High-mass Drell-Yan cross-section and search for new phenomena in multi-electron/positron final states with the ATLAS detector

The Standard Model of particle physics is a very successful theory which describes nearly all known processes of particle physics very precisely. Nevertheless, there are several observations which cannot be explained within the existing theory. In this thesis, two analyses with high energy electrons and positrons using data of the ATLAS detector are presented. One, probing the Standard Model of particle physics and another searching for phenomena beyond the Standard Model.rnThe production of an electron-positron pair via the Drell-Yan process leads to a very clean signature in the detector with low background contributions. This allows for a very precise measurement of the cross-section and can be used as a precision test of perturbative quantum chromodynamics (pQCD) where this process has been calculated at next-to-next-to-leading order (NNLO). The invariant mass spectrum mee is sensitive to parton distribution functions (PFDs), in particular to the poorly known distribution of antiquarks at large momentum fraction (Bjoerken x). The measurementrnof the high-mass Drell-Yan cross-section in proton-proton collisions at a center-of-mass energy of sqrt(s) = 7 TeV is performed on a dataset collected with the ATLAS detector, corresponding to an integrated luminosity of 4.7 fb-1. The differential cross-section of pp -> Z/gamma + X -> e+e- + X is measured as a function of the invariant mass in the range 116 GeV < mee < 1500 GeV. The background is estimated using a data driven method and Monte Carlo simulations. The final cross-section is corrected for detector effects and different levels of final state radiation corrections. A comparison isrnmade to various event generators and to predictions of pQCD calculations at NNLO. A good agreement within the uncertainties between measured cross-sections and Standard Model predictions is observed.rnExamples of observed phenomena which can not be explained by the Standard Model are the amount of dark matter in the universe and neutrino oscillations. To explain these phenomena several extensions of the Standard Model are proposed, some of them leading to new processes with a high multiplicity of electrons and/or positrons in the final state. A model independent search in multi-object final states, with objects defined as electrons and positrons, is performed to search for these phenomenas. Therndataset collected at a center-of-mass energy of sqrt(s) = 8 TeV, corresponding to an integrated luminosity of 20.3 fb-1 is used. The events are separated in different categories using the object multiplicity. The data-driven background method, already used for the cross-section measurement was developed further for up to five objects to get an estimation of the number of events including fake contributions. Within the uncertainties the comparison between data and Standard Model predictions shows no significant deviations.

Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10

Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609?620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.

[Urinary incontinence]

Incontinence is a common age-dependent and increasing problem in women that may mainly present as stress incontinence, overactive bladder, mixed incontinence or other forms. A thorough history, gynaecological and neurological examination and urinalysis as initial step will lead to the diagnosis and treatment. If midstream urine is difficult to receive, a catheter urine will be easy to obtain. Further investigations as urodynamics, cystoscopy and ultrasound may be required. As initial step, stress incontinence should be treated with physiotherapy and pelvic floor exercises, if not successful with operations as suburethral slings. Slings have good long-term success rates of approximately 85 % with a low morbidity and can even be inserted under local anaesthetic. The treatment of idiopathic overactive bladder consists of bladder training, a behavioural therapy, and mainly anticholinergics. Anticholinergics may cause side effects particularly in the elderly who are under several medications that may add anticholinergic effects as antidepressants, antibiotics or antihistaminics.

Melody recognition at fast and slow tempos: Effects of age, experience, and familiarity

Eighty-one listeners defined by three age ranges (18–30, 31–59, and over 60 years) and three levels of musical experience performed an immediate recognition task requiring the detection of alterations in melodies. On each trial, a brief melody was presented, followed 5 sec later by a test stimulus that either was identical to the target or had two pitches changed, for a same–different judgment. Each melody pair was presented at 0.6 note/sec, 3.0 notes/sec, or 6.0 notes/sec. Performance was better with familiar melodies than with unfamiliar melodies. Overall performance declined slightly with age and improved substantially with increasing experience, in agreement with earlier results in an identification task. Tempo affected performance on familiar tunes (moderate was best), but not on unfamiliar tunes. We discuss these results in terms of theories of dynamic attending, cognitive slowing, and working memory in aging.

[Osteoporosis - whom to treat? The importance of FRAX® in Switzerland]

The WHO fracture risk assessment tool FRAX® is a computer based algorithm that provides models for the assessment of fracture probability in men and women. The approach uses easily obtained clinical risk factors (CRFs) to estimate 10-year probability of a major osteoporotic fracture (hip, clinical spine, humerus or wrist fracture) and the 10-year probability of a hip fracture. The estimate can be used alone or with femoral neck bone mineral density (BMD) to enhance fracture risk prediction. FRAX® is the only risk engine which takes into account the hazard of death as well as that of fracture. Probability of fracture is calculated in men and women from age, body mass index, and dichotomized variables that comprise a prior fragility fracture, parental history of hip fracture, current tobacco smoking, ever long-term use of oral glucocorticoids, rheumatoid arthritis, other causes of secondary osteoporosis, daily alcohol consumption of 3 or more units daily. The relationship between risk factors and fracture probability was constructed using information of nine population-based cohorts from around the world. CRFs for fracture had been identified that provided independent information on fracture risk based on a series of meta-analyses. The FRAX® algorithm was validated in 11 independent cohorts with in excess of 1 million patient-years, including the Swiss SEMOF cohort. Since fracture risk varies markedly in different regions of the world, FRAX® models need to be calibrated to those countries where the epidemiology of fracture and death is known. Models are currently available for 31 countries across the world. The Swiss-specific FRAX® model was developed very soon after the first release of FRAX® in 2008 and was published in 2009, using Swiss epidemiological data, integrating fracture risk and death hazard of our country. Two FRAX®-based approaches may be used to explore intervention thresholds. They have recently been investigated in the Swiss setting. In the first approach the guideline that individuals with a fracture probability equal to or exceeding that of women with a prior fragility fracture should be considered for treatment is translated into thresholds using 10-year fracture probabilities. In that case the threshold is age-dependent and increases from 16 % at the age of 60 ys to 40 % at the age of 80 ys. The second approach is a cost-effectiveness approach. Using a FRAX®-based intervention threshold of 15 % for both, women and men 50 years and older, should permit cost-effective access to therapy to patients at high fracture probability in our country and thereby contribute to further reduce the growing burden of osteoporotic fractures.

Long-term course of lung clearance index between infancy and school-age in cystic fibrosis subjects

Multiple breath washout (MBW) measurements have recently been shown to be sensitive for detection of early cystic fibrosis (CF) lung disease, with the lung clearance index (LCI) being the most common measure for ventilation inhomogeneity. The aim of this observational study was to describe the longitudinal course of LCI from time of clinical diagnosis during infancy to school-age in eleven children with CF. Elevated LCI during infancy was present in seven subjects, especially in those with later clinical diagnosis. Tracking of LCI at follow-up was evident only in the four most severe cases. We provide the first longitudinal data describing the long-term course of LCI in a small group of infants with CF. Our findings support the clinical usefulness of MBW measurements to detect and monitor early lung disease in children with CF already present shortly after clinical diagnosis.

Adsorption behavior of redox-active suppressor additives: Combined electrochemical and STM studies

The redox chemistry and the related surface phase behavior of Safranine (SAF) and Janus Green B (JGB) have been studied by means of cyclic voltammetry in combination with in situ Scanning Tunneling Microscopy using HOPG (Highly Oriented Pyrolytic Graphite) and single crystalline Cu(1 0 0) as model substrates, both revealing different widths of the accessible potential windows. JGB and SAF serve as prototypical heterocyclic suppressor/leveler additives that are used for the metallization of 3D-TSVs (3D Through Silicon Vias) following a classical "leveling" concept. SAF can be considered as the reductive decomposition product of JGB that is formed at the copper/electrolyte interface upon electroplating. Both additives reveal a pronounced pH-dependent redox-chemistry with redox-transitions lying close to or even beyond the anodic limit of the copper potential window. Affected by these redox-processes are in particular the aromatic cores of those heterocycles that can be (quasi)reversibly reduced by a two electron transfer process within the potential window of copper. Therefore we identify the reduced form of those dyes as the active components for the suppressing/leveling effect in copper plating. STM data clearly shows a dye surface phase behavior that is crucially determined by its potential-dependent redox-chemistry. This will be exemplarily discussed for the SAF dye. On chloride-modified Cu(1 0 0) mono-reduced SAF forms a structurally well-defined monolayer of cationic stacking polymers. However, this coupled anion/cation layer reveals only minor suppressing capabilities with respect to the copper dissolution and deposition processes. Complete reduction of the aromatic heterocycle finally leads to the 3D precipitation of hydrophobic reaction products. 3D clusters of this SAF precipitate are discussed as the active structural motif for the suppressing effect of these dyes. (C) 2011 Elsevier Ltd. All rights reserved.

Pediatric and adult eosinophilic esophagitis: similarities and differences

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.

Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS)

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a childhood-onset neurological disease resulting from mutations in the SACS gene encoding sacsin, a 4,579-aa protein of unknown function. Originally identified as a founder disease in Québec, ARSACS is now recognized worldwide. Prominent features include pyramidal spasticity and cerebellar ataxia, but the underlying pathology and pathophysiological mechanisms are unknown. We have generated an animal model for ARSACS, sacsin knockout mice, that display age-dependent neurodegeneration of cerebellar Purkinje cells. To explore the pathophysiological basis for this observation, we examined the cell biological properties of sacsin. We show that sacsin localizes to mitochondria in non-neuronal cells and primary neurons and that it interacts with dynamin-related protein 1, which participates in mitochondrial fission. Fibroblasts from ARSACS patients show a hyperfused mitochondrial network, consistent with defects in mitochondrial fission. Sacsin knockdown leads to an overly interconnected and functionally impaired mitochondrial network, and mitochondria accumulate in the soma and proximal dendrites of sacsin knockdown neurons. Disruption of mitochondrial transport into dendrites has been shown to lead to abnormal dendritic morphology, and we observe striking alterations in the organization of dendritic fields in the cerebellum of knockout mice that precedes Purkinje cell death. Our data identifies mitochondrial dysfunction/mislocalization as the likely cellular basis for ARSACS and indicates a role for sacsin in regulation of mitochondrial dynamics.

Risk attribution of Campylobacter infection by age group using exposure modelling

Knowledge on the relative importance of alternative sources of human campylobacteriosis is important in order to implement effective disease prevention measures. The objective of this study was to assess the relative importance of three key exposure pathways (travelling abroad, poultry meat, pet contact) for different patient age groups in Switzerland. With a stochastic exposure model data on Campylobacter incidence for the years 2002-2007 were linked with data for the three exposure pathways and the results of a case-control study. Mean values for the population attributable fractions (PAF) over all age groups and years were 27% (95% CI 17-39) for poultry consumption, 27% (95% CI 22-32) for travelling abroad, 8% (95% CI 6-9) for pet contact and 39% (95% CI 25-50) for other risk factors. This model provided robust results when using data available for Switzerland, but the uncertainties remained high. The output of the model could be improved if more accurate input data are available to estimate the infection rate per exposure. In particular, the relatively high proportion of cases attributed to 'other risk factors' requires further attention.

Interethnic Interaction Dynamics in the Russian Federation

The collapse of the Soviet Union at the beginning of the 1990s also meant the end of the idea of a common soviet identity incarnated in the "soviet man" and the new "historic community of the soviet people". While this idea still lives on in the generations of the 1920s to 1940s, the younger generations tend to prefer identification with family, profession, ethnic group or religion. Ms. Alexakhina set out to investigate different interethnic interaction strategies in the multi-ethnic context of the Russian Federation, with an emphasis on analysing the role of cultural and ethno-demographic characteristics of minority ethnic groups. It aimed to identify those specific patterns of interaction dynamics that have emerged in response to the political and economic transformation at present under way. The basic supposition was that the size and growth of an ethnic population are defined not only by demographic features such as fertility, mortality and net migration, but are also dependent on processes interethnic interaction and ethnic transition. The central hypothesis of the project was that the multi-ethnic and multi-cultural composition of Russia is apparently manifesting itself in the ethnic minority groups in various forms, but particularly in the form of ethnic revival and/or assimilation. The results of these complex phenomena are manifested as changes in ethnic attachments (national re-identification and language behaviour (multi-lingualism, language transition and loss of the mother tongue). The stress of the political and economic crisis has stimulated significant changes in ethnographic, social and cultural characteristics of inter-ethnic dynamics such as the rate of national re-identification, language behaviour, migration activity and the spread of mixed marriages, among both those minorities with a long history of settlement in Russia and those that were annexed during the soviet period. Patterns of language behaviour and the spread of mixed marriages were taken as the main indicators of the directions of interethnic interaction described as assimilation, ethnic revival and cultural pluralism. The first stage of the research involved a statistical analysis of census data from 1959 to 1994 in order to analyse the changing demographic composition of the largest ethnic groups of the Russian Federation. Until 1989 interethnic interaction in soviet society was distinguished by the process of russification but the political and economic transformation has stimulated the process of ethnic revival, leading to an apparent fall in the size of the Russian population due to ethnic re-identification by members of other ethnic groups who had previously identified themselves as Russian. Cross-classification of nationalities by demographic, social and cultural indicators has shown that the most important determinants of the nature of interethnic interaction are cultural factors such as religion and language affiliation. The analysis of the dynamics of language shift through the study of bilingualism and the domains of language usage for different demographic groups revealed a strong correlation between recognition of Russian as a mother tongue among some non-Russian ethnic groups and the declining size of these groups. The main conclusion from this macro-analysis of census data was the hypothesis of the growing importance of social and political factors upon ethnic succession, that ethnic identity is no longer a stable characteristic but has become dynamic in nature. In order to verify this hypothesis Ms. Alexakhina conducted a survey in four regions showing different patterns of interethnic interaction: the Karelian Republic, Buryatiya, the Nenezkii Autonomous Region and Tatarstan. These represented the west, east, north and south of the Russian Federation. Samples for the survey were prepared on the basis of census lists so as to exclude mono-Russian families in favour of mixed and ethnic-minority families. The survey confirmed the significant growth in the importance of ethnic affiliation in the everyday lives of people in the Federation following the de-centralisation of the political and economic spheres. Language was shown to be a key symbol of the consciousness of national distinction, confirmed by the fact that the process of russification has been reversed by the active mastering of the languages of titular nationalities. The results also confirmed that individual ethnic identity has ceased to be a fixed personal characteristic of one's cultural and genetic belonging, and people's social adaptation to the current political, social and economic conditions is also demonstrated in changes in individual ethnic self-identification. In general terms, the dynamic nature of national identity means that ethnic identity is at present acquiring the special features of overall social identity, for which the frequent change of priorities is an inherent feature of a person's life cycle. These are mainly linked with a multi-ethnic environment and high individual social mobility. From her results Ms. Alexakhina concludes that the development of national languages and multi-lingualism, together with the preservation of Russian as a state language, seems to be the most promising path to peaceful coexistence and the development of the national cultures of different ethnic groups within the Russian Federation.

Effect of Alzheimer caregiving stress and age on frailty markers interleukin-6, C-reactive protein, and D-dimer

BACKGROUND: Elevated plasma levels of interleukin (IL)-6, C-reactive protein (CRP), and D-dimer belong to the biological alterations of the "frailty syndrome," defining increased vulnerability for diseases and mortality with aging. We hypothesized that, compatible with premature frailty, chronic stress and age are related in predicting inflammation and coagulation activity in Alzheimer caregivers. METHODS: Plasma IL-6, CRP, and D-dimer levels were measured in 170 individuals (mean age 73 +/- 9 years; 116 caregivers, 54 noncaregiving controls). Demographic factors, diseases, drugs, and lifestyle variables potentially affecting inflammation and coagulation were obtained by history and adjusted for as covariates in statistical analyses. RESULTS: Caregivers had higher mean levels of IL-6 (1.38 +/- 1.42 vs 1.00 +/- 0.92 pg/mL, p =.032) and of D-dimer (723 +/- 530 vs 471 +/- 211 ng/mL, p <.001) than controls had. CRP levels were similar between groups (p =.44). The relationship between caregiver status and D-dimer was independent of covariates (p =.037) but affected by role overload. Age accounted for much of the relationship with IL-6. After controlling for covariates, the interaction between caregiver status and age was significant for D-dimer (beta =.20, p =.029) and of borderline significance for IL-6 (beta =.17, p =.090). Post hoc regression analyses indicated that, among caregivers, age was significantly correlated with both D-dimer (beta =.50, p <.001) and IL-6 (beta =.38, p =.001). Among controls, however, no significant relationship was observed between age and either D-dimer or IL-6. CONCLUSIONS: The interaction between caregiving status and age for D-dimer and IL-6 suggests the possibility that older caregivers could be at risk of a more rapid transition to the frailty syndrome and clinical manifestations of cardiovascular diseases.

Non-invasive monitoring of renal oxygenation using BOLD-MRI: a reproducibility study

Blood oxygenation level-dependent (BOLD) MRI was shown to allow non-invasive observation of renal oxygenation in humans. However, clinical applications of this type of functional MRI of the kidney are still limited, most likely because of difficulties in obtaining reproducible and reliable information. The aim of this study was to evaluate the reproducibility and robustness of a BOLD method applied to the kidneys and to identify systematic physiological changes potentially influencing the renal oxygenation of healthy volunteers. To measure the BOLD effect, a modified multi-echo data image combination (MEDIC) sequence was used to acquire 12 T2*-weighted images within a single breath-hold. Three identical measurements were performed on three axial and three coronal slices of right and left kidneys in 18 volunteers. The mean R2* (1/T2*) values determined in medulla and cortex showed no significant differences over three repetitions and low intra-subject coefficients of variation (CV) (3 and 4% in medulla and cortex, respectively). The average R2* values were higher in the medulla (16.15 +/- 0.11) than in the cortex (11.69 +/- 0.18) (P < 0.001). Only a minor influence of slice orientation was observed. Mean R2* values were slightly higher (3%) in the left than in the right kidney (P < 0.001). Differences between volunteers were identified (P < 0.001). Part of these differences was attributable to age-dependent R2* values, since these values increased with age when medulla (P < 0.001, r = 0.67) or cortex (P < 0.020, r = 0.42) were considered. Thus, BOLD measurements in the kidney are highly reproducible and robust. The results allow one to identify the known cortico-medullary gradient of oxygenation evidenced by the gradient of R2* values and suggest that medulla is more hypoxic in older than younger individuals. BOLD-MRI is therefore a useful tool to study sequentially and non-invasively regional oxygenation of human kidneys.

Ranibizumab versus verteporfin for neovascular age-related macular degeneration

BACKGROUND: We compared ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration. METHODS: During the first year of this 2-year, multicenter, double-blind study, we randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or monthly sham injections plus active verteporfin therapy. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months. RESULTS: Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%). CONCLUSIONS: Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594 [ClinicalTrials.gov].).

Association of a large lateral extension of the acromion with rotator cuff tears

BACKGROUND: Factors predisposing to tearing of the rotator cuff are poorly understood. We have observed that the acromion of patients with a rotator cuff tear very often appears large on anteroposterior radiographs or during surgery. The purpose of this study was to quantify the lateral extension of the acromion in patients with a full-thickness rotator cuff tear and in patients with an intact rotator cuff. METHODS: The lateral extension of the acromion was assessed on true anteroposterior radiographs made with the arm in neutral rotation. The distance from the glenoid plane to the lateral border of the acromion was divided by the distance from the glenoid plane to the lateral aspect of the humeral head to calculate the acromion index. This index was determined in a group of 102 patients (average age, 65.0 years) with a proven full-thickness rotator cuff tear, in an age and gender-matched group of forty-seven patients (average age, 63.7 years) with osteoarthritis of the shoulder and an intact rotator cuff, and in an age and gender-matched control group of seventy volunteers (average age, 64.4 years) with an intact rotator cuff as demonstrated by ultrasonography. RESULTS: The average acromion index (and standard deviation) was 0.73 +/- 0.06 in the shoulders with a full-thickness tear, 0.60 +/- 0.08 in those with osteoarthritis and an intact rotator cuff, and 0.64 +/- 0.06 in the asymptomatic, normal shoulders with an intact rotator cuff. The difference between the index in the shoulders with a full-thickness supraspinatus tear and the index in those with an intact rotator cuff was highly significant (p < 0.0001). CONCLUSIONS: A large lateral extension of the acromion appears to be associated with full-thickness tearing of the rotator cuff.