De Novo Assembly of the Pneumocystis jirovecii Genome from a Single Bronchoalveolar Lavage Fluid Specimen from a Patient.

ABSTRACT Pneumocystis jirovecii is a fungus that causes severe pneumonia in immunocompromised patients. However, its study is hindered by the lack of an in vitro culture method. We report here the genome of P. jirovecii that was obtained from a single bronchoalveolar lavage fluid specimen from a patient. The major challenge was the in silico sorting of the reads from a mixture representing the different organisms of the lung microbiome. This genome lacks virulence factors and most amino acid biosynthesis enzymes and presents reduced GC content and size. Together with epidemiological observations, these features suggest that P. jirovecii is an obligate parasite specialized in the colonization of human lungs, which causes disease only in immune-deficient individuals. This genome sequence will boost research on this deadly pathogen. IMPORTANCE Pneumocystis pneumonia is a major cause of mortality in patients with impaired immune systems. The availability of the P. jirovecii genome sequence allows new analyses to be performed which open avenues to solve critical issues for this deadly human disease. The most important ones are (i) identification of nutritional supplements for development of culture in vitro, which is still lacking 100 years after discovery of the pathogen; (ii) identification of new targets for development of new drugs, given the paucity of present treatments and emerging resistance; and (iii) identification of targets for development of vaccines.

The History of the Establishment of the Division of Child Welfare of the Social Welfare Department of the State of Iowa, 1938

History of Child Welfare Legislation in the State of Iowa 1838-1898; Establishment of the Iowa State board of Control in 1898 and its influence on Child Welfare Legislation until 1925; Immediate background, organizing and the administration functions of the Child Welfare Division of the Social Welfare Department of the State of Iowa. NOTE: This document has pagination errors.

Mycoplasma hominis necrotizing pleuropneumonia in a previously healthy adolescent.

BACKGROUND: Mycoplasma hominis is a fastidious micro-organism causing systemic infections in the neonate and genital infections in the adult. It can also be the cause of serious extra-genital infections, mainly in immunosuppressed or predisposed subjects. CASE PRESENTATION: We describe a case of severe pneumonia and pericarditis due to Mycoplasma hominis in a previously healthy adolescent who did not respond to initial therapy. CONCLUSIONS: Mycoplasma hominis could be an underestimated cause of severe pneumonia in immunocompetent patients and should be particularly suspected in those not responding to standard therapy.

A qui administrer le vaccin anti-pneumococcique? [We should received and pneumococcal immunization?]

Alors que l'immunisation active contre l'influenza semble être actuellement largement entrée dans la pratique médicale, force est de constater que c'est loin d'être le cas pour les infections à pneumocoque. La vaccination anti-pneumocoque. La vaccination anti-pneumococcique, qui est incluse dans les schémas d'immunisation de nombreux pays, ne fait actuellement pas l'objet de recommendations particulières en Suisse et son utilisation y reste marginale. Compte tenu du nombre élevé d'infections sévères et de décès potentiellement évitables, sa généralisation à tous les groupes à risque doit être encouragée. De plus, cette stratégie pourrait se révéler utile face à la progression inexorable de la proportion de souches résistantes à la pénicilline et aux autres microbes.

Bayesian image reconstruction with space-variant noise suppression

In this paper we present a Bayesian image reconstruction algorithm with entropy prior (FMAPE) that uses a space-variant hyperparameter. The spatial variation of the hyperparameter allows different degrees of resolution in areas of different statistical characteristics, thus avoiding the large residuals resulting from algorithms that use a constant hyperparameter. In the first implementation of the algorithm, we begin by segmenting a Maximum Likelihood Estimator (MLE) reconstruction. The segmentation method is based on using a wavelet decomposition and a self-organizing neural network. The result is a predetermined number of extended regions plus a small region for each star or bright object. To assign a different value of the hyperparameter to each extended region and star, we use either feasibility tests or cross-validation methods. Once the set of hyperparameters is obtained, we carried out the final Bayesian reconstruction, leading to a reconstruction with decreased bias and excellent visual characteristics. The method has been applied to data from the non-refurbished Hubble Space Telescope. The method can be also applied to ground-based images.

Head-to-head comparison of length of stay, patients' outcome and satisfaction in Switzerland before and after SwissDRG-Implementation in 2012 in 2012: an observational study in two tertiary university centers.

On 1 January 2012 Swiss Diagnosis Related Groups (DRG), a new uniform payment system for in-patients was introduced in Switzerland with the intention to replace a "cost-based" with a "case-based" reimbursement system to increase efficiency. With the introduction of the new payment system we aim to answer questions raised regarding length of stay as well as patients' outcome and satisfaction. This is a prospective, two-centre observational cohort study with data from University Hospital Basel and the Cantonal Hospital Aarau, Switzerland, from January to June 2011 and 2012, respectively. Consecutive in-patients with the main diagnosis of either community-acquired pneumonia, exacerbation of COPD, acute heart failure or hip fracture were included. A questionnaire survey was sent out after discharge investigating changes before and after SwissDRG implementation. Our primary endpoint was LOS. Of 1,983 eligible patients 841 returned the questionnaire and were included into the analysis (429 in 2011, 412 in 2012). The median age was 76.7 years (50.8% male). Patients in the two years were well balanced in regard to main diagnoses and co-morbidities. Mean LOS in the overall patient population was 10.0 days and comparable between the 2011 cohort and the 2012 cohort (9.7 vs 10.3; p = 0.43). Overall satisfaction with care changed only slightly after introduction of SwissDRG and remained high (89.0% vs 87.8%; p = 0.429). Investigating the influence of the implementation of SwissDRG in 2012 regarding LOS patients' outcome and satisfaction, we found no significant changes. However, we observed some noteworthy trends, which should be monitored closely.

Prevalence of respiratory viruses among febrile children with or without acute respiratory symptoms in Tanzania

Background Respiratory viruses are the most frequent cause of febrile illnesses in infants and young children but few investigations have assessed their impact and epidemiology in Africa . We investigated their rate in febrile outpatient children attending in Tanzania. Methods Children aged 2 months -10 years with fever >38 _C were recruited prospectively between April and December 2008. Medical history and clinical examination were recorded in a standardized fashion and nasopharyngeal swabs analyzed for the presence of 12 viruses by real-time PCR (FLUAV, FLUBV, RSV, MPV, HPIV-1/3, four types of HCoV, HBoV, PIC and HAdV). Ct values were used to provide semi-quantitative viral loads.Results Of 1005 febrile children enrolled, 623 (62%) had respiratory symptoms (URTI in 66%, bronchiolitis in 7% and clinical pneumonia in 27%); 156 (16%) had febrile illness that remained of unspecified etiology and 226 (22%) had other infectious diseases and no ARI (62 malaria, 56 gastroenteritis, 36 urinary tract and 72 others). The proportions of patients with at least one respiratory virus were 70%, 61% and 47% (Pvalue < 0.001) in these three groups. When excluding picornavirus and adenovirus these proportions were 48%, 24% and 26% (P-value < 0.001). Apart from picornavirus and adenovirus, influenza A and B viruses were the most frequent followed by coronavirus and RSV. The proportion of children with presumably high viral titers (Ct < 25) was higher in the group with respiratory symptoms (31%) than in the two other groups (21% and 16%). Influenza genotyping revealed strains that were similar to the ones circulating elsewhere in the world.Conclusion In African children with febrile illness, the prevalence of respiratory viruses, especially influenza A and B, is high particularly in the presence of respiratory symptoms, but also, although less so, in those with unspecified etiology or other infectious diseases. This highlights that these viruses are commonly circulating in Tanzanian children.

Time-scale and other invariants of integrative mechanical behavior in living cells.

In dealing with systems as complex as the cytoskeleton, we need organizing principles or, short of that, an empirical framework into which these systems fit. We report here unexpected invariants of cytoskeletal behavior that comprise such an empirical framework. We measured elastic and frictional moduli of a variety of cell types over a wide range of time scales and using a variety of biological interventions. In all instances elastic stresses dominated at frequencies below 300 Hz, increased only weakly with frequency, and followed a power law; no characteristic time scale was evident. Frictional stresses paralleled the elastic behavior at frequencies below 10 Hz but approached a Newtonian viscous behavior at higher frequencies. Surprisingly, all data could be collapsed onto master curves, the existence of which implies that elastic and frictional stresses share a common underlying mechanism. Taken together, these findings define an unanticipated integrative framework for studying protein interactions within the complex microenvironment of the cell body, and appear to set limits on what can be predicted about integrated mechanical behavior of the matrix based solely on cytoskeletal constituents considered in isolation. Moreover, these observations are consistent with the hypothesis that the cytoskeleton of the living cell behaves as a soft glassy material, wherein cytoskeletal proteins modulate cell mechanical properties mainly by changing an effective temperature of the cytoskeletal matrix. If so, then the effective temperature becomes an easily quantified determinant of the ability of the cytoskeleton to deform, flow, and reorganize.

A dynamic model for stem cell homeostasis and patterning in Arabidopsis meristems.

Plants maintain stem cells in their meristems as a source for new undifferentiated cells throughout their life. Meristems are small groups of cells that provide the microenvironment that allows stem cells to prosper. Homeostasis of a stem cell domain within a growing meristem is achieved by signalling between stem cells and surrounding cells. We have here simulated the origin and maintenance of a defined stem cell domain at the tip of Arabidopsis shoot meristems, based on the assumption that meristems are self-organizing systems. The model comprises two coupled feedback regulated genetic systems that control stem cell behaviour. Using a minimal set of spatial parameters, the mathematical model allows to predict the generation, shape and size of the stem cell domain, and the underlying organizing centre. We use the model to explore the parameter space that allows stem cell maintenance, and to simulate the consequences of mutations, gene misexpression and cell ablations.

Cross-neutralization of four paramyxoviruses by a human monoclonal antibody.

Broadly neutralizing antibodies reactive against most and even all variants of the same viral species have been described for influenza and HIV-1 (ref. 1). However, whether a neutralizing antibody could have the breadth of range to target different viral species was unknown. Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are common pathogens that cause severe disease in premature newborns, hospitalized children and immune-compromised patients, and play a role in asthma exacerbations. Although antisera generated against either HRSV or HMPV are not cross-neutralizing, we speculated that, because of the repeated exposure to these viruses, cross-neutralizing antibodies may be selected in some individuals. Here we describe a human monoclonal antibody (MPE8) that potently cross-neutralizes HRSV and HMPV as well as two animal paramyxoviruses: bovine RSV (BRSV) and pneumonia virus of mice (PVM). In its germline configuration, MPE8 is HRSV-specific and its breadth is achieved by somatic mutations in the light chain variable region. MPE8 did not result in the selection of viral escape mutants that evaded antibody targeting and showed potent prophylactic efficacy in animal models of HRSV and HMPV infection, as well as prophylactic and therapeutic efficacy in the more relevant model of lethal PVM infection. The core epitope of MPE8 was mapped on two highly conserved anti-parallel β-strands on the pre-fusion viral F protein, which are rearranged in the post-fusion F protein conformation. Twenty-six out of the thirty HRSV-specific neutralizing antibodies isolated were also found to be specific for the pre-fusion F protein. Taken together, these results indicate that MPE8 might be used for the prophylaxis and therapy of severe HRSV and HMPV infections and identify the pre-fusion F protein as a candidate HRSV vaccine.

Endovascular aortic repair versus open surgical repair for descending thoracic aortic disease a systematic review and meta-analysis of comparative studies.

OBJECTIVES: The purpose of this study was to determine whether thoracic endovascular aortic repair (TEVAR) reduces death and morbidity compared with open surgical repair for descending thoracic aortic disease. BACKGROUND: The role of TEVAR versus open surgery remains unclear. Metaregression can be used to maximally inform adoption of new technologies by utilizing evidence from existing trials. METHODS: Data from comparative studies of TEVAR versus open repair of the descending aorta were combined through meta-analysis. Metaregression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Due to significant heterogeneity, registry data were analyzed separately from comparative studies. RESULTS: Forty-two nonrandomized studies involving 5,888 patients were included (38 comparative studies, 4 registries). Patient characteristics were balanced except for age, as TEVAR patients were usually older than open surgery patients (p = 0.001). Registry data suggested overall perioperative complications were reduced. In comparative studies, all-cause mortality at 30 days (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.33 to 0.59) and paraplegia (OR: 0.42, 95% CI: 0.28 to 0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction, aortic reintervention, and mortality beyond 1 year. Metaregression to adjust for age imbalance, study design, and pathology did not materially change the results. CONCLUSIONS: Current data from nonrandomized studies suggest that TEVAR may reduce early death, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. Sustained benefits on survival have not been proven.

Development of a high throughput PCR to detect Coxiella burnetii and its application in a diagnostic laboratory over a 7-year period.

Q fever is a worldwide zoonotic infectious disease due to Coxiella burnetii. The clinical presentation may be acute (pneumonia and/or hepatitis) or chronic (most commonly endocarditis). Diagnosis mainly relies on serology and PCR. We therefore developed a quantitative real-time PCR. We first tested blindly its performance on various clinical samples and then, when thoroughly validated, we applied it during a 7-year period for the diagnosis of both acute and persistent C. burnetii infection. Analytical sensitivity (< 10 copies/PCR) was excellent. When tested blindly on 183 samples, the specificity of the PCR was 100% (142/142) and the sensitivity was 71% (29/41). The sensitivity was 88% (7/8) on valvular samples, 69% (20/29) on blood samples and 50% (2/4) on urine samples. This new quantitative PCR was then successfully applied for the diagnosis of acute Q fever and endovascular infection due to C. burnetii, allowing the diagnosis of Q fever in six patients over a 7-year period. During a local small cluster of cases, the PCR was also applied to blood from 1355 blood donors; all were negative confirming the high specificity of this test. In conclusion, we developed a highly specific method with excellent sensitivity, which may be used on sera for the diagnosis of acute Q fever and on various samples such as sera, valvular samples, aortic specimens, bone and liver, for the diagnosis of persistent C. burnetii infection.

BIO-INSPIRED COMPUTATIONAL TECHNIQUES APPLIED TO THE CLUSTERING AND VISUALIZATION OF SPATIO-TEMPORAL GEOSPATIAL DATA

The coverage and volume of geo-referenced datasets are extensive and incessantly¦growing. The systematic capture of geo-referenced information generates large volumes¦of spatio-temporal data to be analyzed. Clustering and visualization play a key¦role in the exploratory data analysis and the extraction of knowledge embedded in¦these data. However, new challenges in visualization and clustering are posed when¦dealing with the special characteristics of this data. For instance, its complex structures,¦large quantity of samples, variables involved in a temporal context, high dimensionality¦and large variability in cluster shapes.¦The central aim of my thesis is to propose new algorithms and methodologies for¦clustering and visualization, in order to assist the knowledge extraction from spatiotemporal¦geo-referenced data, thus improving making decision processes.¦I present two original algorithms, one for clustering: the Fuzzy Growing Hierarchical¦Self-Organizing Networks (FGHSON), and the second for exploratory visual data analysis:¦the Tree-structured Self-organizing Maps Component Planes. In addition, I present¦methodologies that combined with FGHSON and the Tree-structured SOM Component¦Planes allow the integration of space and time seamlessly and simultaneously in¦order to extract knowledge embedded in a temporal context.¦The originality of the FGHSON lies in its capability to reflect the underlying structure¦of a dataset in a hierarchical fuzzy way. A hierarchical fuzzy representation of¦clusters is crucial when data include complex structures with large variability of cluster¦shapes, variances, densities and number of clusters. The most important characteristics¦of the FGHSON include: (1) It does not require an a-priori setup of the number¦of clusters. (2) The algorithm executes several self-organizing processes in parallel.¦Hence, when dealing with large datasets the processes can be distributed reducing the¦computational cost. (3) Only three parameters are necessary to set up the algorithm.¦In the case of the Tree-structured SOM Component Planes, the novelty of this algorithm¦lies in its ability to create a structure that allows the visual exploratory data analysis¦of large high-dimensional datasets. This algorithm creates a hierarchical structure¦of Self-Organizing Map Component Planes, arranging similar variables' projections in¦the same branches of the tree. Hence, similarities on variables' behavior can be easily¦detected (e.g. local correlations, maximal and minimal values and outliers).¦Both FGHSON and the Tree-structured SOM Component Planes were applied in¦several agroecological problems proving to be very efficient in the exploratory analysis¦and clustering of spatio-temporal datasets.¦In this thesis I also tested three soft competitive learning algorithms. Two of them¦well-known non supervised soft competitive algorithms, namely the Self-Organizing¦Maps (SOMs) and the Growing Hierarchical Self-Organizing Maps (GHSOMs); and the¦third was our original contribution, the FGHSON. Although the algorithms presented¦here have been used in several areas, to my knowledge there is not any work applying¦and comparing the performance of those techniques when dealing with spatiotemporal¦geospatial data, as it is presented in this thesis.¦I propose original methodologies to explore spatio-temporal geo-referenced datasets¦through time. Our approach uses time windows to capture temporal similarities and¦variations by using the FGHSON clustering algorithm. The developed methodologies¦are used in two case studies. In the first, the objective was to find similar agroecozones¦through time and in the second one it was to find similar environmental patterns¦shifted in time.¦Several results presented in this thesis have led to new contributions to agroecological¦knowledge, for instance, in sugar cane, and blackberry production.¦Finally, in the framework of this thesis we developed several software tools: (1)¦a Matlab toolbox that implements the FGHSON algorithm, and (2) a program called¦BIS (Bio-inspired Identification of Similar agroecozones) an interactive graphical user¦interface tool which integrates the FGHSON algorithm with Google Earth in order to¦show zones with similar agroecological characteristics.