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An approximate formulation to determine the amount of transverse reinforcement for columns of reinforced concrete (RC) frames in seismic areas is presented. It is based on observations that suggested that the main function of transverse reinforcement is to confine the core subjected to a complex state of stresses rather than simply resist shear or improve deformability under axial compression. The combined effects of shear and axial stresses are assumed to be a function of the maximum drift ratio and they are interpreted using Coulomb’s failure criterion. A comparison between results obtained with the model developed and current design recommendations suggests that the required amount of transverse reinforcement specified in ACI 318-95 can be reduced safely for “flexible” columns (ratio of column height to effective depth ≅6) under low amplitude displacement cycles (ratio of lateral displacement to column height ≤3%) and “short” columns (ratio of column height to effective depth ≅4) under combinations of relatively low shear and axial stresses.

In a recent study, 25 development-length tests were conducted on rectangular and T-shaped semilightweight beams having design compressive strengths of 48 MPa (7,000 psi) and 69 MPa (10,000 psi). In the rectangular beam tests, the design moment capacity was exceeded in every case. However, in the tests on T-shaped beams, bond failure occurred in some specimens immediately after the formation of a flexure-shear crack. Additional tests were then conducted on similar T-shaped beams having varying amounts of transverse reinforcement near the point load. These tests showed that bond failure could be prevented by increasing the transverse reinforcement near the point of maximum moment. The study showed that the shift in the tension force that occurs when flexural cracks turn diagonally may lead to bond failure if sufficient anchorage of the strand is not provided. Therefore, the investigators recommend that the current AASHTO requirements for strand development be enforced at a “critical section” located at a distance dp from the point of maximum moment toward the free end of the strand, where dp is the distance from the extreme compression fiber to the centroid of the prestressed reinforcement.

The results from a research project that evaluated the long-term performance of bridges constructed with composite prestressed concrete panels are summarized. The particular construction system investigated used full-span prestressed concrete panels that would be typical for bridges with spans of 12 m (40 ft) or less. A full-scale bridge specimen was constructed and subjected to 5 million cycles of service loading and 48 weeks of durability exposure cycling. This was done to assess the potential for delamination as well as the resistance to chloride-induced reinforcement corrosion. The exposure cycling greatly accelerated the rate of penetration of chlorides, producing concentrations in the deck that exceeded those from bridges that had been in service for nearly 40 years. The results from this study showed that long-term composite behavior can be achieved in these structures by applying a raked finish to the top surface of the prestressed panels. Corrosion measurements revealed the need to modify the positive-moment connections at interior piers to provide a more durable structure.

We have previously shown that different isolates of Chlamydia pneumoniae display heterogeneity in the in vitro stimulation of chemokines and adhesion molecules from infected human endothelial cells. In the present study, we examined the ability of different isolates of C. pneumoniae to promote transendothelial migration of neutrophils and monocytes. Human umbilical vein endothelial cells (HUVEC) were infected with low (C. pneumoniae isolates A-03, PS-32, and BR-393 and high (>40)-passage isolates BAL-16, TW-183, and T-2634, and levels of neutrophil and monocyte transendothelial migration were determined following 24 h of infection. Compared to mock-infected controls, significant increases in neutrophil migration were observed in response to most C. pneumoniae isolates examined ( P < 0.001). Levels of monocyte migration were significantly increased in response to TW-183 and T-2634 ( P < 0.001). Serial passage (>40 times) of the three low-passage isolates in HEp-2 cell cultures prior to infection of HUVEC generally resulted in the promotion of higher levels of neutrophil and monocyte transendothelial migration. These findings were compatible with differences observed in the extent of interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) stimulation between low- and high-passage A-03, PS-32, and BR-393. As opposed to C. pneumoniae , infection with C. trachomatis L2 caused only a slight increase in neutrophil transendothelial migration, which correlated with the lack of measurable IL-8 levels by this species. However, significant levels of monocyte migration were induced in response to C. trachomatis L2 despite a lack of measurable MCP-1 stimulation. C. trachomatis serovars A and E also failed to induce IL-8 and MCP-1 production in HUVEC. Results from this study indicate that the passage history of C. pneumoniae may play a role in the divergence of stimulatory activities observed among isolates in human endothelial cells. In addition, the differences observed between this organism and C. trachomatis suggest that the upregulation of IL-8 and MCP-1 in endothelial cells may be unique to C. pneumoniae .

Five hundred and forty patients with severe infection were enrolled in a multicentre, prospective, randomized, non-blinded study to compare the efficacy and safety of iv ciprofloxacin with iv standard therapy. Five hundred and thirty-one patients received at least one dose of study drug for pneumonia (310), septicaemia (112) or skin and skin structure infection (109). Intravenous ciprofloxacin (400 mg, every 8 h) or iv ciprofloxacin (400 mg, every 8 h) plus a β-lactam were compared with a standard monotherapy (β-lactam) or combination (aminoglycoside plus a β-lactam) therapy. Patients were treated parenterally for a minimum of 2 or 3 days, then at the discretion of the investigator could be switched to oral therapy (ciprofloxacin 750 mg, every 12 h or a standard oral therapy). Patients were randomized in the ratio of 2:1 for the ciprofloxacin and standard therapy treatment groups and stratified to monotherapy if the APACHE II score was ≤20 or to combination therapy if the APACHE II score was 21- 29. Three hundred and ninety-five (74%) patients were valid for the efficacy analysis: these comprised 242 pneumonia (167 ciprofloxacin and 75 standard therapy), 70 septicaemia (47 ciprofloxacin and 23 standard therapy), and 83 skin infections (56 ciprofloxacin and 27 standard). The primary efficacy variable was clinical response and the secondary efficacy assessment was bacteriological response at the end of therapy (2 or 3 days after treatment). The mean duration of therapy for patients receiving only iv monotherapy or combination therapy was shorter (9- 10 days) than for patients receiving sequential iv/po therapy (14- 17 days). At the end of therapy, overall clinical resolution/improvement (success) for monotherapy was 138/166 (83%) for the ciprofloxacin group, compared with 74/87 (85%) for standard-treated patients (95% CI =−11.5% to 7.6%), and for combination therapy the response was 43/51 (84%) for the ciprofloxacin group and 14/20 (70%) for standard-treated patients (95% CI =− 6.3% to 34.9%). For pneumonia, the most frequent infection treated, clinical success rates following monotherapy were 85% for ciprofloxacin and 83% for standard-treated patients and 83% for ciprofloxacin compared with 69% for standard-treated patients in the combination therapy group. Bacteriological eradication/presumed eradication following monotherapy was 85/102 (83%) for ciprofloxacin and 31/46 (67%) for standard-treated patients (95% CI = 1.6% to 30.3%), and that for combination therapy was 29/36 (81%) for ciprofloxacin and 7/10 (70%) for standard-treated patients (95% CI =−18.3% to 39.5%). Drug-related adverse events, primarily diarrhoea and nausea, were reported in 22% of ciprofloxacin-treated patients and 20% of standard-treated patients. In summary, ciprofloxacin administered alone or in combination was found to be effective in treating a wide range of severe infections.

Community-acquired pneumonia remains a significant health concern despite the availability of effective antibiotics. This randomized, double-masked, double-dummy, multicenter comparative trial was undertaken to compare the efficacy and safety of sparfloxacin with those of clarithromycin in the treatment of community-acquired pneumonia. In 54 centers throughout the United States, 342 patients aged > or = 18 years with community-acquired pneumonia were enrolled in this trial. A total of 167 patients, 98 males and 69 females with a mean age of 51.0 years (range, 18-87), received a 400-mg loading dose of sparfloxacin on the first day, followed by 200 mg once daily for a total of 10 days. A total of 175 patients, 85 males and 90 females with a mean age of 51.3 years (range, 18-91), received clarithromycin 250 mg twice daily for 10 days. In the intent-to-treat population, 133 (79.6%) patients in the sparfloxacin group and 145 (82.9%) in the clarithromycin group were cured or improved (the 95% confidence interval [CI] for the differences in success rate between sparfloxacin and clarithromycin was -11.5% to 5.1%). Success rates for the per-protocol patients were 88.7% (133/150) in the sparfloxacin group and 88.9% (144/162) in the clarithromycin groups (95% CI, -7.2% to 6.8%). There were no significant differences in success rate between treatment groups based on age > or = 65 years. The overall bacteriologic response rates in the bacteriologically assessable population were 97.0% (64/66 isolates) in the sparfloxacin group and 91.4% (74/81 isolates) in the clarithromycin group. Recurrence occurred in 6.0% of per-protocol patients in the sparfloxacin group and 6.3% of patients in the clarithromycin group. The overall frequency of adverse events was 56.3% in the sparfloxacin group and 65.1% in the clarithromycin group. Gastrointestinal disturbances were the most common adverse event in both groups. Abnormal taste related to study drug was reported by 17 patients (9.7%) treated with clarithromycin, versus 3 patients (1.8%) treated with sparfloxacin (P = 0.002). Photosensitivity reactions were reported in 10 patients (6.0%) treated with sparfloxacin, versus 1 patient (0.6%) treated with clarithromycin (P = 0.002). QT-interval prolongation was documented in 4 patients (2.4%) in the sparfloxacin group and no patients in the clarithromycin group. Thus sparfloxacin was as well tolerated and as effective as clarithromycin in the treatment of community-acquired pneumonia.

Some literature suggests that outcomes of CAP in patients with solid tumor without neutropenia may be better than in cancer patients with neutropenia. In order to investigate the role of neutrophils in this population, we retrospectively analyzed consecutive patients with CAP admitted to 3 tertiary care hospitals from 01/2001 through 12/2005. HIV patients were excluded. A total of 993 patients were classified as follows: Group 1: no active cancer; Group 2: solid cancer without neutropenia; Group 3: solid cancer without neutropenia or hematologic malignancy. Age, Pneumonia Severity Index (PSI), overall mortality, time to reach clinical stability (TCS) and length of stay in hospital (LOS) are summarized in the table. No significant differences were found for any of the outcomes between group 2 and 3. Our results suggest that physicians should aggressively manage cancer patients with CAP, regardless of the neutrophil count.

Chlamydia pneumoniae is a respiratory pathogen that has been associated with chronic inflammatory diseases such as asthma and atherosclerosis. Recent isolation of C. pneumoniae from human carotid and coronary atheromas provides additional support for a role of this organism in atherogenesis. We characterized the coronary strain C. pneumoniae A-03 by sequence analysis of the major outer membrane protein gene ( omp1 ). In addition, the in vitro activities of A-03 and three respiratory strains of C. pneumoniae (BAL-16, TW-183, and T-2634) were examined in infected human umbilical vein endothelial cells (HUVEC) by analysis of the production of interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and soluble intercellular cell adhesion molecule 1 (sICAM-1). Sequence analysis of omp1 of C. pneumoniae A-03, compared to prototype strains TW-183 and AR-39, revealed five nucleotide changes resulting in nonsynonymous codons. Of interest was a nonconservative amino acid substitution (Ser to Pro) in position 61 of variable segment 1. In vitro, the extent of MCP-1, IL-8, and sICAM-1 production was dependent on the C. pneumoniae strain examined at low multiplicities of infection following 24 h of incubation. Strain A-03 displayed the lowest stimulatory activity in infected HUVEC, while T-2634 induced the highest levels of MCP-1, IL-8, and sICAM-1 among all strains examined. Heat-inactivated C. pneumoniae failed to stimulate production of these proteins by all strains tested. In contrast, only partial inhibition was observed by UV-inactivated organisms. Results from this study demonstrate that unlike prototype respiratory strains of C. pneumoniae , the coronary strain A-03 displays divergence in the omp1 gene. In addition, the stimulation of chemokines and adhesion molecules involved in the recruitment of leukocytes to sites of inflammation by C. pneumoniae may be important in the pathogenesis of diseases associated with this organism, including atherosclerosis.

An experimental investigation was conducted to evaluate the behavior and strength of bridges constructed with full-span prestressed concrete form panels. This paper addresses the behavior under repeated service loadings and ultimate strength of this type of bridge. Two full-scale specimens were fabricated and subjected to 5 million cycles of service loading before being loaded to failure. It was concluded that these composite bridges will perform adequately under repeated service loadings when composite action between the precast panels and a cast-in-place topping is achieved by applying a raked finish to the precast panels. The full design moment capacities were developed in each specimen after the 5 million cycles of service load had been applied. These ultimate capacities were found to be independent of the moments induced by the restraint of time-dependent deformations.

As already outlined in this supplement,[1] the effective management of serious infections in hospitalised patients poses a complex problem for the clinician. Correct diagnosis and appropriate treatment (selection of an antibiotic to which the suspected pathogens are sensitive, its prompt administration at the correct dosage, together with adequate supportive therapy) are critical for ensuring a favourable patient outcome. In addition, the continuing emergence of resistance among bacteria through chromosomal changes or by exchange of genetic material (transformation, transduction or conjugation) continues to be a major concern.[2-4] This further complicates the treatment of severe infections, as many different organisms (e.g. Pseudomonas aeruginosa, staphylococci, streptococci, enterococci, and Gram-negative bacilli) and different drug classes are involved. The end result is greater morbidity with associated increased healthcare costs and higher mortality among afflicted patients.[3,4] It is against this background that new fluoroquinolone agents, such as clinafloxacin, may have a role to play. Clinafloxacin is a broad-spectrum quinolone antibiotic for parenteral and oral administration. Its spectrum of in vitro activity encompasses many pathogens commonly isolated from hospitalised patients, including drug-resistant strains (e.g. methicillin-resistant Staphylococcus aureus and some multiresistant strains of enterococci).[5] Importantly, quinolone resistance seems to affect the activity of clinafloxacin less than it does the activities of other established fluoroquinolone agents,[6-8] indicating that it may be useful at institutions with emerging resistance to this drug class. The objective of this report is to outline currently available data and ongoing clinical trials evaluating the role of clinafloxacin as empirical therapy, as therapy for known pathogens or as switch (intravenous to oral) therapy in hospitalised patients with serious infections.

A case of Streptococcus pneumoniae combined with Klebsiella pneumoniae as a mixed infection in a patient with community-acquired pneumonia is presented. Community-acquired pneumonia due to combined etiology should be considered in patients who develop clinical deterioration on pathogen-specific therapy against S. pneumoniae.

The objective of this analysis was to evaluate the association between gender and clinical outcomes in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) since data thus far are controversial.Data from a convenience sample of ICU patients with HAP, including ventilator-associated and health care-associated pneumonia, were retrospectively collected from four academic institutions (Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia [IMPACT-HAP] study). Outcomes included 28-day mortality, clinical failure at day 14, hospital and ICU length of stay (LOS), and duration of mechanical ventilation. We compared baseline characteristics and performed multivariate analysis to identify factors independently associated with mortality.Among 416 patients, 271 were men and 145 were women. Women were older (62.4±16.9 vs. 55.7±16.5 years, p0.001) and more critically ill, with Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 21 vs. 19 (p=0.004). Day-28 mortality was 30% for women and 24% for men (p=0.25). Increased 28-day mortality was associated with severity of illness, age, ventilator-associated pneumonia, vascular disease, and hospital LOS prior to pneumonia diagnosis. No significant differences were found in the distribution of bacteria pathogens or in clinical failure rates (36% vs. 31%) between genders. Duration in days of mechanical ventilation, ICU LOS and hospital LOS after the diagnosis of pneumonia were not significantly different between men and women. Analyzing data for women based on presumed pre- or postmenopausal status (age breakpoint of 50 years), showed an increased in ICU LOS (15 vs. 25 days; p=0.0026) and hospital LOS (22 vs. 30 days; p=0.05) for women ≤50 years. No differences were noted in 28-day mortality (24.3% vs. 13.1%; p=0.18) in women ≤50 years of age.In ICU patients with pneumonia, female gender was not associated with worse outcomes or increased resource utilization compared to male gender. Further studies are needed to evaluate menopausal status and outcomes in women with pneumonia.

Background The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) to prevent hospitalizations due to Streptococcus pneumoniae community-acquired pneumonia (SpCAP) is controversial. Recent literature suggests that vaccine effectiveness may be influenced by sex. In this study, we define the effectiveness of prior PPV23 vaccination for the prevention of hospitalizations due to SpCAP, and evaluate the impact of sex on this effectiveness. Methods This was a nested case–control study from the CAPO international cohort study database. SpCAP was defined as CAP plus S. pneumoniae identified in blood, bronchoalveolar lavage, sputum, or urinary antigen. Vaccination with PPV23 prior to hospitalization was defined as documented in the medical record. A propensity score-weighted logistic regression model was used to calculate odds ratios. The adjusted vaccine effectiveness (aVE) was calculated as 1-adjusted odds ratio. Results From a total of 2688 elderly adult hospitalized patients with CAP, SpCAP was identified in 279 (10%). The overall aVE was 37% (95% CI: 10.1–55.4%, P = 0.01). For males, the aVE was 34% (95% CI:−1.0% to 57.3%, P = 0.06). For females the aVE was 68% (95% CI: 40.3–83.0%, P = 0.001). Conclusions PPV23 protects elderly patients from hospitalization due to SpCAP, but female sex drives the effectiveness. Future analysis of vaccine trials should consider the importance of sex as a stratification factor.

We report on the generation of liquid columns that extend far beyond the traditional Rayleigh-Plateau instability onset. The columns are driven by the acoustic pressure wave emitted after bubble collapse. A high-speed video imaging device, which records images at a rate of up to 105 fps, was employed to follow their dynamics. These bubbles, commonly termed thermocavitation bubbles, are generated by focusing a midpower (275 mW) continuous wavelength laser into a highly absorbing liquid droplet. A simple model of the propagation of the pressure wavefront emitted after the bubble collapse shows that focusing the pressure wave at the liquid-air interface drives the evolution of the liquid columns. Control over the aspect ratio of the liquid column is realized by adjusting the cavitation bubble's size, beam focus position, and droplet volume. © 2013 by Begell House, Inc.

Purpose Transgenic manipulation of mouse physiology facilitates the preclinical study of genetic risk factors, neural plasticity, and reactive processes accompanying Alzheimer's disease. Alternatively, entorhinal cortex lesions (ECLs) model pathophysiological denervation and axonal sprouting in rat. Given reports of anatomical differences between the mouse and rat hippocampus, application of the ECL paradigm to transgenic mice first requires comprehensive characterization of axonal sprouting in the wild-type. Methods Adult male C57BL/6 mice sustained unilateral transections of the perforant pathway. Subjects were sacrificed at 1, 4, 10, 18, and 28 days postlesion, and hippocampal sections were stained for AChE, the postsynaptic terminal marker drebrin, and the presynaptic terminal proteins SNAP-25, GAP-43, synapsin, and synaptophysin. To examine synaptic turnover and reinnervation, ipsilateral-to-contralateral staining densities were determined within the dentate molecular layer, and shrinkage-corrected ratios were compared to 28 day-yoked sham cases. Results At 28 days postlesion, ipsilateral terminal marker densities exhibited significant depression. In contrast, qualitative analyses at earlier time points suggested altered AChE staining patterns and increased SNAP-25 and synapsin immunoreactivity in the inner molecular layer (IML) of the dentate gyrus. Conclusions C57BL/6 mice exhibit synaptic reorganization following perforant path transections. The IML may provide a key target for evaluation and intervention in ECL mouse models.

Psoriatic arthritis, a chronic inflammatory musculoskeletal disease that is associated with psoriasis, causes joint erosions, accompanied by loss of function and quality-of-life. The clinical presentation is variable, with extreme phenotypes that can mimic rheumatoid arthritis or ankylosing spondylitis. Because psoriasis usually presents before psoriatic arthritis, the dermatologist plays a key role in early detection of the latter. As many treatments used in psoriasis are also used in psoriatic arthritis, treatment recommendations should take into consideration the type and severity of both conditions. This consensus paper presents guidelines for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists. The paper was drafted by a multidisciplinary group (6rheumatologists, 6dermatologists, and 2epidemiologists) using the Delphi method and contains recommendations, tables, and algorithms for the diagnosis, referral, and treatment of patients with psoriatic arthritis.

In a previous phase 3 study, the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline at the approved dose were lower than those seen with patients treated with imipenem and cilastatin (imipenem/cilastatin). We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia. This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia. Subjects with hospital-acquired pneumonia were randomized to receive one of two doses of tigecycline (150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection, depending on the randomization regimen. Clinical response, defined as cure, failure of treatment, or indeterminate outcome, was assessed 10 to 21 days after the last day of therapy. In the clinically evaluable population, clinical cure with tigecycline 100 mg (17/20, 85.0%) was numerically higher than with tigecycline 75 mg (16/23, 69.6%) and imipenem/cilastatin (18/24, 75.0%). No new safety signals with the high-dose tigecycline were identified. A numerically higher clinical response was observed with the 100-mg dose of tigecycline. This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia. Further studies are necessary. (The ClinicalTrials.gov identifier for this clinical trial is NCT00707239.)

Promoting quality mentorship of undergraduate science students has recently emerged as an important strategy for successfully recruiting and retaining students in the sciences. Although numerous faculty members are naturally gifted mentors, most faculty are inserted into a mentorship role with little, if any, training. Successfully mentoring undergraduate science students requires a myriad of skills that can be honed with forethought and practice. In this essay, the value of mentoring, the developmental profile of young adult students, and the traits of a good mentor are explored. The Triangular Model proposed by W. Brad Johnson provides a theoretical framework for the development of effective mentorship. Fifteen tips gleaned from the literature and the author’s personal experience are provided to help improve mentoring skills of faculty working with undergraduate science students.

High-speed video imaging was used to study the dynamic behavior of cavitation bubbles induced by a continuous wave (CW) laser into highly absorbing droplets water containing copper nitrate (CuNO 4 ). The droplet lays horizontally on a glass surface and the laser beam (λ=975 nm) propagates vertically from underneath, across the glass and into the droplet. This beam is focused ζ=400 μm above the glass-liquid interface in order to produce the largest bubble as possible (R max ~ 1mm). In our experiment the thermocavitation bubbles are always in contact with the substrate, taking a hemispherical shape, regardless of where the laser focal point is, as opposed to the other methods that involved nano and picosecond laser pulses, where bubbles may nucleate and grow within the bulk of the fluid. We focus on the liquid jet which emerges out the droplet at velocities of about 3 m/s, due to the acoustic pressure wave (APW) emitted immediately after the bubble collapse, and after it breaks up into a secondary droplet or droplets depending of the droplet’s volume, showing an alternative way of droplet generator that is simplest, light and cheaper. The dynamics of cavitation bubbles in confined geometries (drops) offers a rich hydrodynamic and the liquid jet generated after the bubble collapse could be used like acoustic waveguide, as was showed by Nicolas Bertin et. al.

Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Several investigators recently reported an increased risk of cardiovascular events (CVEs) in hospitalized patients with community-acquired pneumonia (CAP). CVEs may be the primary determinant of clinical failure in hospitalized patients with CAP. Future research may be necessary to identify patients at risk of CVEs during or after an episode of CAP. In these patients, therapeutics beyond antibiotics (eg, heparin or aspirin) may be indicated during and after hospitalization.

This case report shows a striking correlation of remarkable brief high levels of pro- and anti-inflammatory cytokines coupled with increased neutrophil activation, followed by a sharp decrease in cytokine levels and increased neutrophil apoptosis associated with the favorable clinical outcomes of a patient with severe influenza infection. The host response examined in our case is not complete, given it did not assess the full spectrum of host response. The brief neutrophil and cytokine response seen in our case in the absence of antiviral therapy and in the presence of methotrexate immunosuppressive therapy rise the question as to whether the latter optimally modulated the macrophage function, resulting in a favorable outcome of severe influenza viral infection.

a b s t r a c t Objective: To analyze the frequency and characteristics of dose reduction of biological agents in a cohort of patients with chronic arthritis, in clinical practice conditions in a tertiary level hospital. Materials and methods: Descriptive, cross-sectional study, which included all patients, followed consecutively during 6 months (June 2011–November 2011), by one investigator, with patients who at least have received one dose of biological agents in 2011. Results: We included 153 patients: rheumatoid arthritis (RA) (n=82), ankylosing spondylitis (n=29), psoriatic arthritis (n=20), and miscellaneous group (n=22). Mean disease duration was 14.9±7.7 years. At the time of analysis, 70 patients (45.7%) were receiving low doses of biological therapy (50% in miscellaneous group group, 50% in psoriatic arthritis, 48.2% in ankylosing spondylitis, and 42.6% in RA). Mean time of dosage reduction was 17.4±17.5 months. The most common biological agents used in low dose were: etanercept, adalimumab and tocilizumab in 57.6%, 54.9%, and 40% respectively, in patients with a reduced dose of biological therapy. The patients at low dose of biological therapy compared with standard dose had similar mean disease duration, but received significantly less DMARDs, glucocorticoids and NSAIDs, and similar biological agent duration. RA patients with reduced biological treatment, at the time of analysis, had higher remission rates versus patients receiving a standard dose (82.9% vs 34%, P

In this issue of the European Respiratory Journal , Engel et al. [1] studied barriers for early switch therapy in hospitalised patients with community-acquired pneumonia (CAP). The authors reference our initial work in the field of switch therapy, published in 1995 in Archives of Internal Medicine [2]. In hospitalised patients with CAP, the standard of practice before 1995 was to use intravenous antibiotics for the full duration of therapy. During our initial study, we obtained consent from patients to see if they were willing to participate in a trial using oral antibiotics once they reached clinical stability. Our Institutional Review Board requested a full evaluation of the initial 10 patients enrolled in the trial to be sure that a switch to oral antibiotics would not be associated with poor clinical outcomes. During the development of the protocol we decided to define clinical stability using two symptoms of CAP (cough and sputum production) and two signs of systemic response (fever and leukocytosis). Patients were defined as …

Introduction Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum. Methods A cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as 'ACPA negative' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array. Results A total of 83 patients underwent arthroscopy, with a mean age of 55.9 ± 12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1β, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients. Conclusions In our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology., This study was supported by a public grant from Fondo de Investigación Sanitaria (FIS: PI 080207) of the Ministerio de Sanidad y Consumo, Instituto Carlos III, Spain).

Chlamydia pneumoniae has recently been associated with atherosclerotic lesions in coronary arteries. To investigate the biological basis for the dissemination and proliferation of this organism in such lesions, the in vitro growth of C. pneumoniae was studied in two macrophage cell lines, peripheral blood monocyte-derived macrophages, human bronchoalveolar lavage macrophages, several endothelial cell lines, and aortic smooth muscle cells. Five strains of C. pneumoniae were capable of three passages in human U937 macrophages and in murine RAW 246.7 macrophages. Titers were suppressed in both macrophage types with each passage, as compared with growth titers in HEp-2 cells. Both human bronchoalveolar lavage macrophages and peripheral blood monocyte-derived macrophages were able to inhibit C. pneumoniae after 96 h of growth. Eleven C. pneumoniae strains were capable of replicating in normal human aortic artery-derived endothelial cells, umbilical vein-derived endothelial cells, and pulmonary artery endothelial cells. Infection in human aortic artery smooth muscle cells was also established for 13 strains of C. pneumoniae. The in vitro ability of C. pneumoniae to maintain infections in macrophages, endothelial cells, and aortic smooth muscle cells may provide support for the hypothesis that C. pneumoniae can infect such cells and, when infection is followed by an immune response, may contribute to atheroma formation in vivo. More studies are needed to investigate the complex relationship between lytic infection and persistence and the potential for C. pneumoniae to influence the generation of atheromatous lesions.

Six stay-in-place precast, prestressed deck panels were tested to evaluate the horizontal shear strength between the precast panel and the cast-in-place portion of the bridge deck. Presently, the Indiana Department of Transportation requires a minimum of 20 shear connectors regardless of panel dimensions. The shear connectors are placed across a broom finished deck panel surface. Broom finish with approximately 0.05 to 0.075 in. (1.27 to 1.91 mm) total amplitude deformations is specified instead of a raked finish with 0,25 in. (6.35 mm) total amplitude because of the reduced 2.5 in. (63.5 mm) thickness of the panels used in Indiana. In this study, composite behavior at ultimate, including horizontal shear and interface slip characteristics, was evaluated. It is concluded that stay-in-place precast, prestressed deck panels with a broom finished surface do not require horizontal shear connectors if the nominal average horizontal shear stress at the interface is less than 116 psi (0.8 MPa).

It has been suggested that in hospitalized patients with pneumonia intravenous antimicrobials can be switched to oral antimicrobials when the patient shows evidence of clinical improvement. At the University of Louisville and the Veterans Affairs Medical Center of Louisville, we have performed several prospective studies to evaluate the clinical outcome of patients treated with short courses of intravenous antimicrobials with an early switch to oral antimicrobials (called “switch therapy”). Patients are switched to oral antimicrobials when (1) cough and respiratory distress are improving, (2) the patient is afebrile for at least 8 hours, (3) the white blood cell count is returning toward normal, and (4) there is no evidence of abnormal gastrointestinal absorption. Combining our prospective clinical studies, we have patient outcome data from more than 150 patients with community-acquired pneumonia and 20 patients with nosocomial pneumonia who were treated with switch therapy. The clinical cure rate was 99%. Since the implementation of switch therapy in 1991, we were able to decrease mortality and length of hospital stay for hospitalized patients with pneumonia in our institution. The mortality rate for patients with pneumonia decreased from 13.3% in 1990 to 8.6% in 1993. The length of hospitalization for patients with pneumonia decreased from 8.2 days in 1990 to 5.8 days in 1993. Based on our clinical experience, we consider switch therapy to be a safe and cost-effective treatment modality for hospitalized patients with pneumonia. Switch therapy may be considered as one of the primary options for containment of health care costs in the management of pneumonia.

The entorhinal cortex participates in a variety of spatial and locomotor behaviors that are thought to be mediated by the hippocampal formation. The present study examined the possibility that the entorhinal area contributes to the maintenance of an operant behavior in which the hippocampus is also implicated—differential reinforcement of low-rate responding (DRL). Rats with bilateral entorhinal cortex lesions or sham operations were tested for retention of a preoperatively learned DRL (10-sec delay) task. Rats with entorhinal lesions were impaired on measures of response rate, temporal discrimination, and response efficiency for 2 to 3 weeks after surgery. Histological analyses indicated that all the rats sustained complete entorhinal lesions. The entorhinal cortex may be an important component of the hippocampal formation contributing to the performance of DRL tasks.

Community acceptance and participation are essential for the success of mass ivermectin chemotherapy programmes for onchocerciasis (river blindness). To explore the local understanding of the purpose of ivermectin and willingness to continue taking the drug, we performed questionnaire surveys in four communities with hyperendemic onchocerciasis after each of three ivermectin treatment rounds. More than 100 respondents participated in each KAP survey, representing the heads of 30% of the households in each community. The respondents rarely stated that the goal of the ivermectin treatment programme was to prevent visual loss. Instead, they said they were taking the drug for their general well-being, to cure the onchocercal nodule (filaria), or to cure the microfilaria, a term newly introduced by agents of the treatment programme. The principal reason identified for refusal to take ivermectin was anxiety about drug-related adverse reactions, and there were marked differences between communities in acceptance of treatment. In one community over 50% of residents initially refused to take ivermectin, although participation rates improved somewhat after programmatic adjustments. We recommend that ivermectin distribution programmes establish surveillance activities to detect where acceptance is poor, so that timely and community-specific adjustments may be devised to improve participation.

The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) suggested two sets of criteria in 2001 and 2007 to define clinical stability in community-acquired pneumonia (CAP). The present study aimed to evaluate the level of agreement between these two sets of criteria and how well they can predict clinical outcomes. A retrospective cohort study was carried out of 487 consecutive patients hospitalised with CAP. Level of agreement was tested using a survival curve analysis, while prediction of outcomes at 30-day follow-up was evaluated through receiver operating characteristic (ROC) analysis. A discrepancy between ATS 2001 and ATS/IDSA 2007 criteria in identifying clinical stability was detected in 62% of the patients. The median (interquartile range) time to clinical stability was 2 (1–4) days based on ATS 2001 and 3 (2–5) days based on ATS/IDSA 2007 criteria (p = 0.012). The daily distribution of patients who reached clinical stability evaluated with both sets was different (p = 0.002). The ROC analysis showed an area under the curve of 0.705 for the ATS 2001 criteria and 0.714 for ATS/IDSA 2007 criteria (p = 0.645). ATS 2001 and ATS/IDSA 2007 criteria for clinical stability in hospitalised patients with CAP are clinically equivalent and both can be used in clinical practice as well as in clinical research.

SummaryObjectiveTo compare demographic and clinical characteristics, and methicillin-resistant Staphylococcus aureus (MRSA) strain characteristics, in patients with early-onset (EO) and late-onset (LO) MRSA nosocomial pneumonia.MethodsThis was a retrospective analysis of data from a multicenter observational study of nosocomial pneumonia patients admitted between November 2008 and July 2010. Laboratory analyses performed on MRSA isolates included confirmation of antimicrobial susceptibility and heteroresistance to vancomycin, USA typing, staphylococcal cassette chromosome (SCC) mec typing, and detection of Panton–Valentine leukocidin (PVL) genes.ResultsWe identified 134 patients; 42 (31%) had EO MRSA pneumonia and 92 (69%) had LO MRSA pneumonia. The patients in the LO group were more likely to have risk factors for multidrug-resistant pathogens (98% vs. 76%, p

Optodielectrophoresis has been shown to be an interesting tool for massive manipulation of microparticles using external electric fields. Here, no electrode fabrication is need it since they are created by the light distribution incident onto a photoconducting material. We propose the use of this device for the recording of dynamic holograms in hydrogenated amorphous silicon (a:Si-H)-liquid crystals hybrid devices. The device consists of 5CB liquid crystal sandwiched between a photoconductive a:Si-H substrate and an ITO covered glass-plate. Diffraction efficiency of 3.3% is obtained when holograms are recorded with a low power He-Ne laser.

Trapping with evanescent fields has become an important tool in many research fields. Evanescent fields allow trapping of particles in close proximity to a surface. However, excitation of these waves may be cumbersome. Recently, trapping with photorefractive electric fields has been demonstrated using dielectric and metallic nano and microparticles. Excitation of these fields is straight forward and, in principle, can be excited with microwatt power level. In this work, we give a comparison of photorefractive and plasmonic trapping emphasizing its advantages and disadvantages. We show that single beam and holographic photorefractive photovoltaic trapping in LiNbO 3 of microparticle in water is possible.

Background Healthcare-associated infections are a major source of morbidity and mortality in the United States. Infection Preventionists (IPs) are healthcare workers tasked at overseeing the prevention and control of these infections, but they may have difficulties obtaining up-to-date information, primarily in rural states. The objective of this study was to evaluate the importance of public health involvement on the knowledge-sharing network of IPs in a rural state. Findings A total of 95 attendees completed our survey. The addition of public health professionals increased the density of the network, reduced the number of separate components of the network, and reduced the number of key players needed to contact nearly all of the other network members. All network metrics were higher for public health professionals than for IPs without public health involvement. Conclusions The addition of public health professionals involved in healthcare infection prevention activities augmented the knowledge sharing potential of the IPs in Iowa. Rural states without public health involvement in healthcare-associated infection (HAI) prevention efforts should consider the potential benefits of adding these personnel to the public health workforce to help facilitate communication of HAI-related information.

Lower respiratory tract infections are the most common infectious cause of death in the world and the third most common cause of death globally (all causes). This article reviews the epidemiology of community-acquired pneumonia from a global perspective. Major areas of epidemiological work include (1) disease surveillance to define the burden of disease and to document outbreaks, (2) identification of risk factors for a disease to optimize prevention strategies, and (3) comparisons of treatment effects to improve clinical outcomes for patients with the disease.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial pneumonia. To characterize pathogen-derived and host-related factors in intensive care unit (ICU) patients with MRSA pneumonia, we evaluated the Improving Medicine through Pathway Assessment of Critical Therapy in Hospital-Acquired Pneumonia (IMPACT-HAP) database. We performed multivariate regression analyses of 28-day mortality and clinical response using univariate analysis variables at a P level of mec types II (64.1%) and IV (33.1%), and agr I (36.7%) and II (61.8%). Panton-Valentine leukocidin (PVL) was present in 21.9%, and vancomycin heteroresistance was present in 15.9%. Mortality occurred in 37.1% of patients; factors in the univariate analysis were age, APACHE II score, AIDS, cardiac disease, vascular disease, diabetes, SCC mec type II, PVL negativity, and higher vancomycin MIC (all P values were P < 0.001) and age (OR, 1.024; 95% CI, 1.003 to 1.046; P = 0.02). Clinical failure occurred in 36.8% of 201 evaluable patients; the only independent predictor was APACHE II score (OR, 1.082; 95% CI, 1.031 to 1.136; P = 0.002). In summary, APACHE II score (mortality, clinical failure) and age (mortality) were the only independent predictors, which is consistent with severity of illness in ICU patients with MRSA pneumonia. Interestingly, our univariate findings suggest that both pathogen and host factors influence outcomes. As the epidemiology of MRSA pneumonia continues to evolve, both pathogen- and host-related factors should be considered when describing epidemiological trends and outcomes of therapeutic interventions.

Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.

Although for some highly lipophillic drugs the principal barrier to permeate the human skin may reside in the essentially viable epidermal membrane, for most molecules, the stratum corneum (SC) is the rate-limiting barrier to drug delivery. Today, several techniques have been developed to enhance transdermal drug delivery (TDD) by increasing the effective permeability of the SC (e.g., iontophoresis, electroporation, micro-needle, ultrasound, radio frequency and laser radiation). The goal of this study is to investigate the extent to which thermocavitation may be used as a novel alternative method to selectively pierce the SC and thus enhance TDD. Thermocavitation for this purpose is generated by a continuous wave (CW), low power laser beam focused on a highly-absorbing solution topically applied on the skin surface. The absorbed light creates a superheated volume in a tightly localized region followed by explosive phase transition and the formation of vapor-gas bubbles, which expand and later collapse very rapidly emitting intense acoustic shockwaves that disrupt the surface underneath.Thermocavitation bubbles were induced close to the surface of skin models (agar gels) andThe damage observed on agar gel and porcine skin appears to be congruent with the relationship between laser power, focal point, cavitation frequency and extent of damage observed in previous studies. In particular, the greatest damage induced to the agar phantoms was produced with the lowest laser power (∼153 mW) and thinnest solution layer (∼100 μm) used. Similar laser and solution layer settings led to porcine skin damage of ∼80–100 μm in diameter, which was sufficiently large to break the SC and allow the penetration of 4 kDa, FITC-dextran to depths of ∼40–60 μm.This novel approach to achieve cavitation is attractive and seems promising because it can be generated with inexpensive, low power CW lasers, capable of selectively disrupting the SC and allowing the penetration of large, hydrophilic drugs topically applied to the skin.

A multicentre prospective randomised open-label controlled trial was conducted to compare the efficacy and safety of aztreonam (1 to 2g every 8 hours) plus cefazolin (1g every 8 hours) with that of ceftazidime (1 to 2g every 8 hours) in patients with nosocomial pneumonia. 66 adults were enrolled who had a presumptive diagnosis of pneumonia made at least 48 hours after hospitalisation. Patients exhibited the classic clinical picture of pneumonia and/or fever and/or leucocytosis and a newly developed or expanding infiltrate on chest x-ray. Among 48 evaluable patients treated, clinical cure or improvement was reported in 18 of 20 (90%) aztreonam patients as compared with 24 of 28 (85.7%) patients treated with ceftazidime. Bacteriological eradication or presumptive eradication was reported in 11 of 13 (84.6%) aztreonam patients and 15 of 19 (78.9%) ceftazidime recipients. Five patients with positive blood cultures prior to therapy (2 aztreonam, 3 ceftazidime) had negative blood cultures at study completion. Superinfection was reported in 2 patients randomised to aztreonam (both Staphylococcus aureus) and in 3 ceftazidime patients (2 with Pseudomonas aeruginosa and 1 with β-haemolytic Streptococcus). Colonisation was observed following ceftazidime (n = 4) and aztreonam (n = 2) therapy. Six aztreonam and 3 ceftazidime recipients experienced adverse events, which were possibly related to study therapy. Aztreonam plus cefazolin appears to be as effective as ceftazidime for the treatment of adults with nosocomial pneumonia.

New strategies for improving antimicrobial therapy have two primary objectives: improve patient outcome and decrease health care costs. According to the clinical situation, therapeutic use of antimicrobials can be classified as "empiric therapy," "known pathogen therapy," or "switch therapy." In "switch therapy" there is an early transition from intravenous to oral antimicrobial agents to complete the total course of therapy. We have developed a series of criteria for such a transition. If these criteria are met, switch therapy can be safely applied to pulmonary, skin and soft tissue, urinary, and intraabdominal infections. Oral agent selection for switch therapy should be based on appropriate pharmacokinetics and microbiologic activity of the oral agent. We have also compared the economic efficiency of switch therapy in patients hospitalized with community-acquired pneumonia with historical controls in patients treated with conventional intravenous therapy. Overall results indicate that switch therapy offers a safe and effective means of decreasing the duration of intravenous therapy and hospitalization. It also appears to reduce health care costs while maintaining a high standard of patient care.

Air conditioner condensates have not been previously associated with cases of Legionnaires' disease. We report the possible transmission of Legionella pneumophila serogroup 1 from a malfunctioning automobile air conditioning system's leaking water onto the floorboard of a car driven for a long distance by the patient. Heteroduplex analysis of polymerase chain reaction products was used to help establish an epidemiologic link between the water specimen and the patient.

Background The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care–associated (HCAP) pneumonia. Objective The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. Methods This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. Results Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9–13.9]; P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09–6.54]; P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02–1.23]; P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough 20 mg/L ( P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels 20 mg/L (Kaplan-Meier analysis, P = 0.0003). Conclusions Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.