groups were randomly selected from the population census register in the same area as the cases. Data in part II were collected by means of a postal questionnaire to cases and controls. The study was conducted in Linköping, a city located in the south-east of Sweden with 135 000 inhabitants. Results: The female IBS patients reported lower influence on planning their work and working hours as well as fewer opportunities to learn new things at their work compared to their controls, even after adjustments in multiple logistic regressions for potential confounders like; mood, sleeping problems and perceived health. The female IBS patients had considerably lower HRQOL in all dimensions compared to their controls, even when compared to male patients. Younger female IBS cases (18-44 years) reported lower mental health on the SF-36 scale than the older IBS female cases (p=0.015). In the multivariate analysis these variables, lack of influence on planning the work, family history of IBS, anxiety and sleeping disturbance displayed an association with being diagnosed with IBS in women. In men, lack of influence on working pace, family history of IBS was associated with an IBS diagnosis.The consultation incidence of IBS in part I was 3.4 (95% CI 3.20-3.70) per 1000 person-years for all IBS cases, among females; the incidence rate was 4.6 per 1000 person-years (95% CI 4.16-4.97) and males; 2.3 per 1000 person-years (95% CI 2.01-2.59). The dominating pharmacological treatment prescribed for abdominal complaints were fibre and bulking laxatives agents as well as acid suppressive drugs. These variables had an independent impact on the probability of a follow-up consultation; diagnosed co-morbidity besides the IBS diagnosis, rectoscopy ordered and laboratory tests ordered. Conclusions: IBS patients identified in primary care are significantly affected in their working-life compared to individuals in the general population. Especially female IBS-patients report lower decision latitude at work and they also appear to have a particularly impaired psychosocial functioning in their every day life and impaired HRQOL. Factors associated with IBS diagnosis among females are anxiety as well as family history of IBS and lack of co-determination at work. The incidence rate of IBS was 3.4 per 1000 person-years which increased with age and with an overrepresentation of females. IBS patients did not appear to be heavy utilisers of primary care and those who attended were treated by their GP without further consultation. The strongest predictors for having a follow-up consultation were diagnosed co-morbidity, rectoscopy and laboratory tests ordered / Figure on page 8 reprinted from Lancet 360(9332), Nicholas, J Talley and Robin Spiller, "Irritable bowel syndrome: a little understood organic bowel disease?", pp. 555-564, Copyright 2006 with permission from Elsevier. On the day of the public defence of the doctoral thesis, the status of articles III and IV was Submitted.

Self-organization of regular surface pattern under ion beam erosion was described in detail by Navez in 1962. Several years later in 1986 Bradley and Harper (BH) published the first self-consistent theory on this phenomenon based on the competition of surface roughening described by Sigmund’s sputter theory and surface smoothing by Mullins-Herring diffusion. Many papers that followed BH theory introduced other processes responsible for the surface patterning e.g. viscous flow, redeposition, phase separation, preferential sputtering, etc. The present understanding is still not sufficient to specify the dominant driving forces responsible for self-organization. 3D atomistic simulations can improve the understanding by reproducing the pattern formation with the detailed microscopic description of the driving forces. 2D simulations published so far can contribute to this understanding only partially. A novel program package for 3D atomistic simulations called trider (TRansport of Ions in matter with DEfect Relaxation), which unifies full collision cascade simulation with atomistic relaxation processes, has been developed. The collision cascades are provided by simulations based on the Binary Collision Approximation, and the relaxation processes are simulated with the 3D lattice kinetic Monte-Carlo method. This allows, without any phenomenological model, a full 3D atomistic description on experimental spatiotemporal scales. Recently discussed new mechanisms of surface patterning like ballistic mass drift or the dependence of the local morphology on sputtering yield are inherently included in our atomistic approach. The atomistic 3D simulations do not depend so much on experimental assumptions like reported 2D simulations or continuum theories. The 3D computer experiments can even be considered as ’cleanest’ possible experiments for checking continuum theories. This work aims mainly at the methodology of a novel atomistic approach, showing that: (i) In general, sputtering is not the dominant driving force responsible for the ripple formation. Processes like bulk and surface defect kinetics dominate the surface morphology evolution. Only at grazing incidence the sputtering has been found to be a direct cause of the ripple formation. Bradley and Harper theory fails in explaining the ripple dynamics because it is based on the second-order-effect ‘sputtering’. However, taking into account the new mechanisms, a ‘Bradley-Harper equation’ with redefined parameters can be derived, which describes pattern formation satisfactorily. (ii) Kinetics of (bulk) defects has been revealed as the dominating driving force of pattern formation. Constantly created defects within the collision cascade, are responsible for local surface topography fluctuation and cause surface mass currents. The mass currents smooth the surface at normal and close to normal ion incidence angles, while ripples appear first at θ ≥ 40°. The evolution of bimetallic interfaces under ion irradiation is another application of trider described in this thesis. The collisional mixing is in competition with diffusion and phase separation. The irradiation with He+ ions is studied for two extreme cases of bimetals: (i) Irradiation of interfaces formed by immiscible elements, here Al and Pb. Ballistic interface mixing is accompanied by phase separation. Al and Pb nanoclusters show a self-ordering (banding) parallel to the interface. (ii) Irradiation of interfaces by intermetallics forming species, here Pt and Co. Well-ordered layers of phases of intermetallics appear in the sequence Pt/Pt3Co/PtCo/PtCo3/Co. The trider program package has been proven to be an appropriate technique providing a complete picture of mixing mechanisms.

Introduction. Les désordres de la connexion intestin-cerveau (DCIC) sont une association de symptômes digestifs récurrents et chroniques. Les évènements traumatiques précoces seraient un facteur déclenchant. Nous avons testé l’hypothèse selon laquelle la prématurité et les facteurs néonataux influencent le développement des DCIC. L’influence des facteurs socio-démographiques ou psychosociaux a aussi été évaluée. Patients et Méthodes. Une étude cas-témoins a été menée au CHU Sainte Justine à Montréal (Québec, Canada) de juillet 2019 à juillet 2021. Les cas (adultes nés avant 29 semaines d’aménorrhée) ont été recrutés dans la cohorte HAPI (Health of Adults Born Preterm Investigation). Les contrôles sont issus de la population générale. Les participants ont complété le questionnaire de diagnostic Rome IV. Les cas ont complété des questionnaires de dépression et d’anxiété (PROMIS-29, GAD-7, PHQ-9). Résultats. 79 cas (âge médian : 27 ans (24;29), sex ratio H/F: 0.4) et 124 contrôles (âge médian : 33 ans (27;50), sex ratio H/F: 0.9) ont été recrutés. Les prévalences des désordres fonctionnels gastroduodénaux et intestinaux étaient significativement plus élevées dans le groupe des cas féminins comparé aux contrôles féminins, respectivement p=0.017 et p=0.015. La probabilité d’avoir au moins un désordre fonctionnel intestinal ou une constipation fonctionnelle était plus élevé dans ce dernier groupe (p=0.015 et p=0.02). Certains facteurs de risque de développer des DCIC sont directement liés à la prématurité (chorioamniotite, hémorragie intra-ventriculaire) ou à une conséquence de la prématurité (anxiété, dépression, capacités sociales). Conclusion. Il s’agit de la première étude contrôlée qui rapporte la prévalence des DCIC dans une population d’adultes nés prématurés. Nous confirmons que la prématurité est un facteur de risque de développement du DCIC au cours de la vie. / Background. Disorders of brain-gut interaction (DBGI) are defined as a variable combination of chronic or recurrent gastrointestinal symptoms. Early-life stress have been implicated as possible contributing factor. We tested the hypothesis that prematurity and neonatal factors influence the development of DGBI in adults. We also evaluated if sociodemographic or psychosocial factors are associated with the development of a DGBI. Methods. A case-control study was carried out at the Centre Hospitalier Universitaire Sainte-Justine in Montreal (Quebec, Canada) from July 2019 to July 2021. The cases (adults born with severe or extremely severe prematurity born less than 29 weeks of gestation) were recruited from the Health of Adults Born Preterm Investigation (HAPI) cohort. Control subjects were recruited from the general population. All participants completed the Rome IV diagnostic questionnaire online. Cases completed anxiety and depression questionnaires (PROMIS-29, GAD-7, PHQ-9). Neonatal data and sociodemographic status were collected. Key Results. We enrolled 79 cases (median age: 27 years old (24;29), sex ratio M/F: 0.4) and 124 controls (median age: 33 years old (27;50), sex ratio M/F: 0.9). Prevalence of functional gastroduodenal disorders and functional bowel disorders were significantly higher in women in the case group (respectively p=0.017 and p=0.015). There was also a higher probability of having one functional bowel disorder (p=0.015) and functional constipation (p=0.02) than in the female control group. Some of the risk factors are directly linked to prematurity (chorioamnionitis, intraventricular hemorrhage) or linked to a consequence of prematurity (anxiety, depression and social abilities). Conclusion. This is the first prospective controlled study reporting the prevalence of DGBI in a cohort of well-characterized adult-born premature. We confirm that prematurity is a risk factor for developing a DGBI.

HNF4[alpha] est un facteur de transcription de la famille des récepteurs nucléaires hormonaux dont le rôle dans l'organogenèse et le maintien des fonctions hépatiques est de mieux en mieux décrit. Cependant, son rôle dans le développement et le maintien des fonctions gastrointestinales est peu connu. Il en va de même pour le facteur de transcription CUX1 au sein de de la muqueuse intestinale. Nous avons ainsi décidé d'utiliser l'invalidation conditionnelle d' HNF4[alpha] (HNF4[alpha] [exposant]fx/fx) dans l'épithélium intestinal grâce à l'expression de la Cre-recombinase sous le contrôle du promoteur de 12.4 kb de la Villine (12.4kb-Villin .Cre). Les épithélia de l'intestin grêle et du côlon ont été étudiés au niveau de leur morphologie, de leur prolifération, de leur différenciation et de leur fonction à différents temps du développement de la souris. Nous avons dans un premier temps constaté que la morphogenèse de ces tissus se déroule normalement. Nous avons cependant observé que l'épithélium de l'intestin grêle présentait une légère augmentation de la prolifération et une modification des populations différenciées au profit des cellules entéroendocrines et caliciformes. Nous avons également identifié une réduction de la conductance de l'épithélium colique du à une dérégulation des canaux, transporteurs et pores impliqués dans la régulation du transport ionique. Des cibles directes d'HNF4[alpha], tel que la claudine-15, ont vu leur expression diminuer chez les animaux mutants ainsi que dans les maladies inflammatoires intestinales durant lesquelles HNF4[alpha] est réduit en expression. Cette modification dans le rôle crucial de la réabsorption des fluides auquel l'épithélium colique participe a eu pour effet d'entrainer une colite spontanée ressemblant à la colite ulcéreuse chez l'humain. En effet, une augmentation de l'inflammation, une augmentation du recrutement de leucocytes, une augmentation de la prolifération et une apparition de dysplasie épithéliale ont été observées. Les épithélia du grêle et du côlon ont également présenté une augmentation du stress oxydatif et de l'apoptose qui s'est avérée être protectrice contre la perte d'hétérozygocité de l'allèle Apc dans le modèle murin de tumorigenèse Apc Min/+ . En effet, les animaux pour lesquels l'invalidation de l'expression d'HNF4[alpha] a été effectuée par la Villine-Cre (Apc[exposant Min/+] HNF4[alpha] [exposant [delta]1EC] ), ont montré une réduction de 70% du nombre de polypes dans l'intestin grêle et une réduction de 90% du nombre de polypes dans le côlon. L'analyse des gènes impliqués dans la réduction des espèces réactives de l'oxygène a permis d'identifier la GSTK1 comme une nouvelle cible directe d'HNF4[alpha] tant dans l'épithélium de l'intestin grêle que dans le cancer colorectal. En effet, l'expression d'HNF4[alpha] chez les patients atteints du cancer colorectal s'est avérée augmentée chez 31 patients sur les 40 analysés. Ces augmentations oscillent entre 50 et 100% chez 22% des patients et de 100% et plus chez 40% des patients analysés ( n = 40). Les animaux Cux1[delta]HD ont quant à eux été étudiés au niveau de leur susceptibilité à un stress inflammatoire. Nous avons démontré que l'expression de CUX1 est nécessaire à la protection de l'inflammation aigüe et chronique et que les patients atteints des maladies inflammatoires intestinales répondent en augmentant l'expression de ce facteur. Nous croyons que l'expression de CUX1 permet de tempérer la réponse inflammatoire et permet aussi la migration et la prolifération de l'épithélium colique en réponse aux blessures causées par l'inflammation soutenue. Collectivement, ces études démontrent l'importance du réseau de régulation transcriptionnelle dans les voies gastrointestinales pour le maintien de l'homéostasie proliférative, fonctionnelle et inflammatoire de l'épithélium. La modulation de ces facteurs durant les pathologies suggère la possibilité d'intervenir thérapeutiquement sur ces facteurs afin de contrôler leurs cibles et ainsi contrer l'apparition, la progression ou la chronicité de ces maladies.

Das Reizdarmsyndrom (RDS) ist eine funktionale Darmerkrankung mit einer Prävalenz von 10.000 – 20.000/100.000 in verschiedenen Kulturen. Keine einzelne physiologische oder psychologische Ursache konnte bisher isoliert werden. Ein sensitiver und spezifischer Maker sind herabgesetzte rektale Schmerzschwellen. Veränderungen der cerebralen viszerosensorischen und nozizeptiven Repräsentation sind mit Neuroimaging-Studien untersucht worden. Die Verarbeitung von Reizen unterhalb der Wahrnehmungsschwelle scheint sich von der Verarbeitung bewusster Reize zu unterscheiden. Wir untersuchten daher sub- und supraliminale rektale Wahrnehmung von 8 RDS-Patienten und 8 parallelisierten gesunden Kontrollprobanden. Die Reizschwelle wurde mit Hilfe eines Tracking-Paradigmas bestimmt. In einer funktionellen Magnetresonanztomographie (fMRT)-Studie wurden Reize unter, über und in der Nähe der Wahrnehmungsschwelle in einem pseudorandomisierten Blockdesign präsentiert. Bei supraliminaler Stimulation gesunder Probanden konnten der bekannte spinothalamische und vagale Pfad repliziert werden. Bei subliminaler Stimulation zeigte sich in einer Einzelauswertung eine ähnliche Verarbeitung, damit konnten die Vorergebnisse hier ebenfalls repliziert werden. In der Gruppenauswertung fand sich Aktivierung nur in Arealen, die bei supraliminaler Stimulation nicht aktiv waren. RDS-Patienten zeigten weniger Aktivität bei subliminaler und mehr bei liminaler Stimulation. Bei supraliminaler Stimulation zeigten sich unterschiedliche aktivierte Areale. Insbesondere war der Amygdala-Hippocampus-Komplex bei Patienten stärker aktiviert. Die Ergebnisse bei supraliminaler und liminaler Stimulation können als verstärkte Aufmerksamkeit auf eben wahrnehmbare Darmreize und als verstärkte emotionale Verarbeitung interpretiert werden. Bei der subliminalen Stimulation kann man schwächere Aktivität schmerzunterdrückender Netze annehmen oder von einem methodischen Artefakt ausgehen. / Irritable bowel syndrome (IBS) is a functional bowel disease with a prevalence of 10.000 - 20.000/100.000 across cultures. So far, no single physiological or psychological reason has been identified. Nevertheless, reduced rectal pain thresholds represent a sensitive and specific marker. Alterations in cerebral viscerosensory and nociceptive representation have been addressed using neuroimaging studies. Processing of stimuli below conscious perception level seems to differ from consciously perceived stimuli. Thus, we examined sub- and supraliminal rectal perception in 8 patients with IBS and 8 healthy matched control subjects. Perception thresholds were assessed by a tracking paradigm. In an functional magnetic resonance imaging (fMRI) study using a block design, stimuli below, above, or around the subjective perception threshold were presented in pseudo-randomized order. At supraliminal stimulation in healthy controls, results of previous studies were replicated and confirmed a spinothalamic and a vagal pathway of visceral sensory perception and suggested processing in amygdala and hippocampus. At subliminal stimulation in healthy controls, previous results were also replicated showing similar processing in single subject analysis. Results of a group analysis yielded only activity in areas not activated at supraliminal stimulation. IBS patients showed less pronounced activity during subliminal stimulation and much more pronounced activity at liminal stimulation. At supraliminal stimulation, different areas showed active in both groups. In particular, the amygdala-hippocampus complex was more active in patients. Results at liminal and supraliminal stimulation can be interpreted as enhanced attention to around-threshold rectal stimuli and more pronounced emotional processing of conciously perceived stimuli. Results at subliminal stimulation can be understood as weaker activity of perception-suppressing pathways or as methodological artifact.

The occupational exposures of sewage workers are complex and variable, and include a great variety of biological and chemical agents. Previous research has focused mostly on infections and various symptoms among sewage workers, e.g. abdominal and respiratory symptoms. At several sewage plants in Sweden, concern arose about occupational cancer, specifically cancer of the stomach, the kidney, and the lung. The aim of this study was to study the cancer incidence among municipal sewage workers, some exposures that might be connected with cancer risk, and self reported abdominal and respiratory symptoms. In a cohort of municipal sewage workers there was no increase in the overall incidence of cancer when compared with the general population. However, there was a slight increase in the incidence of prostate cancer, but not in the sites of original concern among the workers. Infection by the gastric carcinogen Helicobacter pylori (determined from the presence of IgG antibodies in serum against H pylori) was no more prevalent in sewage workers than in comparable referents. Neither were sewage workers more exposed to genotoxic agents than comparable referents, as measured by the alkaline single cell gel electrophoresis (SCG) assay performed on peripheral lymphocytes. There was no increase in the three-month prevalence of abdominal symptoms when compared with other municipal workers. Specifically, there was no difference in prevalence of the common disorders dyspepsia and irritable bowel syndrome. Sewage workers reported adult bronchial asthma significantly more than the referents.