The First 1 1/2 Years of TOTEM Roman Pot Operation at LHC

Since the LHC running season 2010, the TOTEM Roman Pots (RPs) are fully operational and serve for collecting elastic and diffractive proton-proton scattering data. Like for other moveable devices approaching the high intensity LHC beams, a reliable and precise control of the RP position is critical to machine protection. After a review of the RP movement control and position interlock system, the crucial task of alignment will be discussed.Comment: 3 pages, 6 figures; 2nd International Particle Accelerator Conference (IPAC 2011), San Sebastian, Spain; contribution MOPO01

The UK prevalence of hereditary haemorrhagic telangiectasia and its association with sex, socioeconomic status and region of residence: a population-based study

Background Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder of aberrant blood vessel development characterised by arteriovenous malformations. HHT is associated with significant morbidity due to complications including epistaxis, gastrointestinal bleeding and stroke. We explored the hypothesis that a diagnosis of HHT is associated with sex, socioeconomic status and geographical location.Methods We used The Health Improvement Network, a longitudinal, computerised general practice database covering 5% of the UK population to calculate prevalence estimates for HHT stratified by age, sex, socioeconomic status and geographical location.Results The 2010 UK point prevalence for HHT was 1.06/10 000 person years (95% CI 0.95 to 1.17) or 1 in 9400 individuals. The diagnosed prevalence of HHT was significantly higher in women compared with men (adjusted prevalence rate ratio (PRR) 1.53, 95% CI 1.24 to 1.88) and in those from the most affluent socioeconomic group compared with the least (adjusted PRR 1.74, 95% CI 1.14 to 2.64). The PRR varied between different regions of the UK, being highest in the South West and lowest in the West Midlands (adjusted PRR for former compared with latter 1.86, 95% CI 1.61 to 2.15).Conclusions HHT prevalence is more common in the UK population than previously demonstrated, though this updated figure is still likely to be an underestimate. HHT appears to be significantly under-diagnosed in men, which is likely to reflect their lower rates of consultation with primary care services. There is under-diagnosis in patients from lower socioeconomic groups and a marked variation in the prevalence of diagnosis between different geographical regions across the UK that requires further investigation

The perplexity of targeting genetic alterations in hepatocellular carcinoma

Genetic heterogeneity is a well-recognized feature of hepatocellular carcinoma (HCC). The coexistence of multiple genetic alterations in the same HCC nodule contributes to explain why gene-targeted therapy has largely failed. Targeting of early genetic alterations could theoretically be a more effective therapeutic strategy preventing HCC. However, the failure of most targeted therapies has raised much perplexity regarding the role of genetic alterations in driving cancer as the main paradigm. Here, we discuss the methodological and conceptual limitations of targeting genetic alterations and their products that may explain the limited success of the novel mechanism-based drugs in the treatment of HCC. In light of these limitations and despite the era of the so-called “precision medicine,” prevention and early diagnosis of conditions predisposing to HCC remain the gold standard approach to prevent the development of this type of cancer. Finally, a paradigm shift to a more systemic approach to cancer is required to find optimal therapeutic solutions to treat this disease

Dynamic identification of a strategic building of the sixties with a mixed structure

The present paper shows and discusses the results of the identification procedure applied to the building of the Municipality of Castellaneta, Taranto (Puglia, Italy). The case study has been chosen for its structural complexity; indeed, the building has been built in two successive phases, block A built between 1955 and 1957, and block B, for completion, presumably built between the years 1960 and 1961. Block A constitutes the main building and represents the original nucleus. The structure was subsequently subject to structural interventions to replace some load-bearing walls with steel beams. The building constituting block B, joined to the original body of the building, has a structure in load-bearing masonry, while the floors, more recently built, are also in brick-concrete, but with pre-cast prestressed joists. The dynamic response of the building was assessed through OMA (Operational Modal Analysis) identification technique which allows you to determine the properties of the structure in real operating conditions, without the need to interrupt the activities inside the structure itself. The structural excitement, therefore, is due only to the environmental condition. A 3D model was defined in PRO_SAP; the results obtained from the finite element model were subsequently compared with those obtained from the experimental model

Statistics of wind-induced vibrations for a flexible roof

The wind-induced vibration of flexible structures is an important topic in the field of wind engineering in terms of human comfort and safety and of global instability of cable structures. In particular, cable structures used for roofs, for example, cable net and membrane tensile structures, are very sensitive to wind-induced vibrations because the axial force in a cable depends on its geometry. When the cable changes its geometry during the vibrations, it may either lose its tension or the cable tension may exceed the cable's material strength. The wind-structure interaction on flexible roofs is most frequently investigated through numerical analyses using forces time-histories calculated by aerodynamic tests on rigid models. However, this approach fails to predict the effective dynamic deformation of the roof. This paper discusses results obtained from aeroelastic tests in a wind tunnel on flexible roofs. Signals were divided into slots and the statistics of peaks were estimated and discussed through the cumulative distribution function plot. Quantiles of 79%, 93% and 95% of the wind-induced acceleration were compared with the values provided in literature, codes and standards. The comparison showed that the values of accelerations provided in the literature are underestimated

Single-neuron dynamics in human focal epilepsy

Epileptic seizures are traditionally characterized as the ultimate expression of monolithic, hypersynchronous neuronal activity arising from unbalanced runaway excitation. Here we report the first examination of spike train patterns in large ensembles of single neurons during seizures in persons with epilepsy. Contrary to the traditional view, neuronal spiking activity during seizure initiation and spread was highly heterogeneous, not hypersynchronous, suggesting complex interactions among different neuronal groups even at the spatial scale of small cortical patches. In contrast to earlier stages, seizure termination is a nearly homogenous phenomenon followed by an almost complete cessation of spiking across recorded neuronal ensembles. Notably, even neurons outside the region of seizure onset showed significant changes in activity minutes before the seizure. These findings suggest a revision of current thinking about seizure mechanisms and point to the possibility of seizure prevention based on spiking activity in neocortical neurons

Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism

The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a 'real-life setting'. Forty-three obese, diabetic and hypogonadal men (aged 45-59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000-3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol/mol)] and a significant reduction in body weight (p < 0.01), but also a further increase in SHBG (p < 0.05) and T (p < 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p < 0.05) and weight (p < 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED

Pathophysiology of musculoskeletal pain: a narrative review

Musculoskeletal pain (excluding bone cancer pain) affects more than 30% of the global population and imposes an enormous burden on patients, families, and caregivers related to functional limitation, emotional distress, effects on mood, loss of independence, and reduced quality of life. The pathogenic mechanisms of musculoskeletal pain relate to the differential sensory innervation of bones, joints, and muscles as opposed to skin and involve a number of peripheral and central nervous system cells and mediators. The interplay of neurons and non-neural cells (e.g. glial, mesenchymal, and immune cells) amplifies and sensitizes pain signals in a manner that leads to cortical remodeling. Moreover, sex, age, mood, and social factors, together with beliefs, thoughts, and pain behaviors influence the way in which musculoskeletal pain manifests and is understood and assessed. The aim of this narrative review is to summarize the different pathogenic mechanisms underlying musculoskeletal pain and how these mechanisms interact to promote the transition from acute to chronic pain

Assessing extraction methods and mechanical and physicochemical properties of Algerian yucca fibers for sustainable composite reinforcement

The utilization of biofiber in recent years has significantly increased due to its advantages like being environmentally friendly, availability, and low costs. This paper investigates the physicochemical, mechanical, and morphological properties of the yucca fiber extracted by three methods such as water-retting, traditional, and chemical methods. These analyses are designed to evaluate the extraction methodology and the hypothesis of the influence of harvesting location and growth conditions of the fiber. Various technologies are used, such as SEM, FTIR, XRD, and tensile tests. The fiber extracted by water retting is the strongest in the mechanical analysis with a strength of 690.48 MPa, followed by fiber extracted with the traditional method with 685.48 MPa, also 673.06, 657.94, 373.68 MPa for the fiber extracted by the chemical method using 3%, 5%, 10%NaOH respectively. The fiber obtained by the water retting method also has a higher chemical composition with 80.25% cellulose, 10.45% lignin, and 13.75% hemicellulose. The morphological characteristics are examined using Scanning Electron Microscopy. The crystallinity index ranged from 61.75% to 70.77%, and crystallite size from 1.73 to 2.04 nm is calculated from the XRD analysis. All these results confirm that yucca fiber can be a good sustainable choice for composite reinforcement

Apolipoprotein E (APOE) polymorphism influences serum APOE levels in Alzheimer's disease patients and centenarians.

Vascular factors may play a role in the etiology of Alzheimer’s disease (AD) and increased serum apolipoprotein E (APOE) levels in AD could be of interest, as APOE concentration is associated with vascular disease. Aims of this study were to evaluate the inluence of APOE genotype on serum APOE levels, and, secondly, to study serum APOE concentrations in relation to age and AD. APOE genotypes, serum total cholesterol, LDL cholesterol, HDL cholesterol, total cholesterol/HDL cholesterol ratio, triglycerides, and serum APOE were performed on 52 healthy centenarians, 49 AD patients, 45 age-matched controls, and 72 young healthy adults. In all study population a significant trend in reduction of serum APOE levels from APOE E2- to E4 carriers was observed.The diffeerence in serumAPOE levels amonga ge groups signi¢cantly decreased in E4 carriers only, includingH DL cholesterol; no significant differences between AD patients and age-matched controls were found. In these highly selected populations, APOE genotype distribution strongly influences serum APOE concentration, not suggesting, at present, a possible role as a biochemical marker for AD, but only as a putative longevity factor