Diffraction and Total Cross-Section at the Tevatron and the LHC

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.

Contrast-enhanced ultrasound of abdominal organs in cats

The primary aim of this thesis was the evaluation of the perfusion of normal organs in cats using contrast-enhanced ultrasound (CEUS), to serve as a reference for later clinical studies. Little is known of the use of CEUS in cats, especially regarding its safety and the effects of anesthesia on the procedure, thus, secondary aims here were to validate the quantitative analyzing method, to investigate the biological effects of CEUS on feline kidneys, and to assess the effect of anesthesia on splenic perfusion in cats undergoing CEUS. -- The studies were conducted on healthy, young, purpose-bred cats. CEUS of the liver, left kidney, spleen, pancreas, small intestine, and mesenteric lymph nodes was performed to characterize the normal perfusion of these organs on ten anesthetized, male cats. To validate the quantification method, the effects of placement and size of the region of interest (ROI) on perfusion parameters were investigated using CEUS: Three separate sets of ROIs were placed in the kidney cortex, varying in location, size, or depth. The biological effects of CEUS on feline kidneys were estimated by measuring urinary enzymatic activities, analyzing urinary specific gravity, pH, protein, creatinine, albumin, and sediment, and measuring plasma urea and creatinine concentrations before and after CEUS. Finally, the impact of anesthesia on contrast enhancement of the spleen was investigated by imaging cats with CEUS first awake and later under anesthesia on separate days. -- Typical perfusion patterns were found for each of the studied organs. The liver had a gradual and more heterogeneous perfusion pattern due to its dual blood flow and close proximity to the diaphragm. An obvious and statistically significant difference emerged in the perfusion between the kidney cortex and medulla. Enhancement in the spleen was very heterogeneous at the beginning of imaging, indicating focal dissimilarities in perfusion. No significant differences emerged in the perfusion parameters between the pancreas, small intestine, and mesenteric lymph nodes. -- The ROI placement and size were found to have an influence on the quantitative measurements of CEUS. Increasing the depth or the size of the ROI decreased the peak intensity value significantly, suggesting that where and how the ROI is placed does matter in quantitative analyses. --- A significant increase occurred in the urinary N-acetyl-β-D-glucosaminidase (NAG) to creatinine ratio after CEUS. No changes were noted in the serum biochemistry profile after CEUS, with the exception of a small decrease in blood urea concentration. The magnitude of the rise in the NAG/creatinine ratio was, however, less than the circadian variation reported earlier in healthy cats. Thus, the changes observed in the laboratory values after CEUS of the left kidney did not indicate any detrimental effects in kidneys. Heterogeneity of the spleen was observed to be less and time of first contrast appearance earlier in nonanesthetized cats than in anesthetized ones, suggesting that anesthesia increases heterogeneity of the feline spleen in CEUS. ---- In conclusion, the results suggest that CEUS can be used also in feline veterinary patients as an additional diagnostics aid. The perfusion patterns found in the imaged organs were typical and similar to those seen earlier in other species, with the exception of the heterogeneous perfusion pattern in the cat spleen. Differences in the perfusion between organs corresponded with physiology. Based on the results, estimation of focal perfusion defects of the spleen in cats should be performed with caution and after the disappearance of the initial heterogeneity, especially in anesthetized or sedated cats. Finally, these results indicate that CEUS can be used safely to analyze kidney perfusion also in cats. Future clinical studies are needed to evaluate the full potential of CEUS in feline medicine as a tool for diagnosing lesions in various organ systems.

Combination antiretroviral therapy -associated lipodystrophy : insights into pathogenesis and treatment

Introduction: Combination antiretroviral therapy (cART) has decreased morbidity and mortality of individuals infected with human immunodeficiency virus type 1 (HIV-1). Its use, however, is associated with adverse effects which increase the patients risk of conditions such as diabetes and coronary heart disease. Perhaps the most stigmatizing side effect is lipodystrophy, i.e., the loss of subcutaneous adipose tissue (SAT) in the face, limbs and trunk while fat accumulates intra-abdominally and dorsocervically. The pathogenesis of cART-associated lipodystrophy is obscure. Nucleoside reverse transcriptase inhibitors (NRTI) have been implicated to cause lipoatrophy via mitochondrial toxicity. There is no known effective treatment for cART-associated lipodystrophy during unchanged antiretroviral regimen in humans, but in vitro data have shown uridine to abrogate NRTI-induced toxicity in adipocytes. Aims: To investigate whether i) cART or lipodystrophy associated with its use affect arterial stiffness; ii) lipoatrophic SAT is inflamed compared to non-lipoatrophic SAT; iii) abdominal SAT from patients with compared to those without cART-associated lipoatrophy differs with respect to mitochondrial DNA (mtDNA) content, adipose tissue inflammation and gene expression, and if NRTIs stavudine and zidovudine are associated with different degree of changes; iv) lipoatrophic abdominal SAT differs from preserved dorsocervical SAT with respect to mtDNA content, adipose tissue inflammation and gene expression in patients with cART-associated lipodystrophy and v) whether uridine can revert lipoatrophy and the associated metabolic disturbances in patients on stavudine or zidovudine based cART. Subjects and methods: 64 cART-treated patients with (n=45) and without lipodystrophy/-atrophy (n=19) were compared cross-sectionally. A marker of arterial stiffness, heart rate corrected augmentation index (AgIHR), was measured by pulse wave analysis. Body composition was measured by magnetic resonance imaging and dual-energy X-ray absorptiometry, and liver fat content by proton magnetic resonance spectroscopy. Gene expression and mtDNA content in SAT were assessed by real-time polymerase chain reaction and microarray. Adipose tissue composition and inflammation were assessed by histology and immunohistochemistry. Dorsocervical and abdominal SAT were studied. The efficacy and safety of uridine for the treatment of cART-associated lipoatrophy were evaluated in a randomized, double-blind, placebo-controlled 3-month trial in 20 lipoatrophic cART-treated patients. Results: Duration of antiretroviral treatment and cumulative exposure to NRTIs and protease inhibitors, but not the presence of cART-associated lipodystrophy, predicted AgIHR independent of age and blood pressure. Gene expression of inflammatory markers was increased in SAT of lipodystrophic as compared to non-lipodystrophic patients. Expression of genes involved in adipogenesis, triglyceride synthesis and glucose disposal was lower and of those involved in mitochondrial biogenesis, apoptosis and oxidative stress higher in SAT of patients with than without cART-associated lipoatrophy. Most changes were more pronounced in stavudine-treated than in zidovudine-treated individuals. Lipoatrophic SAT had lower mtDNA than SAT of non-lipoatrophic patients. Expression of inflammatory genes was lower in dorsocervical than in abdominal SAT. Neither depot had characteristics of brown adipose tissue. Despite being spared from lipoatrophy, dorsocervical SAT of lipodystrophic patients had lower mtDNA than the phenotypically similar corresponding depot of non-lipodystrophic patients. The greatest difference in gene expression between dorsocervical and abdominal SAT, irrespective of lipodystrophy status, was in expression of homeobox genes that regulate transcription and regionalization of organs during embryonal development. Uridine increased limb fat and its proportion of total fat, but had no effect on liver fat content and markers of insulin resistance. Conclusions: Long-term cART is associated with increased arterial stiffness and, thus, with higher cardiovascular risk. Lipoatrophic abdominal SAT is characterized by inflammation, apoptosis and mtDNA depletion. As mtDNA is depleted even in non-lipoatrophic dorsocervical SAT, lipoatrophy is unlikely to be caused directly by mtDNA depletion. Preserved dorsocervical SAT of patients with cART-associated lipodystrophy is less inflamed than their lipoatrophic abdominal SAT, and does not resemble brown adipose tissue. The greatest difference in gene expression between dorsocervical and abdominal SAT is in expression of transcriptional regulators, homeobox genes, which might explain the differential susceptibility of these adipose tissue depots to cART-induced toxicity. Uridine is able to increase peripheral SAT in lipoatrophic patients during unchanged cART.