Physical fitness in people with a spinal cord injury: the association with complications and duration of rehabilitation.

Objective: To assess the association between physical fitness and its recovery over time on the one hand, and complications and duration of phases of rehabilitation on the other. Design and setting: Prospective cohort study at eight rehabilitation centres. Subjects: People with a spinal cord injury were assessed four times: at the start of active rehabilitation (n = 110), three months later (n = 92), at discharge (n = 137) and a year after discharge from inpatient rehabilitation (n = 91). Main measures: Physical fitness was defined as aerobic capacity, determined at each occasion by the peak oxygen uptake (peak V

Bifurcation Boundary Conditions for Switching DC-DC Converters Under Constant On-Time Control

Sampled-data analysis and harmonic balance analysis are applied to analyze switching DC-DC converters under constant on-time control. Design-oriented boundary conditions for the period-doubling bifurcation and the saddle-node bifurcation are derived. The required ramp slope to avoid the bifurcations and the assigned pole locations associated with the ramp are also derived. The derived boundary conditions are more general and accurate than those recently obtained. Those recently obtained boundary conditions become special cases under the general modeling approach presented in this paper. Different analyses give different perspectives on the system dynamics and complement each other. Under the sampled-data analysis, the boundary conditions are expressed in terms of signal slopes and the ramp slope. Under the harmonic balance analysis, the boundary conditions are expressed in terms of signal harmonics. The derived boundary conditions are useful for a designer to design a converter to avoid the occurrence of the period-doubling bifurcation and the saddle-node bifurcation.Comment: Submitted to International Journal of Circuit Theory and Applications on August 10, 2011; Manuscript ID: CTA-11-016

Detection of partial-thickness supraspinatus tendon tears: is a single direct MR arthrography series in ABER position as accurate as conventional MR arthrography?

The purpose of this study was to retrospectively evaluate sensitivity and specificity of a single magnetic resonance (MR) arthrography series in abduction external rotation (ABER) position compared with conventional MR arthrography for detection of supraspinatus tendon tears, with arthroscopy as gold standard, and to assess interobserver variability. Institutional review board approval was obtained; informed consent was waived. MR arthrograms of 250 patients (170 men and 80 women; mean age, 36 years) were retrospectively and independently evaluated by three observers. Oblique coronal T1-weighted fat-suppressed images, proton density, and T2-weighted images and axial T1-weighted images and oblique sagittal T1-weighted fat-suppressed images were analyzed to detect supraspinatus tendon tears. Separately, a single T1-weighted fat-suppressed oblique axial series in ABER position was evaluated. Both protocols were scored randomly without knowledge of patients' clinical history and arthroscopy results. Tears were subclassified, based on articular surface integrity and extension (Lee classification). Interobserver agreement was assessed by kappa statistics for all patients. Ninety-two of 250 patients underwent arthroscopy; sensitivity and specificity of ABER and conventional MR arthrography were calculated and compared using paired McNemar test. Weighted kappa values of ABER and conventional MR arthrography were 0.48-0.65 and 0.60-0.67, respectively. According to arthroscopy, 69 of 92 patients had an intact cuff, and 23 patients had a cuff tear (16 partial thickness and seven full thickness). There were no statistically significant differences between ABER and conventional MR arthrography regarding sensitivity (48-61% and 52-70%, respectively) and specificity (80-94% and 91-95%). Sensitivity and specificity of a single T1-weighted series in ABER position and conventional MR arthrography are comparable for assessment of rotator cuff tear

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

The Streptococcus pneumoniae Pilus-1 Displays a Biphasic Expression Pattern

The Streptococcus pneumoniae pilus-1 is encoded by pilus islet 1 (PI-1), which has three clonal variants (clade I, II and III) and is present in about 30% of clinical pneumococcal isolates. In vitro and in vivo assays have demonstrated that pilus-1 is involved in attachment to epithelial cells and virulence, as well as protection in mouse models of infection. Several reports suggest that pilus-1 expression is tightly regulated and involves the interplay of numerous genetic regulators, including the PI-1 positive regulator RlrA. In this report we provide evidence that pilus expression, when analyzed at the single-cell level in PI-1 positive strains, is biphasic. In fact, the strains present two phenotypically different sub-populations of bacteria, one that expresses the pilus, while the other does not. The proportions of these two phenotypes are variable among the strains tested and are not influenced by genotype, serotype, growth conditions, colony morphology or by the presence of antibodies directed toward the pilus components. Two sub-populations, enriched in pilus expressing or not expressing bacteria were obtained by means of colony selection and immuno-detection methods for five strains. PI-1 sequencing in the two sub-populations revealed the absence of mutations, thus indicating that the biphasic expression observed is not due to a genetic modification within PI-1. Microarray expression profile and western blot analyses on whole bacterial lysates performed comparing the two enriched sub-populations, revealed that pilus expression is regulated at the transcriptional level (on/off regulation), and that there are no other genes, in addition to those encoded by PI-1, concurrently regulated across the strains tested. Finally, we provide evidence that the over-expression of the RrlA positive regulator is sufficient to induce pilus expression in pilus-1 negative bacteria. Overall, the data presented here suggest that the observed biphasic pilus expression phenotype could be an example of bistability in pneumococcus

Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages: (i) triggering, (ii) maturation, (iii) targeting, and (iv) fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies (including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs) remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our  understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA

Directed Evaluation of Enterotoxigenic Escherichia coli Autotransporter Proteins as Putative Vaccine Candidates

Diarrheal diseases are responsible for more than 1.5 million deaths annually in developing countries. Enterotoxigenic E. coli (ETEC) are among the most common bacterial causes of diarrhea, accounting for an estimated 300,000–500,000 deaths each year, mostly in young children. There unfortunately is not yet a vaccine that can offer sustained, broad-based protection against ETEC. While most vaccine development effort has focused on plasmid-encoded finger-like ETEC adhesin structures known as colonization factors, additional effort is needed to identify conserved target antigens. Epidemiologic studies suggest that immune responses to uncharacterized, chromosomally encoded antigens could contribute to protection resulting from repeated infections. Earlier studies of immune responses to ETEC infection had identified a class of surface-expressed molecules known as autotransporters (AT). Therefore, available ETEC genome sequences were examined to identify conserved ETEC autotransporters not shared by the commensal E. coli HS strain, followed by studies of the immune response to these antigens, and tests of their utility as vaccine components. Two chromosomally encoded ATs, identified in ETEC, but not in HS, were found to be immunogenic and protective in an animal model, suggesting that conserved AT molecules contribute to protective immune responses that follow natural ETEC infection and offering new potential targets for vaccines