Computational methods for genome screening

Motivation An actual issue of great interest, both under a theoretical and an applicative perspective, is the analysis of biological sequences for disclosing the information that they encode. The development of new technologies for genome sequencing in the last years, opened new fundamental problems since huge amounts of biological data still deserve an interpretation. Indeed, the sequencing is only the first step of the genome annotation process that consists in the assignment of biological information to each sequence. Hence given the large amount of available data, in silico methods became useful and necessary in order to extract relevant information from sequences. The availability of data from Genome Projects gave rise to new strategies for tackling the basic problems of computational biology such as the determination of the tridimensional structures of proteins, their biological function and their reciprocal interactions. Results The aim of this work has been the implementation of predictive methods that allow the extraction of information on the properties of genomes and proteins starting from the nucleotide and aminoacidic sequences, by taking advantage of the information provided by the comparison of the genome sequences from different species. In the first part of the work a comprehensive large scale genome comparison of 599 organisms is described. 2,6 million of sequences coming from 551 prokaryotic and 48 eukaryotic genomes were aligned and clustered on the basis of their sequence identity. This procedure led to the identification of classes of proteins that are peculiar to the different groups of organisms. Moreover the adopted similarity threshold produced clusters that are homogeneous on the structural point of view and that can be used for structural annotation of uncharacterized sequences. The second part of the work focuses on the characterization of thermostable proteins and on the development of tools able to predict the thermostability of a protein starting from its sequence. By means of Principal Component Analysis the codon composition of a non redundant database comprising 116 prokaryotic genomes has been analyzed and it has been showed that a cross genomic approach can allow the extraction of common determinants of thermostability at the genome level, leading to an overall accuracy in discriminating thermophilic coding sequences equal to 95%. This result outperform those obtained in previous studies. Moreover, we investigated the effect of multiple mutations on protein thermostability. This issue is of great importance in the field of protein engineering, since thermostable proteins are generally more suitable than their mesostable counterparts in technological applications. A Support Vector Machine based method has been trained to predict if a set of mutations can enhance the thermostability of a given protein sequence. The developed predictor achieves 88% accuracy.

Computer-Simulationen zur Strukturbildung von einzelnen Polymerketten

In dieser Arbeit wurden die Phasenübergänge einer einzelnen Polymerkette mit Hilfe der Monte Carlo Methode untersucht. Das Bondfluktuationsmodell wurde zur Simulation benutzt, wobei ein attraktives Kastenpotential zwischen allen Monomeren der Polymerkette gewirkt hat. Drei Arten von Bewegungen sind eingeführt worden, um die Polymerkette richtig zu relaxieren. Diese sind die Hüpfbewegung, die Reptationsbewegung und die Pivotbewegung. Um die Volumenausschlußwechselwirkung zu prüfen und um die Anzahl der Nachbarn jedes Monomers zu bestimmen ist ein hierarchischer Suchalgorithmus eingeführt worden. Die Zustandsdichte des Modells ist mittels des Wang-Landau Algorithmus bestimmt worden. Damit sind thermodynamische Größen berechnet worden, um die Phasenübergänge der einzelnen Polymerkette zu studieren. Wir haben zuerst eine freie Polymerkette untersucht. Der Knäuel-Kügelchen Übergang zeigt sich als ein kontinuierlicher Übergang, bei dem der Knäuel zum Kügelchen zusammenfällt. Der Kügelchen-Kügelchen Übergang bei niedrigeren Temperaturen ist ein Phasenübergang der ersten Ordnung, mit einer Koexistenz des flüssigen und festen Kügelchens, das eine kristalline Struktur hat. Im thermodynamischen Limes sind die Übergangstemperaturen identisch. Das entspricht einem Verschwinden der flüssigen Phase. In zwei Dimensionen zeigt das Modell einen kontinuierlichen Knäuel-Kügelchen Übergang mit einer lokal geordneten Struktur. Wir haben ferner einen Polymermushroom, das ist eine verankerte Polymerkette, zwischen zwei repulsiven Wänden im Abstand D untersucht. Das Phasenverhalten der Polymerkette zeigt einen dimensionalen crossover. Sowohl die Verankerung als auch die Beschränkung fördern den Knäuel-Kügelchen Übergang, wobei es eine Symmetriebrechung gibt, da die Ausdehnung der Polymerkette parallel zu den Wänden schneller schrumpft als die senkrecht zu den Wänden. Die Beschränkung hindert den Kügelchen-Kügelchen Übergang, wobei die Verankerung keinen Einfluss zu haben scheint. Die Übergangstemperaturen im thermodynamischen Limes sind wiederum identisch im Rahmen des Fehlers. Die spezifische Wärme des gleichen Modells aber mit einem abstoßendem Kastenpotential zeigt eine Schottky Anomalie, typisch für ein Zwei-Niveau System.

Are there risk factors for snowboard injuries? A case-control multicentre study of 559 snowboarders

To analyse risk factors leading to injuries during snowboarding.

Mesh shrinkage and pain in laparoscopic ventral hernia repair: a randomized clinical trial comparing suture versus tack mesh fixation

Mesh fixation during laparoscopic ventral hernia repair can be performed using transfascial sutures or metal tacks. The aim of the present study is to compare mesh shrinkage and pain between two different techniques of mesh fixation in a prospective randomized trial.

Can imagined whole-body rotations improve vestibular compensation?

Unilateral damage to the labyrinth and the vestibular nerve cause rotational vertigo, postural imbalance, oculomotor disorders and spatial disorientation. Electrophysiological investigations in animals revealed that such deficits are partly due to imbalanced spontaneous activity and sensitivity to motion in neurons located in the ipsilesional and contralesional vestibular nuclei. Neurophysiological reorganizations taking place in the vestibular nuclei are the basis of the decline of the symptoms over time, a phenomenon known as vestibular compensation. Vestibular compensation is facilitated by motor activity and sensory experience, and current rehabilitation programs favor physical activity during the acute stage of a unilateral vestibular loss. Unfortunately, vestibular-defective patients tend to develop strategies in order to avoid movements causing imbalance and nausea (in particular body movements towards the lesioned side), which impedes vestibular compensation. Neuroanatomical evidence suggests a cortical control of postural and oculomotor reflexes based on corticofugal projections to the vestibular nuclei and, therefore, the possibility to manipulate vestibular functions through top-down mechanisms. Based on evidence from neuroimaging studies showing that imagined whole-body movements can activate part of the vestibular cortex, we propose that mental imagery of whole-body rotations to the lesioned and to the healthy side will help rebalancing the activity in the ipsilesional and contralesional vestibular nuclei. Whether imagined whole-body rotations can improve vestibular compensation could be tested in a randomized controlled study in such patients beneficiating, or not, from a mental imagery training. If validated, this hypothesis will help developing a method contributing to reduce postural instability and falls in vestibular-defective patients. Imagined whole-body rotations thus could provide a simple, safe, home-based and self-administered therapeutic method with the potential to overcome the inconvenience related to physical movements.

Chlamydia control activities in Europe: cross-sectional survey

Background: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. Methods: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. Results: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). Conclusion: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes.

Nursing Homes as a Setting for Psychological Practice: Public Policy Perspectives.

Recent federal legislation has provided renewed interest in improving the quality of nursing home care. The lack of both funding and personnel are significant barriers that may keep psychology's disciplinary expertise from being fully used in nursing homes. Nursing homes may be forced to undertake mandated activities (e.g., preadmission screening, nurses aides' training, and evaluation) without psychologists' expertise, relying either on medical practitioners with little knowledge of mental health interventions or on minimally qualified, entry-level mental health workers. Advocates for improved nursing home care must see the links among basic disciplinary skills, interdisciplinary collaboration, and improved care for mentally impaired elderly individuals.

Seasonal variations of ventricular arrhythmia clusters in defibrillator recipients

BACKGROUND: Clustering ventricular arrhythmias are the consequence of acute ventricular electrical instability and represent a challenge in the management of the growing number of patients with an implantable cardioverter-defibrillator (ICD). Triggering factors can rarely be identified. OBJECTIVES: Several studies have revealed seasonal variations in the frequency of cardiovascular events and life-threatening arrhythmias, and we sought to establish whether seasonal factors may exacerbate ventricular electrical instability leading to arrhythmia clusters and electrical storm. METHODS: Two hundred and fourteen consecutive defibrillator recipients were followed-up during 3.3 +/- 2.2 years. Arrhythmia cluster was defined as the occurrence of three or more arrhythmic events triggering appropriate defibrillator therapies within 2 weeks. Time intervals between two clusters were calculated for each month and each season, and were compared using Kruskal-Wallis test and Wilcoxon-Mann-Whitney test with Bonferroni adjustment. RESULTS: During a follow-up of 698 patient years, 98 arrhythmia clusters were observed in 51 patients; clustering ventricular arrhythmias were associated with temporal variables; they occurred more frequently in the winter and spring months than during the summer and fall. Accordingly, the time intervals between two clusters were significantly shorter during winter and spring (median and 95% CI): winter 16 (5-19), spring 11.5 (7-25), summer 34.5 (15-55), fall 50.5 (19-65), P = 0.0041. CONCLUSION: There are important seasonal variations in the incidence of arrhythmia clusters in ICD recipients. Whether these variations are related to environmental factors, change in physical activity, or psychological factors requires further study.

Platelet receptors for adhesion and activation. Variability as a factor in susceptibility to cardiovascular diseases

Polymorphisms in coagulation factors leading to altered susceptibility to cardiovascular diseases have been known for some time and some are now well-established risk factors. More recently, an increasing number of polymorphisms have been identified in platelet receptors and a series of studies indicate that these too may play a role as individual risk factors for stroke and myocardial infarction. The effect of these platelet polymorphisms appears less clear-cut than some of the coagulation factor effects and other, associated, risk factors may be important in defining their role. In this review platelet receptor polymorphisms and their role as risk factors are surveyed and their possible relevance discussed.

Effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation: phantom study

OBJECTIVE: The purpose of this study was to evaluate in a phantom study the effect of patient size on radiation dose for abdominal MDCT with automatic tube current modulation. MATERIALS AND METHODS: One or two 4-cm-thick circumferential layers of fat-equivalent material were added to the abdomen of an anthropomorphic phantom to simulate patients of three sizes: small (cross-sectional dimensions, 18 x 22 cm), average size (26 x 30 cm), and oversize (34 x 38 cm). Imaging was performed with a 64-MDCT scanner with combined z-axis and xy-axis tube current modulation according to two protocols: protocol A had a noise index of 12.5 H, and protocol B, 15.0 H. Radiation doses to three abdominal organs and the skin were assessed. Image noise also was measured. RESULTS: Despite increasing patient size, the image noise measured was similar for protocol A (range, 11.7-12.2 H) and protocol B (range, 13.9-14.8 H) (p > 0.05). With the two protocols, in comparison with the dose of the small patient, the abdominal organ doses of the average-sized patient and the oversized patient increased 161.5-190.6%and 426.9-528.1%, respectively (p < 0.001). The skin dose increased as much as 268.6% for the average-sized patient and 816.3% for the oversized patient compared with the small patient (p < 0.001). CONCLUSION: Oversized patients undergoing abdominal MDCT with tube current modulation receive significantly higher doses than do small patients. The noise index needs to be adjusted to the body habitus to ensure dose efficiency.

1.0-M gadobutrol versus 0.5-M gadoterate for peripheral magnetic resonance angiography: a prospective randomized controlled clinical trial

PURPOSE: To perform a quantitative and qualitative comparison of gadobutrol and gadoterate in three-station contrast enhanced magnetic resonance angiography (CE-MRA) of the lower limbs. MATERIALS AND METHODS: In this prospective randomized controlled trial, 52 patients with leg ischemia were randomly assigned to one of two groups receiving either gadobutrol (1.0 mmol Gd/mL, 15 mL) or gadoterate (0.5 mmol Gd/mL, 30 mL). Three-station 3D CE-MRAs from the pelvis to the ankles were performed with moving-table technique on a 1.5T MR scanner. Injection time was identical in both groups. Signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were calculated for 816 arteries. Contrast quality in 1196 vessel segments was evaluated separately by two blinded readers on a three-point scale. RESULTS: Mean SNR (61.8 +/- 7.8 for gadobutrol vs. 61.9 +/- 9.1 for gadoterate, P = 0.257), CNR (52.8 +/- 9.1 vs. 52.8 +/- 10.7, P = 0.154), and qualitative ranking (1.41 vs. 1.44, P = 0.21) for all vessels did not differ significantly between the two patient groups. The overall quality was good in 90.4% with gadoterate and 94.2% with gadobutrol (P = 0.462). CONCLUSION: High-concentration gadobutrol allows neither a higher CNR nor any qualitative advantage over the ordinary unspecific Gd agent gadoterate when the same Gd load and injection times are used in multistation CE-MRA of the peripheral arteries.

Early prognostic value of the medical emergency team calling criteria in patients admitted to intensive care from the emergency department

OBJECTIVES: To evaluate the early prognostic value of the medical emergency team (MET) calling criteria in patients admitted to intensive care from the emergency department. DESIGN: Retrospective cohort study. SETTING: Emergency department and department of intensive care medicine of a 960-bed tertiary referral hospital. PATIENTS: A total of 452 consecutive adult patients admitted to intensive care from the emergency department from January 1, 2004, to December 31, 2004. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: MET calling criteria were retrospectively extracted from patient records, and the sum of positive criteria was calculated for the first hour in the emergency department (METinitial) and subsequently until admission to the intensive care unit in a series of time periods. The maximum number of positive MET calling criteria during any time period was defined (METmax). Logistic regression analysis revealed METinitial (odds ratio [OR] 3.392, 95% confidence interval [CI] 2.534-4.540) and METmax (OR 3.867, 95% CI 2.816-5.312) to be significant predictors of hospital mortality, the need for mechanical ventilation (METinitial: OR 4.151, 95% CI 3.53-4.652; METmax: OR 4.292, 95% CI 3.151-5.846), and occurrence of hemodynamic instability (METinitial: OR 1.548, 95% CI 1.258-1.905; METmax: OR 1.685, 95% CI 1.355-2.094) (all p < .0001). CONCLUSIONS: MET scores collected early after admission or throughout the stay in the emergency department allow for simple identification of patients at risk of unfavorable outcome during the subsequent intensive care unit stay.