71 resultados para cross reaction


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The ever expanding growth of the wireless access to the Internet in recent years has led to the proliferation of wireless and mobile devices to connect to the Internet. This has created the possibility of mobile devices equipped with multiple radio interfaces to connect to the Internet using any of several wireless access network technologies such as GPRS, WLAN and WiMAX in order to get the connectivity best suited for the application. These access networks are highly heterogeneous and they vary widely in their characteristics such as bandwidth, propagation delay and geographical coverage. The mechanism by which a mobile device switches between these access networks during an ongoing connection is referred to as vertical handoff and it often results in an abrupt and significant change in the access link characteristics. The most common Internet applications such as Web browsing and e-mail make use of the Transmission Control Protocol (TCP) as their transport protocol and the behaviour of TCP depends on the end-to-end path characteristics such as bandwidth and round-trip time (RTT). As the wireless access link is most likely the bottleneck of a TCP end-to-end path, the abrupt changes in the link characteristics due to a vertical handoff may affect TCP behaviour adversely degrading the performance of the application. The focus of this thesis is to study the effect of a vertical handoff on TCP behaviour and to propose algorithms that improve the handoff behaviour of TCP using cross-layer information about the changes in the access link characteristics. We begin this study by identifying the various problems of TCP due to a vertical handoff based on extensive simulation experiments. We use this study as a basis to develop cross-layer assisted TCP algorithms in handoff scenarios involving GPRS and WLAN access networks. We then extend the scope of the study by developing cross-layer assisted TCP algorithms in a broader context applicable to a wide range of bandwidth and delay changes during a handoff. And finally, the algorithms developed here are shown to be easily extendable to the multiple-TCP flow scenario. We evaluate the proposed algorithms by comparison with standard TCP (TCP SACK) and show that the proposed algorithms are effective in improving TCP behavior in vertical handoff involving a wide range of bandwidth and delay of the access networks. Our algorithms are easy to implement in real systems and they involve modifications to the TCP sender algorithm only. The proposed algorithms are conservative in nature and they do not adversely affect the performance of TCP in the absence of cross-layer information.

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Microneurovascular free muscle transfer with cross-over nerve grafts in facial reanimation Loss of facial symmetry and mimetic function as seen in facial paralysis has an enormous impact on the psychosocial conditions of the patients. Patients with severe long-term facial paralysis are often reanimated with a two-stage procedure combining cross-facial nerve grafting, and 6 to 8 months later with microneurovascular (MNV) muscle transfer. In this thesis, we recorded the long-term results of MNV surgery in facial paralysis and observed the possible contributing factors to final functional and aesthetic outcome after this procedure. Twenty-seven out of forty patients operated on were interviewed, and the functional outcome was graded. Magnetic resonance imaging (MRI) of MNV muscle flaps was done, and nerve graft samples (n=37) were obtained in second stage of the operation and muscle biopsies (n=18) were taken during secondary operations.. The structure of MNV muscles and nerve grafts was evaluated using histological and immunohistochemical methods ( Ki-67, anti-myosin fast, S-100, NF-200, CD-31, p75NGFR, VEGF, Flt-1, Flk-1). Statistical analysis was performed. In our studies, we found that almost two-thirds of the patients achieved good result in facial reanimation. The longer the follow-up time after muscle transfer the weaker was the muscle function. A majority of the patients (78%) defined their quality of life improved after surgery. In MRI study, the free MNV flaps were significantly smaller than originally. A correlation was found between good functional outcome and normal muscle structure in MRI. In muscle biopsies, the mean muscle fiber diameter was diminished to 40% compared to control values. Proliferative activity of satellite cells was seen in 60% of the samples and it tended to decline with an increase of follow-up time. All samples showed intramuscular innervation. Severe muscle atrophy correlated with prolonged intraoperative ischaemia. The good long-term functional outcome correlated with dominance of fast fibers in muscle grafts. In nerve grafts, the mean number of viable axons amounted to 38% of that in control samples. The grafted nerves characterized by fibrosis and regenerated axons were thinner than in control samples although they were well vascularized. A longer time between cross facial nerve grafting and biopsy sampling correlated with a higher number of viable axons. P75Nerve Growth Factor Receptor (p75NGFR) was expressed in every nerve graft sample. The expression of p75NGFR was lower in older than in younger patients. A high expression of p75NGFR was often seen with better function of the transplanted muscle. In grafted nerve Vascular Endothelial Growth Factor (VEGF) and its receptors were expressed in nervous tissue. In conclusion, most of the patients achieved good result in facial reanimation and were satisfied with the functional outcome. The mimic function was poorer in patients with longer follow-up time. MRI can be used to evaluate the structure of the microneurovascular muscle flaps. Regeneration of the muscle flaps was still going on many years after the transplantation and reinnervation was seen in all muscle samples. Grafted nerves were characterized by fibrosis and fewer, thinner axons compared to control nerves although they were well vascularized. P75NGFR and VEGF were expressed in human nerve grafts with higher intensity than in control nerves which is described for the first time.

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The aims of this study were to describe Finnish day surgery practice at present and to evaluate quality of care by assessing postdischarge minor morbidity and quality indicators. Potential treatment options were approached by investigating the role of oral dexamethasone as a part of multimodal analgesia and the feasibility of day surgery in patients aged 65 years and older. Over a 2-month period, all patient cases at 14 Finnish day surgery or short-stay units were analyzed (Study I). Quality indicators included rates and reasons for overnight admission, readmission, reoperation, cancellations, and patient satisfaction. Recovery during the first postoperative week was assessed at two units (Study II). Altogether 2732 patients graded daily the intensity of predefined symptoms. To define risk factors of postdischarge symptoms, multinomial regression analysis was used. Sixty patients scheduled to undergo day surgery for hallux valgus were randomized to receive twice perioperatively dexamethasone 9 mg or placebo (Study III). Paracetamol 1 g was administered 3 times daily. Rescue medication (oxycodone) consumption during 0-3 postoperative days (POD), maximal pain scores and adverse effects were documented. Medically stable patients aged 65 years or older, scheduled for open inguinal hernia repair, were randomized to receive treatment either as day cases or inpatients (Study IV). Complications, unplanned admissions, healthcare visits, and patients’ acceptance of the type of care provided were assessed during 2 weeks postoperatively. In Study I, unplanned overnight admissions were reported in 5.9%, return hospital visits during PODs 1-28 in 3.7%, and readmissions in 0.7% of patients. Patient satisfaction was high. In Study II, pain was the most common symptom in adult patients (57%). Postdischarge symptoms were more frequent in adults aged < 40 years, children aged ≥ 7 years, females, and following a longer duration of surgery. In Study III, the total median (range) oxycodone consumption during the study period was 45 (0–165) mg in the dexamethasone group, compared with 78 (15–175) mg in the placebo group (P < 0.049). On PODs 0-1, patients in the dexamethasone group reported significantly lower pain scores. Following inguinal hernia repair, no significant differences in outcome measures were seen between the study groups. Patient satisfaction was equally high in day cases and inpatients (Study IV). Finnish day surgery units provide good-quality services. Minor postdischarge symptoms are common, and they are influenced by several patient-, surgery-, and anesthesia-related factors. Oral dexamethasone combined with paracetamol improves pain relief and reduces the need for oxycodone rescue medication following correction of hallux valgus. Day surgery for open inguinal hernia repair is safe and well accepted by patients aged 65 years or older and can be recommended as the primary choice of care for medically stable patients.

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Atherosclerosis is an inflammatory disease characterized by accumulation of lipids in the inner layer of the arterial wall. During atherogenesis, various structures that are recognized as non-self by the immune system, such as modified lipoproteins, are deposited in the arterial wall. Accordingly, atherosclerotic lesions and blood of humans and animals with atherosclerotic lesions show signs of activation of both innate and adaptive immune responses. Although immune attack is initially a self-protective reaction, which is meant to destroy or remove harmful agents, a chronic inflammatory state in the arterial wall accelerates atherosclerosis. Indeed, various modulations of the immune system of atherosclerosis-prone animals have provided us with convincing evidence that immunological mechanisms play an important role in the pathogenesis of atherosclerosis. This thesis focuses on the role of complement system, a player of the innate immunity, in atherosclerosis. Complement activation via any of the three different pathways (classical, alternative, lectin) proceeds as a self-amplifying cascade, which leads to the generation of opsonins, anaphylatoxins C3a and C5a, and terminal membrane-attack complex (MAC, C5b-9), all of which regulate the inflammatory response and act in concert to destroy their target structures. To prevent uncontrolled complement activation or its attack against normal host cells, complement needs to be under strict control by regulatory proteins. The complement system has been shown to be activated in atherosclerotic lesions, modified lipoproteins and immune complexes containing oxLDL, for instance, being its activators. First, we investigated the presence and role of complement regulators in human atherosclerotic lesions. We found that inhibitors of the classical and alternative pathways, C4b-binding protein and factor H, respectively, were present in atherosclerotic lesions, where they localized in the superficial proteoglycan-rich layer. In addition, both inhibitors were found to bind to arterial proteoglycans in vitro. Immunohistochemical stainings revealed that, in the superficial layer of the intima, complement activation had been limited to the C3 level, whereas in the deeper intimal layers, complement activation had proceeded to the terminal C5b-9 level. We were also able to show that arterial proteoglycans inhibit complement activation in vitro. These findings suggested to us that the proteoglycan-rich layer of the arterial intima contains matrix-bound complement inhibitors and forms a protective zone, in which complement activation is restricted to the C3 level. Thus, complement activation is regulated in atherosclerotic lesions, and the extracellular matrix is involved in this process. Next, we studied whether the receptors for the two complement derived effectors, anaphylatoxins C3a and C5a, are expressed in human coronary atherosclerotic lesions. Our results of immunohistochemistry and RT-PCR analysis showed that, in contrast to normal intima, C3aR and C5aR were highly expressed in atherosclerotic lesions. In atherosclerotic plaques, the principal cells expressing both C3aR and C5aR were macrophages. Moreover, T cells expressed C5aR, and a small fraction of them also expressed C3aR, mast cells expressed C5aR, whereas endothelial cells and subendothelial smooth muscle cells expressed both C3aR and C5aR. These results suggested that intimal cells can respond to and become activated by complement-derived anaphylatoxins. Finally, we wanted to learn, whether oxLDL-IgG immune complexes, activators of the classical complement pathway, could have direct cellular effects in atherogenesis. Thus, we tested whether oxLDL-IgG immune complexes affect the survival of human monocytes, the precursors of macrophages, which are the most abundant inflammatory cell type in atherosclerotic lesions. We found that OxLDL-IgG immune complexes, in addition to transforming monocytes into foam cells, promoted their survival by decreasing their spontaneous apoptosis. This effect was mediated by cross-linking Fc receptors with ensuing activation of Akt-dependent survival signaling. Our finding revealed a novel mechanism by which oxLDL-IgG immune complexes can directly affect the accumulation of monocyte-macrophages in human atherosclerotic lesions and thus play a role in atherogenesis.

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Exposure to water-damaged buildings and the associated health problems have evoked concern and created confusion during the past 20 years. Individuals exposed to moisture problem buildings report adverse health effects such as non-specific respiratory symptoms. Microbes, especially fungi, growing on the damp material have been considered as potential sources of the health problems encountered in these buildings. Fungi and their airborne fungal spores contain allergens and secondary metabolites which may trigger allergic as well as inflammatory types of responses in the eyes and airways. Although epidemiological studies have revealed an association between damp buildings and health problems, no direct cause-and-effect relationship has been established. Further knowledge is needed about the epidemiology and the mechanisms leading to the symptoms associated with exposure to fungi. Two different approaches have been used in this thesis in order to investigate the diverse health effects associated with exposure to moulds. In the first part, sensitization to moulds was evaluated and potential cross-reactivity studied in patients attending a hospital for suspected allergy. In the second part, one typical mould known to be found in water-damaged buildings and to produce toxic secondary metabolites was used to study the airway responses in an experimental model. Exposure studies were performed on both naive and allergen sensitized mice. The first part of the study showed that mould allergy is rare and highly dependent on the atopic status of the examined individual. The prevalence of sensitization was 2.7% to Cladosporium herbarum and 2.8% to Alternaria alternata in patients, the majority of whom were atopic subjects. Some of the patients sensitized to mould suffered from atopic eczema. Frequently the patients were observed to possess specific serum IgE antibodies to a yeast present in the normal skin flora, Pityrosporum ovale. In some of these patients, the IgE binding was partly found to be due to binding to shared glycoproteins in the mould and yeast allergen extracts. The second part of the study revealed that exposure to Stachybotrys chartarum spores induced an airway inflammation in the lungs of mice. The inflammation was characterized by an influx of inflammatory cells, mainly neutrophils and lymphocytes, into the lungs but with almost no differences in airway responses seen between the satratoxin producing and non-satratoxin producing strain. On the other hand, when mice were exposed to S. chartarum and sensitized/challenged with ovalbumin the extent of the inflammation was markedly enhanced. A synergistic increase in the numbers of inflammatory cells was seen in BAL and severe inflammation was observed in the histological lung sections. In conclusion, the results in this thesis imply that exposure to moulds in water damaged buildings may trigger health effects in susceptible individuals. The symptoms can rarely be explained by IgE mediated allergy to moulds. Other non-allergic mechanisms seem to be involved. Stachybotrys chartarum is one of the moulds potentially responsible for health problems. In this thesis, new reaction models for the airway inflammation induced by S. chartarum have been found using experimental approaches. The immunological status played an important role in the airway inflammation, enhancing the effects of mould exposure. The results imply that sensitized individuals may be more susceptible to exposure to moulds than non-sensitized individuals.

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A randomised and population-based screening design with new technologies has been applied to the organised cervical cancer screening programme in Finland. In this experiment the women invited to routine five-yearly screening are individually randomised to be screened with automation-assisted cytology, human papillomavirus (HPV) test or conventional cytology. By using the randomised design, the ultimate aim is to assess and compare the long-term outcomes of the different screening regimens. The primary aim of the current study was to evaluate, based on the material collected during the implementation phase of the Finnish randomised screening experiment, the cross-sectional performance and validity of automation-assisted cytology (Papnet system) and primary HPV DNA testing (Hybrid Capture II assay for 13 oncogenic HPV types) within service screening, in comparison to conventional cytology. The parameters of interest were test positivity rate, histological detection rate, relative sensitivity, relative specificity and positive predictive value. Also, the effect of variation in performance by screening laboratory on age-adjusted cervical cancer incidence was assessed. Based on the cross-sectional results, almost no differences were observed in the performance of conventional and automation-assisted screening. Instead, primary HPV screening found 58% (95% confidence interval 19-109%) more cervical lesions than conventional screening. However, this was mainly due to overrepresentation of mild- and moderate-grade lesions and, thus, is likely to result in overtreatment since a great deal of these lesions would never progress to invasive cancer. Primary screening with an HPV DNA test alone caused substantial loss in specificity in comparison to cytological screening. With the use of cytology triage test, the specificity of HPV screening improved close to the level of conventional cytology. The specificity of primary HPV screening was also increased by increasing the test positivity cutoff from the level recommended for clinical use, but the increase was more modest than the one gained with the use of cytology triage. The performance of the cervical cancer screening programme varied widely between the screening laboratories, but the variation in overall programme effectiveness between respective populations was more marginal from the very beginning of the organised screening activity. Thus, conclusive interpretations on the quality or success of screening should not be based on performance parameters only. In the evaluation of cervical cancer screening the outcome should be selected as closely as possible to the true measure of programme effectiveness, which is the number of invasive cervical cancers and subsequent deaths prevented in the target population. The evaluation of benefits and adverse effects of each new suggested screening technology should be performed before the technology becomes an accepted routine in the existing screening programme. At best, the evaluation is performed randomised, within the population and screening programme in question, which makes the results directly applicable to routine use.

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The objective of these studies was to evaluate possible airway inflammation and remodeling at the bronchial level in cross-country skiers without a prior diagnosis of asthma, and relate the findings to patients with mild chronic asthma and patients with newly diagnosed asthma. We also studied the association of airway inflammatory changes and bronchial hyperresponsivess (BHR), and treatment effects in cross-country skiers and in patients with newly diagnosed asthma. Bronchial biopsies were obtained from the subjects by flexible bronchoscopy, and the inflammatory cells (eosinophils, mast cells, T-lymphocytes, macrophages, and neutrophils) were identified by immunohistochemistry. Tenascin (Tn) immunoreactivity in the bronchial basement membrane (BM) was identified by immunofluorescence staining. Lung function was measured with spirometry, and BHR was assessed by methacholine (skiers) or histamine (asthmatics) challenges. Skiers with BHR and asthma-like symptoms were recruited to a drug-intervention study. Skiers were given treatment (22 weeks) with placebo or budesonide (400 µg bid). Patients with newly diagnosed asthma were given treatment for 16 weeks with placebo, salmeterol (SLM) (50 µg bid), fluticasone propionate (FP) (250 µg bid), or disodium cromoglicate (DSCG) (5 mg qid). Bronchial biopsies were obtained at baseline and at the end of the treatment period. In the skiers a distinct airway inflammation was evident. In their bronchial biopsy specimens, T-lymphocyte, macrophage, and eosinophil counts were, respectively greater by 43-fold (P<0.001), 26-fold (P<0.001, and 2-fold (P<0.001) in skiers, and by 70-fold (p>0.001), 63-fold (P<0.001), and 8-fold (P<0.001) in asthmatic subjects than in controls. In skiers, neutrophil counts were more than 2-fold greater than in asthmatic subjects (P<0.05). Tn expression was higher in skiers than in controls and lower in skiers than in mild asthmatics. No significant changes were seen between skiers with or without BHR in the inflammatory cell counts or Tn expression. Treatment with inhaled budesonide did not attenuate asthma-like symptoms, the inflammatory cell infiltration, or BM Tn expression in the skiers. In newly diagnosed asthmatic patients, SLM, FP, and DSCG reduced asthma symptoms, and need for rescue medication (P<0.04). BHR was reduced by doubling doses 2.78, 5.22, and 1.35 respectively (all P<0.05). SLM and placebo had no effect on cell counts or Tn expression. FP and DSCG reduced eosinophil counts in the bronchial biopsy specimens (P<0.02 and <0.048, respectively). No significant change in tenascin expression appeared in any treatment group. Regarding to atopy, no significant differences existed in the inflammatory cell counts in the bronchial mucosa of subjects with newly diagnosed asthma or in elite cross country skiers. Tn expression in the BM was significantly higher in atopic asthma than in those with nonatopic asthma. Airway inflammation occurred in elite cross-country skiers with and without respiratory symptoms or BHR. Their inflammatory cell pattern differed from that in asthma. Infiltration with eosinophils, macrophages, and mast cells was milder, but lymphocyte counts did not differ from counts in asthmatic airways. Neutrophilic infiltration was more extensive in skiers than in asthmatics. Remodeling took place in the skiers’ airways, as reflected by increased expression of BM tenascin These inflammatory changes and Tn expression may be caused by prolonged exposure of the lower airways to inadequately humidified cold air. In skiers inflammatory changes and remodeling were not reversed with anti-inflammatory treatment. In contrast, in patients with newly diagnosed asthma, anti-inflammatory treatment did attenuate eosinophilic inflammation in the bronchial mucosa. In skiers, anti-inflammatory treatment did not attenuate BHR as it did in asthmatic patients. The BHR in skiers was attenuated spontaneously during placebo treatment, with no difference from budesonide treatment. Lower training intensity during the treatment period may explain this spontaneous decrease in BHR. The origin of BHR probably differs in skiers and in asthmatics. No significant association between BHR and inflammatory cell counts or between BHR and Tn expression was evident in cross-country skiers or asthmatic subjects. Airway remodeling differed between atopic and nonatopic asthma. As opposed to nonatopic asthma, Tn expression was higher in atopic asthma and is related to inflammatory cell densities.

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The study analyses the reaction of urban residents to problems, i.e. disturbing factors, in their living environment, and also their ways of doing something about these problems. It is based on urban-sociological theory on everyday life in a modern metropolis. On this theoretical basis, problems in the urban living environment are analysed in terms of a policy of everyday interference: when urban citizens become aware of a problem in their environment, they face a pattern of behaviour where the norm is polite indifference and negative solidarity. They may feel they ought to do something about the problem, but at the same time, an implicit rule of urban life is not to interfere with other people s lives so they won t interfere with yours. For example, it is not that easy for someone disturbed by littering to complain directly to those who litter the streets. Or if you complain about tobacco smoke from the neighbour s balcony, your neighbours might get cross. Direct interference with a problem in the environment usually implies an encounter with a hitherto unknown counterpart and their possible counter-reaction. The risk is either to lose face or get into downright conflict. Therefore, an easier way may be to complain to the city authorities. The Helsinki City Environment Centre is currently working on solutions for all the various kinds of problems that occur in a dense urban structure. Various ways of conceptualising the problems in the living environment are analysed empirically using theme interviews made with citizens having contacted Helsinki City Environment Centre. A phenomenographic approach and a theory-based categorisation are applied on the analysis of the theme interviews. On the grounds of the analysis, the ways of conceptualising are determined by 1) the difficulty of interfering and convincing other people, which in practice means meddling in other people s business, 2) a territorial struggle for space and a place in a dense urban structure, 3) breaches of rules and norms for social routines in urban life, and 4) a crumbling of the urban identity and all that goes along with that. The analysis of the ways of conceptualisation is deepened using a cultural risk theory. The final outcome of the analysis is four types of behaviour among urban residents with regard to interference with everyday problems in the living environment. They have been called yard police , fence builder , park warden and environmental caretaker . The study combines an urban-sociological approach with the theoretical tradition of urban research and with research on municipal environmental policy.

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We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

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We report a set of measurements of particle production in inelastic pbar{p} collisions collected with a minimum-bias trigger at the Tevatron Collider with the CDF II experiment. The inclusive charged particle transverse momentum differential cross section is measured, with improved precision, over a range about ten times wider than in previous measurements. The former modeling of the spectrum appears to be incompatible with the high particle momenta observed. The dependence of the charged particle transverse momentum on the event particle multiplicity is analyzed to study the various components of hadron interactions. This is one of the observable variables most poorly reproduced by the available Monte Carlo generators. A first measurement of the event transverse energy sum differential cross section is also reported. A comparison with a Pythia prediction at the hadron level is performed. The inclusive charged particle differential production cross section is fairly well reproduced only in the transverse momentum range available from previous measurements. At higher momentum the agreement is poor. The transverse energy sum is poorly reproduced over the whole spectrum. The dependence of the charged particle transverse momentum on the particle multiplicity needs the introduction of more sophisticated particle production mechanisms, such as multiple parton interactions, in order to be better explained.

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At the Tevatron, the total p_bar-p cross-section has been measured by CDF at 546 GeV and 1.8 TeV, and by E710/E811 at 1.8 TeV. The two results at 1.8 TeV disagree by 2.6 standard deviations, introducing big uncertainties into extrapolations to higher energies. At the LHC, the TOTEM collaboration is preparing to resolve the ambiguity by measuring the total p-p cross-section with a precision of about 1 %. Like at the Tevatron experiments, the luminosity-independent method based on the Optical Theorem will be used. The Tevatron experiments have also performed a vast range of studies about soft and hard diffractive events, partly with antiproton tagging by Roman Pots, partly with rapidity gap tagging. At the LHC, the combined CMS/TOTEM experiments will carry out their diffractive programme with an unprecedented rapidity coverage and Roman Pot spectrometers on both sides of the interaction point. The physics menu comprises detailed studies of soft diffractive differential cross-sections, diffractive structure functions, rapidity gap survival and exclusive central production by Double Pomeron Exchange.