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Metabolic syndrome (MS) is a combination of risk factors related to the development of mainly type 2 diabetes mellitus, cardiovascular disease (CVD) and nonalcoholic fatty liver disease (NAFLD). Its prevalence has increased worldwide, and healthcare systems will face major challenges in addressing this problem. The aim of this work was to evaluate the effect of hyperbaric oxygen therapy (HBOT) on insulin resistance (IR) and obesity associated with MS in Wistar rats. The experimental design consisted of three groups of sucrose-induced MS rats: the MS group that consumed sucrose (MS-Suc; n=5), the MS group that ingested sucrose and HBOT (MS-Suc-HBOT; n=5), the MS group that did not consume sucrose and that received HBOT (MS-HBOT; n=5) and the control group. The rats received HBOT for 20 d at 2.4 atmospheres absolute (ATA) for 60 min. Subsequently, the rats were euthanized, and body fat weight, serum biochemical parameters and microscopic analysis of adipose tissue were determined. Rats with hyperoxia had decreased body weight, adipose tissue hypertrophy, and abdominal and epididymal fat. Likewise, markers of insulin resistance (glucose, insulin and HOMA-IR), biochemical parameters of dyslipidemia (cholesterol and triglycerides) and nonalcoholic fatty liver (AST and ALT) decreased; in contrast, compared to the control group, HBOT increased the 1/HOMA-IR, HOMA-βCell and McAuley indexes, which were related to the improvement in insulin sensitivity (p

As the seismic hazard has been updated for the central U.S., state Departments of Transportation (DOTs) find an increasing need to assess the seismic vulnerability of their bridge network. Traditional methods to perform seismic assessment require developing dynamic models for each bridge. However, this approach requires specialized engineering knowledge and information from structural drawings, and is time-consuming. To streamline this important task, a simplified dynamic modeling procedure is described that leverages readily available information from DOTs’ asset management databases. With a minimal amount of additional data items, the asset management database can be used to identify vulnerable bridges rapidly and with sufficient accuracy for the prioritization of retrofit decisions. A detailed analysis of a 100-bridge sample set identified typical vulnerabilities and established corresponding capacity thresholds. The rapid seismic vulnerability assessment methodology is implemented as an Excel macro-enabled tool for bridge owners and asset managers to rapidly assess the vulnerability of each individual bridge based on current information in the database, and then classify the vulnerability of each individual bridge as low, medium, or high. Current DOT databases used for asset management in regions of low-to-moderate seismicity do require some data items be added for a robust assessment. These data items are identified here and leveraged to demonstrate the method. The rapid assessment methodology presented can be implemented to effectively identify the most vulnerable bridges in a bridge network, thus facilitating a rapid state bridge inventory network assessment to prioritize and inform actions such as maintenance and rehabilitation.

BACKGROUND: Although targeted biological treatments have transformed the outlook for patients with rheumatoid arthritis, 40% of patients show poor clinical response, which is mechanistically still unexplained. Because more than 50% of patients with rheumatoid arthritis have low or absent CD20 B cells-the target for rituximab-in the main disease tissue (joint synovium), we hypothesised that, in these patients, the IL-6 receptor inhibitor tocilizumab would be more effective. The aim of this trial was to compare the effect of tocilizumab with rituximab in patients with rheumatoid arthritis who had an inadequate response to anti-tumour necrosis factor (TNF) stratified for synovial B-cell status. METHODS: This study was a 48-week, biopsy-driven, multicentre, open-label, phase 4 randomised controlled trial (rituximab vs tocilizumab in anti-TNF inadequate responder patients with rheumatoid arthritis; R4RA) done in 19 centres across five European countries (the UK, Belgium, Italy, Portugal, and Spain). Patients aged 18 years or older who fulfilled the 2010 American College of Rheumatology and European League Against Rheumatism classification criteria for rheumatoid arthritis and were eligible for treatment with rituximab therapy according to UK National Institute for Health and Care Excellence guidelines were eligible for inclusion in the trial. To inform balanced stratification, following a baseline synovial biopsy, patients were classified histologically as B-cell poor or rich. Patients were then randomly assigned (1:1) centrally in block sizes of six and four to receive two 1000 mg rituximab infusions at an interval of 2 weeks (rituximab group) or 8 mg/kg tocilizumab infusions at 4-week intervals (tocilizumab group). To enhance the accuracy of the stratification of B-cell poor and B-cell rich patients, baseline synovial biopsies from all participants were subjected to RNA sequencing and reclassified by B-cell molecular signature. The study was powered to test the superiority of tocilizumab over rituximab in the B-cell poor population at 16 weeks. The primary endpoint was defined as a 50% improvement in Clinical Disease Activity Index (CDAI50%) from baseline. The trial is registered on the ISRCTN database, ISRCTN97443826, and EudraCT, 2012-002535-28. FINDINGS: Between Feb 28, 2013, and Jan 17, 2019, 164 patients were classified histologically and were randomly assigned to the rituximab group (83 [51%]) or the tocilizumab group (81 [49%]). In patients histologically classified as B-cell poor, there was no statistically significant difference in CDAI50% between the rituximab group (17 [45%] of 38 patients) and the tocilizumab group (23 [56%] of 41 patients; difference 11% [95% CI -11 to 33], p=0·31). However, in the synovial biopsies classified as B-cell poor with RNA sequencing the tocilizumab group had a significantly higher response rate compared with the rituximab group for CDAI50% (rituximab group 12 [36%] of 33 patients vs tocilizumab group 20 [63%] of 32 patients; difference 26% [2 to 50], p=0·035). Occurrence of adverse events (rituximab group 76 [70%] of 108 patients vs tocilizumab group 94 [80%] of 117 patients; difference 10% [-1 to 21) and serious adverse events (rituximab group 8 [7%] of 108 vs tocilizumab group 12 [10%] of 117; difference 3% [-5 to 10]) were not significantly different between treatment groups. INTERPRETATION: The results suggest that RNA sequencing-based stratification of rheumatoid arthritis synovial tissue showed stronger associations with clinical responses compared with histopathological classification. Additionally, for patients with low or absent B-cell lineage expression signature in synovial tissue tocilizumab is more effective than rituximab. Replication of the results and validation of the RNA sequencing-based classification in independent cohorts is required before making treatment recommendations for clinical practice. FUNDING: Efficacy and Mechanism Evaluation programme from the UK National Institute for Health Research. ispartof: LANCET vol:397 issue:10271 pages:305-317 ispartof: location:England status: published

Background: The potential association of the ABO blood group with the risk of COVID-19 and its severity has attracted a lot of interest since the start of the pandemic. While a number of studies have reported an increased risk associated with blood type A and a reduced risk with type O, other studies have did not found a significant effect. This study aimed to define the prevalence of different ABO blood groups in hospitalized COVID-19 patients in the Louisville, KY area and to investigate whether an association exists between the blood group and disease severity. Methods: This was a retrospective observational study of 380 patients with SARS-CoV-2 infection hospitalized to eight of the adult hospitals in the city of Louisville. Patients were divided into four different groups according to their ABO blood type. Demographic characteristics and clinical variables, including laboratory data as well as clinical outcomes were compared. Results: Type O was the most common blood group among the hospitalized patients (51%) followed by type A (31%), B (14%) and AB (4%). The observed blood group distribution among the patients was not significantly different from the distribution expected when compared to a population of similar racial/ethnic composition. No significant associations were found between the blood group and comorbidities, inflammatory biomarkers as well as with recorded outcomes, including the mortality rate and the length of the hospital stay. Conclusions: The data from hospitalized patients in Louisville is is not consistent with the ABO blood group having a significant effect as a risk or severity factor for COVID-19, but it is representative in COVID-19 or its severity of its prevalence among different racial/ethnic populations.

Load distribution factor for truck loads is a key parameter in evaluating the load-carrying capacity of existing bridges. This study aimed to investigate load rating procedures for reinfor...

We present 3D steady-state trapping and manipulation of vapor microbubbles in pure ethanol by optothermal effects induced by low power CW laser. Light absorption from silver nanoparticles photodeposited on the core of a multi-mode optical fiber is used as a heat source to induce microbubbles of several diameters. The optothermal effects generated by the light absorption of light bulk absorption modulates the microbubble wall's surface tension inducing both longitudinal and transversal forces just like optical forces, generating a 3D potential well. By numerical simulations, we find expressions to describe both the temperature profiles and the convective currents. Besides, using an array of three optical fibers with silver nanoparticles photodeposited on their cores we show the transmission of microbubbles from one fiber to another by switching the laser radiation from the CW lasers.

Chronic obstructive pulmonary disease (COPD) is prevalent in patients infected with HIV. The purpose of this study was to test the hypothesis that systemic oxidation correlates with loss of lung function in subjects with COPD, and that HIV infection can contribute to creating such an environment. Subjects were recruited at the University of Louisville in the following groups: HIV-infected (n = 36), COPD (n = 32), HIV and COPD (n = 28), and uninfected controls with normal lung function (n = 34). HIV infection was assessed by viral load and CD4 cell counts. Pulmonary function was determined by spirometry, and plasma was collected for measurement of cysteine (Cys), cystine (CySS), glutathione (GSH) and GSH disulfide (GSSG) by HPLC followed by estimation of redox potentials (Eh) using the Nernst equation. Results showed that patients with COPD had more oxidized plasma Eh Cys/CySS than patients with normal lung function, but plasma Eh GSH/GSSG was unaltered. In addition, there was a correlation between the extent of plasma Eh Cys/CySS oxidation and loss of lung function, and this correlation remained even after correcting for age, sex, race and body mass index. HIV infection per se was not associated with increased oxidation of plasma Eh Cys/CySS, but plasma Eh Cys/CySS was more oxidized in patients with lower CD4-positve T cell counts. In patients with both HIV infection and COPD, there was a significant correlation between CD4 cell counts and lung function. Thus, systemic oxidation correlated with decreased lung function in subjects with COPD and decreased CD4 counts in subjects infected with HIV. Thus, factors contributing to plasma Eh Cys/CySS may represent novel mechanisms underlying the increased prevalence of COPD in people living with HIV.

espanolAims To describe the methodology of REAPSER (Spanish Registry of Recent-onset Psoriatic Arthritis), its strengths and limitations. The aim of this study is to identify prognostic factors for the clinical and radiographic course in a cohort of patients with psoriatic arthritis (PsA) diagnosed within 2 years of symptom evolution. Methods Multicenter, observational and prospective study (with 2-year follow-up including annual visits). Baseline visit intended to reflect patient situation before the disease course was modified by treatments prescribed in rheumatology departments. Patients were invited to participate consecutively in one of their routine visits to the rheumatologist. 211 patients were included. Following data were collected: sociodemographic variables; employment situation; family history; personal history and comorbidities; anthropometric data; lifestyle; use of healthcare services; clinical situation at the time of PsA diagnosis; joint involvement and spinal pain; pain and overall assessment; enthesitis, dactylitis and uveitis; skin and nail involvement; functional situation and quality of life; radiographic evaluation; analytical determinations; treatment; axial and peripheral flare-ups. Conclusions The REAPSER study includes a cohort of patients with recent-onset PsA, before the disease course was modified by disease-modifying antirheumatic drugs prescribed in rheumatology departments. Exhaustive information collected in each visit is expected to be an important data source for future analysis. espanolObjetivos Describir la metodologia del Registro Espanol de Artritis Psoriasica de reciente comienzo de la Sociedad Espanola de Reumatologia (REAPSER), asi como sus fortalezas y limitaciones. El objetivo principal del proyecto es identificar factores pronosticos de la evolucion clinica y radiografica en una cohorte de pacientes que padecen artritis psoriasica (APs) diagnosticada con menos de 2 anos de evolucion. Material y metodo Estudio observacional, prospectivo (2 anos de seguimiento; periodicidad anual de las visitas), multicentrico. La intencion en la visita basal fue reflejar la situacion del paciente antes de que la evolucion de la enfermedad se viese modificada por los tratamientos pautados en los servicios de reumatologia. Los pacientes fueron invitados a participar consecutivamente en una de sus visitas habituales al reumatologo. El tamano muestral finalmente alcanzado fue de 211 pacientes. Se recogen datos sociodemograficos; de situacion laboral; historia familiar; antecedentes personales y comorbilidad; antropometricos; estilo de vida; uso de los servicios de salud; situacion clinica al diagnostico de APs; afectacion articular y dolor espinal; dolor y valoracion global de la enfermedad; entesitis, dactilitis y uveitis; afectacion cutanea y ungueal; situacion funcional y calidad de vida; evaluacion radiografica; determinaciones analiticas; tratamiento; brotes en esqueleto axial y periferico. Conclusiones El estudio REAPSER incluye una cohorte de pacientes con APs de inicio reciente reclutados antes de que la evolucion de la enfermedad se viese modificada por la prescripcion de FAME en los servicios de reumatologia. Se espera que la informacion exhaustiva recogida en las visitas suponga una amplia fuente de datos para futuros analisis.

Background Multiple criteria have been proposed to define community-acquired pneumonia (CAP) severity and predict ICU admission. Validity studies have found differing results. We tested four models to assess severe CAP built upon the criteria included in the 2007 IDSA/ATS guidelines, hypothesizing that a model providing different weights for each individual criterion may be of better predictability. Methods Retrospective analysis of a prospective cohort study of adult hospitalizations for CAP at nine hospitals in Louisville, KY from June 2014 to May 2016. Four models were tested. Model 1: original 2007 IDSA/ATS criteria. Model 2: modified IDSA/ATS criteria by removing multilobar infiltrates and changing BUN threshold to ≥30 mg/dL; adding lactate level >2 mmol/L and requirement of non-invasive mechanical ventilation (NIMV). CAP was severe with 1 major criterion or 3 minor criteria. Model 3: same criteria as model 2, CAP was severe with 1 major criterion or 4 minor criteria. Model 4: multiple regression analysis including the modified criteria as described in models 2 and 3 with a score assigned to each variable according to the magnitude of association between variable and need for ICU. Results 8284 CAP hospitalizations were included. 1458 (18%) required ICU. Model 4 showed highest prediction of need for ICU with an area under the curve of 0.91, highest accuracy, specificity, positive predictive value, and agreement among models. Conclusion Assigning differential weights to clinical predictive variables generated a score with accuracy that outperformed the original 2007 IDSA/ATS criteria for severe CAP and ICU admission.

Background Few studies have measured the burden of adult pneumococcal disease after the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the US infant vaccination schedule. Further, most data regarding pneumococcal serotypes are derived from invasive pneumococcal disease (IPD), which represents only a fraction of all adult pneumococcal disease burden. Understanding which pneumococcal serotypes cause pneumonia in adults is critical for informing current immunization policy. The objective of this study was to measure the proportion of radiographically-confirmed (CXR+) community-acquired pneumonia (CAP) caused by PCV13 serotypes in hospitalized US adults. Methods This observational, prospective surveillance study recruited hospitalized adults aged ≥18 years from 21 acute care hospitals across 10 geographically-dispersed cities in the United States between October 2013 and September 2016. Clinical and demographic data were collected during hospitalization. Vital status was ascertained 30 days after enrollment. Pneumococcal serotypes were detected via culture from the respiratory tract and normally-sterile sites (including blood and pleural fluid). Additionally, a novel, Luminex-based serotype-specific urinary antigen detection (UAD) assay was used to detect serotypes included in PCV13. Results Of 15,572 enrolled participants, 12,055 eligible patients with CXR+CAP were included in the final analysis population. Mean age was 64.1 years and 52.7% were aged ≥65 years. Common comorbidities included chronic obstructive pulmonary disease (43.0%) and diabetes mellitus (28.6%). PCV13 serotypes were detected in 552/12,055 (4.6%) of all patients and 265/6347 (4.2%) of those aged ≥65 years. Among patients aged 18–64 years PCV13 serotypes were detected in 3.8–5.3% of patients depending on their risk status. Conclusions After implementation of a pneumococcal conjugate vaccination program in US children, and despite the herd protection observed in US adults, a persistent burden of PCV13-type CAP remains in this population.

Background Recruitment manoeuvres generate a transient increase in trans-pulmonary pressure that could open collapsed alveoli. Recruitment manoeuvres might generate very high inspiratory airflows. We evaluated whether recruitment manoeuvres could displace respiratory secretions towards the distal airways and impair gas exchange in a porcine model of bacterial pneumonia. Methods We conducted a prospective randomised study in 10 mechanically ventilated pigs. Pneumonia was produced by direct intra-bronchial introduction of Pseudomonas aeruginosa. Four recruitment manoeuvres were applied randomly: extended sigh (ES), maximal recruitment strategy (MRS), sudden increase in driving pressure and PEEP (SI-PEEP), and sustained inflation (SI). Mucus transport was assessed by fluoroscopic tracking of radiopaque disks before and during each recruitment manoeuvre. The effects of each RM on gas exchange were assessed 15 min after the intervention. Results Before recruitment manoeuvres, mucus always cleared towards the glottis. Conversely, mucus was displaced towards the distal airways in 28.6% ES applications and 50% of all other recruitment manoeuvres (P=0.053). Median mucus velocity was 1.26 mm min−1 [0.48–3.89] before each recruitment manoeuvre, but was reversed (P=0.007) during ES [0.10 mm min−1 [-0.04–1.00]], MRS [0.10 mm min−1 [-0.4–0.48]], SI-PEEP [0.02 mm min−1 [-0.14–0.34]], and SI [0.10 mm min−1 [-0.63–0.75]]. When PaO2 failed to improve after recruitment manoeuvre, mucus was displaced towards the distal airways in 68.7% of the cases, compared with 31.2% recruitment manoeuvres associated with improved PaO2 (odds ratio: 4.76 (95% confidence interval: 1.13–19.97). Conclusions Recruitment manoeuvres dislodge mucus distally, irrespective of airflow generated by different recruitment manoeuvres. Further investigation in humans is warranted to corroborate these pre clinical findings, as there may be limited benefits associated with lung recruitment in pneumonia.

Background and AimsGM-CSF-dependent macrophage polarization has been demonstrated in rheumatoid arthritis (RA). Our aim was to seek diagnostic/prognostic biomarkers for undifferentiated arthritis (UA) by analyzing GM-CSF expression and source, macrophage polarization and density in joints of patients with UA evolving to RA or PsA compared with established RA or PsA, respectively.MethodsSynovial tissue (ST) from patients with UA evolving to RA (UA>RA, n=8), PsA (UA>PsA, n=9), persistent UA (UA, n=16), established RA (n=12) and PsA (n=10), and healthy controls (n=6), were analyzed. Cell source and quantitative expression of GM-CSF and proteins associated with pro-inflammatory (GM-CSF-driven) and anti-inflammatory (M-CSF-driven) macrophage polarization (activin A, TNFα, MMP12, and CD209, respectively) were assessed in ST CD163+ macrophages by multicolor immunofluorescence. GM-CSF and activin A levels were also quantified in paired synovial fluid samples. CD163+ macrophage density was determined in all groups by immunofluorescence.ResultsSynovial stromal cells (FAP+ CD90+ fibroblast, CD90+ endothelial cells) and CD163+ sublining macrophages were the sources of GM-CSF. ST CD163+ macrophages from all groups expressed pro-inflammatory polarization markers (activin A, TNFα, and MMP12). Expression of the M-CSF-dependent anti-inflammatory marker CD209 identified two macrophage subsets (CD163+ CD209high and CD163+ CD209low/-). CD209+ macrophages were more abundant in ST from healthy controls and PsA patients, although both macrophage subtypes showed similar levels of pro-inflammatory markers in all groups. In paired synovial fluid samples, activin A was detected in all patients, with higher levels in UA>RA and RA, while GM-CSF was infrequently detected. ST CD163+ macrophage density was comparable between UA>RA and UA>PsA patients, but significantly higher than in persistent UA.ConclusionsGM-CSF is highly expressed by sublining CD90+ FAP+ synovial fibroblasts, CD90+ activated endothelium and CD163+ macrophages in different types of arthritis. The polarization state of ST macrophages was similar in all UA and established arthritis groups, with a predominance of pro-inflammatory GM-CSF-associated markers. CD163+ macrophage density was significantly higher in the UA phases of RA and PsA compared with persistent UA. Taken together, our findings support the idea that GM-CSF is a strong driver of macrophage polarization and a potential therapeutic target not only in RA but also in PsA and all types of UA.

MEFV mutations have been documented in patients with palindromic rheumatism (PR) who do not meet FMF criteria, and RF and ACPA positive RA may start with PR.To analyze the clinical phenotype and disease evolution of patients with intermittent, palindromic-like (PL) arthritis seen in our Arthritis Unit according to the RF, ACPA and MEFV mutation status.MEFV genotyping was done in 76 patients with PL arthritis as defined by predominantly short attacks (≤7days) and a relapsing course. Characteristics of arthritic episodes, RF and ACPA positivity, and the colchicine response were retrospectively collected. Patients were stratified and evaluated according to MEFV mutations and/or positive autoantibodies (ACPA and/or RF).Among the patients, 26.3% (20/76) had a MEFV mutation and 23 (30%) were ACPA and/or RF positive. MEFV mutations and/or autoantibody status allowed four PL arthritis patients to be distinguished: group I (MEFV+), with younger age of onset, short duration attacks (3days), mainly located in the knee, more frequent non-articular manifestations (fever, pericarditis or abdominal pain) and good response to colchicine; group II (autoantibody+) is older than group I, with the same frequency of short attacks, but the most affected joints were the wrists and small joints of hands: 48% met RA classification criteria during follow-up and were taking DMARDs; group III (MEFV- and autoantibody-) was the most frequent (48%) and clinically heterogeneous group; 51% had attacks lasting3days, and 15 patients developed criteria of immune-mediated inflammatory, autoinflammatory or infectious diseases. Group IV (MEFV+ associated with preexisting immune-inflammatory disease), was associated with very short attacks, like groups I and II, superimposed or coincident with definite immune-inflammatory disease, including seropositive RA, with good response to colchicine.Patients with PL arthritis can be classified in four groups according to the presence or not of MEFV mutations and ACPA/RF antibodies with a different clinical evolution and therapeutic response.

Background: MEFV mutations were documented in patients with palindromic rheumatism (PR) who do not meet Familial Mediterranean Fever (FMF) criteria, and RF and ACPA positive rheumatoid arthritis (RA) may start with PR. We retrospectively analyzed the clinical phenotype and disease evolution of patients with palindromic-like (PR-L) arthritis according to ACPA/RF and MEFV mutation status. Methods: MEFV genotyping was undertaken in 76 patients with PR-L arthritis as determined by short attacks ( < 7 days) and relapsing course. Characteristics of arthritis episodes, RF and ACPA positivity, and colchicine response were retrospectivelly collected. Patients were stratified according the presence of MEFV mutations and/or ACPA/RF status. Findings: 26.3% (20/76) of patients had MEFV mutations and 23 (30%) were ACPA and/or RF positive. After stratification, we can distinguish four groups of PR-L arthritis patients. Group I (MEFV +ve) with younger age of onset, short duration attacks ( 3 days, and 15 patients developed criteria of immune-mediated inflammatory (IMID), autoinflammatory or infectious disease. Group IV (MEFV +ve associated to pre-existing IMID) had very short-attacks (

The visualization and localization of blood vessels in Laser Speckle Contrast Imaging is an important task in biomedical applications such as dermatology, neurosciences, and ophthalmology, as it allows to determine the presence of blood vessels and also to estimate properties such as blood flow. This work establishes a review of visualization methods for contrast calculation and improvement in Laser Speckle Contrast Imaging. In addition, it is presented the localization of blood vessels in an automatic way through clustering. The results suggest that the localization of blood vessels depends largely on the calculation and improvement of contrast. If the blood vessel and biological tissue regions are well separated from each other, and the noise level is low, K-means clustering is a powerful tool for locating blood vessels in Laser Speckle Contrast Imaging.

With the recent identification of the Wabash Valley Seismic Zone in addition to the New Madrid Seismic Zone, Indiana’s Department of Transportation (INDOT) has become concerned with ensuring the adequate seismic performance of their bridge network. While INDOT made an effort to reduce the seismic vulnerability of newly-constructed bridges, many less recent bridges still have the potential for vulnerability. Analyzing these bridges’ seismic vulnerability is a vital task. However, developing a detailed dynamic model for every bridge in the state using information from structural drawings is rather tedious and time-consuming. In this study, we develop a simplified dynamic assessment procedure using readily-available information from INDOT’s Bridge Asset Management Program (BIAS), to rapidly identify vulnerable bridges throughout the state. Eight additional data items are recommended to be added into BIAS to support the procedure. The procedure is applied in the Excel file to create a tool, which is able to automatically implement the simplified bridge seismic analysis procedure. The simplified dynamic assessment procedure and the Excel tool enable INDOT to perform seismic vulnerability assessment and identify bridges more frequently. INDOT can prioritize these bridges for seismic retrofits and efficiently ensure the adequate seismic performance of their assets.

We reviewed the COVID-19 vaccines that reached phase III of clinical development. For each of the 10 vaccines identified, we described the technology used for vaccine development, the available data from phase III clinical trials, data on vaccine safety, and the role of new SARS-CoV-2 variants on vaccine efficacy.

This report describes a methodology for demand estimate through the improvement of load distribution factors in reinforced concrete flat-slab and T-beam bridges. The proposed distribution factors are supported on three-dimensional (3D) Finite Element (FE) analysis tools. The Conventional Load Rating (CLR) method currently in use by INDOT relies on a two-dimensional (2D) analysis based on beam theory. This approach may overestimate bridge demand as the result of neglecting the presence of parapets and sidewalks present in these bridges. The 3D behavior of a bridge and its response could be better modeled through a 3D computational model by including the participation of all elements. This research aims to investigate the potential effect of railings, parapets, sidewalks, and end-diaphragms on demand evaluation for purposes of rating reinforced concrete flat-slab and T-beam bridges using 3D finite element analysis. The project goal is to improve the current lateral load distribution factor by addressing the limitations resulting from the 2D analysis and ignoring the contribution of non-structural components. Through a parametric study of the slab and T-beam bridges in Indiana, the impact of selected parameters on demand estimates was estimated, and modifications to the current load distribution factors in AASHTO were proposed.

Background and aim There is increasing interest regarding SARS-CoV-2 infection in patients with autoimmune and immune-mediated inflammatory diseases (AI/IMID) with some discrepancies in different cohorts about their risk and outcomes. The aim was to describe a multidisciplinary cohort of patients with AI/IMID and symptomatic SARS-CoV-2 infection in a single tertiary center and analyze sociodemographic, clinical, and therapeutic factors associated with poor outcomes. Methods A retrospective observational study was conducted from the 1st of March until May 29th, 2020 in a University tertiary hospital in Barcelona, Spain. Patients with an underlying AI/IMID and symptomatic SARS-CoV-2 infection were identified in our local SARS-CoV-2 infection database. Controls (2:1) were selected from the same database and matched by age and gender. The primary outcome was severe SARS-CoV-2 infection, which was a composite endpoint including admission to the intensive care unit (ICU), need for mechanical ventilation (MV), and/or death. Several covariates including age, sex, and comorbidities among others were combined into a multivariate model having severe SARS-CoV-2 as the dependent variable. Also, a sensitivity analysis was performed evaluating AID and IMID separately. Results The prevalence of symptomatic SARS-CoV-2 infection in a cohort of AI/IMID patients was 1.3%. Eighty-five patients with AI/IMID and symptomatic SARS-CoV-2 were identified, requiring hospitalization in 58 (68%) cases. A total of 175 patients admitted for SARS-CoV-2 (58 with AI/IMID and 117 matched-controls) were analyzed. In logistic regression analysis, a significant inverse association between AI/IMID group and severe SARS-CoV-2 (OR 0.28; 95% CI 0.12–0.61; p = 0.001), need of MV (OR 0.20; IC 95% 0.05–0.71; p = 0.014), and ICU admission (OR 0.25; IC 95% 0.10–0.62; p = 0.003) was found. Conclusions Patients with AI/IMID who require admission for SARS-CoV-2 infection have a lower risk of developing severe disease, including the need to stay in the ICU and MV., Highlights • Patients with AI/IMID fwho required admission for SARS CoV2 infection have a lower risk of developing severe disease. • Among patients with AID and IMID, there were no differences in terms of severity. • According to the 7-category ordinal scale, maximum oxygen requirement was lower among AI/IMID group.

BackgroundThe mechanisms by which only some rheumatoid arthritis (RA) patients respond favorably to TNF blockade are still poorly characterized. The goal of this study was to identify biological features that explain this differential response using a multilevel transcriptome analysis of the synovial membrane.MethodsSynovial samples from 11 patients on anti-TNF therapy were obtained by arthroscopy at baseline and week 20. Analysis of the synovial transcriptome was performed at the gene, pathway, and cell-type levels. Newly characterized pathogenic cell types in RA, peripheral helper T cells (TPH), and CD34-THY1+ fibroblasts were estimated using a cell-type deconvolution approach. TPHassociation was validated using immunofluorescence. External validation was performed on an independent dataset.ResultsAfter multiple-test correction, 16 and 4 genes were differentially expressed at baseline and week 20, respectively. At the pathway level, 86 and 17 biological processes were significantly enriched at baseline and week 20, respectively. Longitudinal expression changes were associated with a drastic decrease of innate immune activity (P P PHcells at baseline and a better response (P = 0.026). Lower TPHcells were maintained in good responders up to week 20 (P = 0.032). Immunofluorescent analyses confirmed the accuracy of the cell-type estimation (r2 = 0.58,P = 0.005) and an association with response. TPHassociation with anti-TNF response was validated in an independent sample of RA patients (P = 0.0040).ConclusionsA lower abundance in the synovial membrane of the pathogenic T cell type newly associated with RA, peripheral helper T lymphocyte, is associated with a good response to anti-TNF therapy. Major changes in the myeloid cell compartment were also observed in response to therapy. The results of this study could help develop more effective therapies aimed at treating the pathogenic mechanisms in RA that are currently not well targeted by anti-TNF agents.

Since 2015, NHERI, or the Natural Hazards Engineering Research Infrastructure, began research operations supported by the United States National Science Foundation (NSF) as a distributed, multi-user national facility that provides the natural hazards research community with access to a powerful research infrastructure. NHERI is comprised of separate research infrastructure awards for a Network Coordination Office (NCO), Cyberinfrastructure, a Computational Modeling and Simulation Center, eight Experimental Facilities, and CONVERGE (an initiative to advance social sciences and interdisciplinary research). Awards made for NHERI contribute to NSF's role in the National Earthquake Hazards Reduction Program and the National Windstorm Impact Reduction Program of the United States. The mission of NHERI is to provide the earthquake, wind, coastal engineering, and social sciences communities with access to research infrastructure, education, and community outreach activities focused on improving the resilience and sustainability of the civil infrastructure against earthquakes, windstorms, and associated natural events such as tsunami and coastal storm surge. In this paper, the role and key NHERI activities are described for the NCO, which is led by Purdue University, along with partner institutions—the University of Texas at San Antonio, North Carolina State University, Texas Tech University, the U.S. Naval Research Laboratory, and the University of Hawaii at Manoa. The NHERI NCO serves as a focal point and leader of a multi-hazards research community, and maintains a community-based NHERI science plan. It manages scheduling for partner NHERI Experimental Facilities and coordinates all components to ensure effective and fair governance, efficient testing, and user support within a safe environment. Another important role of the NCO is to lead NHERI-wide educational and outreach activities: the network facilitates educational experiences ranging from summer programs for undergraduates to workshops for post-docs and early-career faculty that also both involve development of K-12 lesson plans. The NCO works to develop strategic national and international partnerships and to coordinate NHERI activities with other awardee components to form a cohesive and fully-integrated global natural hazards engineering research infrastructure that fosters collaboration in new ways.

The most common approach to optically generate and manipulate bubbles in liquids involves temperature gradients induced by CW lasers. In this work, we present a method to accomplish both the generation of microbubbles and their 3D manipulation in ethanol through optothermal forces. These forces are triggered by light absorption from a nanosecond pulsed laser (λ = 532 nm) at silver nanoparticles photodeposited at the distal end of a multimode optical fiber. Light absorbed from each laser pulse quickly heats up the silver-ethanol interface beyond the ethanol critical-point (∼ 243 °C) before the heat diffuses through the liquid. Therefore, the liquid achieves a metastable state and owing to spontaneous nucleation converted to a vapor bubble attached to the optical fiber. The bubble grows with semi-spherical shape producing a counterjet in the final stage of the collapse. This jet reaches the hot nanoparticles vaporizing almost immediately and ejecting a microbubble. This microbubble-generation mechanism takes place with every laser pulse (10 kHz repetition rate) leading to the generation of a microbubbles stream. The microbubbles' velocities decrease as they move away from the optical fiber and eventually coalesce forming a larger bubble. The larger bubble is attracted to the optical fiber by the Marangoni force once it reaches a critical size while being continuously fed with each bubble of the microbubbles stream. The balance of the optothermal forces owing to the laser-pulse drives the 3D manipulation of the main bubble. A complete characterization of the trapping conditions is provided in this paper.

The visualization and localization of blood vessels in Laser Speckle Contrast Imaging is an important task to determine the presence of blood vessels in the biological tissue. However, Laser Speckle Contrast Imaging has some drawbacks when the depth of the blood vessels increases. This work establishes a methodology based on a wavelet approach to improve the localization of blood vessels in in-vitro contrast images. It also determines a useful exposure time to improve the localization of blood vessels. The results show that the wavelet approach allows blood vessels to be located up to 510µm deep under a skin phantom. In addition, it states that high exposure times increase the percentage of similarity in traditional models and visualization enhancement models.

Pneumonia is the leading cause of infectious related death costing 12 billion dollars annually in the United States alone. Despite improvements in clinical care, total mortality remains around 4%, with inpatient mortality reaching 5-10%. For unknown reasons, mortality risk remains high even after hospital discharge and there is a need to identify those patients most at risk. Also of importance, clinical symptoms alone do not distinguish viral from bacterial infection which may delay appropriate treatment and may contribute to short-term and long-term mortality. Biomarkers have the potential to provide point of care diagnosis, identify high-risk patients, and increase our understanding of the biology of disease. However, there have been mixed results on the diagnostic performance of many of the analytes tested to date. Urine represents a largely untapped source for biomarker discovery and is highly accessible. To test this hypothesis, we collected urine from hospitalized patients with community-acquired pneumonia (CAP) and performed a comprehensive screen for urinary tract microbiota signatures, metabolite, and cytokine profiles. CAP patients were diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) etiologies and compared with healthy volunteers. Microbiome signatures showed marked shifts in taxonomic levels in patients with bacterial etiology versus influenza and CAP versus normal. Predictive modeling of 291 microbial and metabolite values achieved a +90% accuracy with LASSO in predicting specific pneumonia etiology. This study demonstrates that urine from patients hospitalized with pneumonia may serve as a reliable and accessible sample to evaluate biomarkers that may diagnose etiology and predict clinical outcomes.Author SummaryUrine has been classically considered sterile since most microorganisms are not readily culturable under healthy circumstances. Further, many pneumonia patients are immediately placed on antibiotics rendering culture-based techniques useless. However, the advent of next generation sequencing has enabled unprecedented analysis of the microbial communities – living or detected as free DNA – found in many niches of the human body. Here, we describe a urine microbiome as well as metabolites and cytokines measured in patients newly admitted to the hospital diagnosed with influenza or bacterial (S. aureus and S. pneumoniae) infection pneumonia, compared with healthy controls. Using these parameters alone, we were able to achieve high success in predicting patient pneumonia. This study provides a proof of concept that urine samples, which are easily accessible in outpatient and inpatient settings, could provide additional diagnostic insights to patient infectious status and future risk factor for complication.

Migrants represent a diverse population comprising workers, students, undocumented individuals, and refugees. Worldwide, approximately 1 billion people were considered migrants in 2016. Notably, about 65 million of these migrants were forcibly displaced from their homes, and 20 million were considered refugees. While the geopolitical consequences of such migration continue to be considered, less is known about the impact of these events on the respiratory health of migrants and refugees. In recognition of this knowledge gap, the American Thoracic Society and the European Respiratory Society brought together investigators with diverse and relevant expertise to participate in a workshop and develop a consensus on research needs on the respiratory health of migrants and refugees. The workshop focused on environmental and occupational hazards, chronic noninfectious diseases, and respiratory infectious diseases, which were presented by experts in three distinct sessions, each culminating with panel discussions. A writing committee collected summaries prepared by speakers and other participants, and the information was collated into a single document. Recommendations were formulated, and differences were resolved by discussion and consensus. The group identified important areas of research need, while emphasizing that reducing the burden of pulmonary, critical care, and sleep disorders in migrants and refugees will require a concerted effort by all stakeholders. Using best research practices, considering how research impacts policies affecting migrant and refugee populations, and developing new approaches to engage and fund trainees, clinical investigators, and public health practitioners to conduct high-quality research on respiratory health of migrants and refugees is essential.

This study presents a physics-based rib-scale finite element (FE) model to study bond-zone behavior for spliced longitudinal bars in reinforced concrete beams subjected to monotonically increasing loading. In this model, a high-resolution mesh is used in the vicinity of the bar-concrete interface to capture the geometry of the ribs on the reinforcing steel. At the concrete-bar interface, a contact formulation that properly represents normal and frictional force transfer is used; adhesion between concrete and steel is ignored. The FE model is calibrated using data from beam splice tests performed by Ramirez and Russell [1] . It is observed that concrete tensile strength and tangential friction at the concrete-steel interface determine simulated response; these quantities are calibrated to provide accurate simulation of experimental results. The calibrated model provides results in good agreement with test data. Load-displacement response as well as concrete crack patterns are accurately simulated, and the proposed model can distinguish between the behavior of uncoated and epoxy-coated deformed bars as well as simulate the impact on bond strength of confinement provided by transverse steel.

Objectives To develop recommendations for the management of methotrexate (MTX) in psoriatic arthritis (PsA), based on best evidence and experience. Methods A group of 12 experts on MTX use was selected. The coordinators formulated 14 questions about the use of MTX in PsA patients (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed 12 preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence Based Medicine and the level of agreement with the Delphi technique (two rounds). Agreement was established if at least 80% of the experts voted yes (yes/no). Results A total of 12 preliminary recommendations on the use of MTX were proposed, 9 of which were accepted. One was included in a different recommendation and other two were not voted on and were thereafter clarified in the main text. Conclusions These recommendations aim to answer frequent questions and help in decision making strategies when treating PsA patients with MTX.

The anti-interleukin-1 receptor antagonist, anakinra, was approved for the treatment of rheumatoid arthritis (RA) more than 12 years ago. However, its adverse effects are not well known. Areas covered: We review the safety profile of anakinra, analyzing clinical trials, observational studies, and registry data. Expert opinion: Due to its lower efficacy compared with other biological therapies approved for RA and its daily subcutaneous administration, anakinra is used only marginally for the treatment of RA. This has limited the experience with this drug in RA, with a lack of data from long-term observational studies or registries. From the five clinical trials performed, and given the unfeasibility of developing new studies of anakinra in RA, it may be concluded that site injection reactions, infections at higher doses (100 mg), and immunogenicity are the most frequent adverse events related to anakinra administration.

This paper presents a new decoder algorithm for the double space–time transmit diversity (DSTTD) system. The decoder is based on the QRD-M algorithm, which performs a breadth-first search of possible solutions tree. The search is simplified by skipping unlikely candidates, and it is stopped when no promising candidates are left. Furthermore, the search is divided into three concurrent iterations, making possible a fast, parallel implementation either in hardware or software. After presenting an analysis of the capacity and diversity of DSTTD, we present performance results showing that the proposed decoder is capable of achieving near maximum likelihood performance. We also show that the proposed algorithm exhibits lower computational complexity than other existing maximum likelihood detectors.

Our study demonstrated real-world, direct effectiveness of 13-valent pneumococcal conjugate vaccine against vaccine-type community-acquired pneumonia following introduction into a routine immunization program among adults aged ≥65 years, many of whom had immunocompromising and chronic medical conditions., Background Following universal recommendation for use of 13-valent pneumococcal conjugate vaccine (PCV13) in US adults aged ≥65 years in September 2014, we conducted the first real-world evaluation of PCV13 vaccine effectiveness (VE) against hospitalized vaccine-type community-acquired pneumonia (CAP) in this population. Methods Using a test-negative design, we identified cases and controls from a population-based surveillance study of adults in Louisville, Kentucky, who were hospitalized with CAP. We analyzed a subset of CAP patients enrolled 1 April 2015 through 30 April 2016 who were aged ≥65 years and consented to have their pneumococcal vaccination history confirmed by health insurance records. Cases were defined as hospitalized CAP patients with PCV13 serotypes identified via culture or serotype-specific urinary antigen detection assay. Remaining CAP patients served as test-negative controls. Results Of 2034 CAP hospitalizations, we identified PCV13 serotypes in 68 (3.3%) participants (ie, cases), of whom 6 of 68 (8.8%) had a positive blood culture. Cases were less likely to be immunocompromised (29.4% vs 46.4%, P = .02) and overweight or obese (41.2% vs 58.6%, P = .01) compared to controls, but were otherwise similar. Cases were less likely to have received PCV13 than controls (3/68 [4.4%] vs 285/1966 [14.5%]; unadjusted VE, 72.8% [95% confidence interval, 12.8%−91.5%]). No confounding was observed during adjustment for patient characteristics, including immunocompromised status, body mass index, and history of influenza and pneumococcal polysaccharide vaccination (adjusted VE range, 71.1%−73.3%). Conclusions Our study is the first to demonstrate real-world effectiveness of PCV13 against vaccine-type CAP in adults aged ≥65 years following introduction into a national immunization program.

Background Although not all health care-associated infections (HAIs) are preventable, reducing HAIs through targeted intervention is key to a successful infection prevention program. To identify areas in need of targeted intervention, robust statistical methods must be used when analyzing surveillance data. The objective of this study was to compare and contrast statistical process control (SPC) charts with Twitter's anomaly and breakout detection algorithms. Methods SPC and anomaly/breakout detection (ABD) charts were created for vancomycin-resistant Enterococcus, Acinetobacter baumannii, catheter-associated urinary tract infection, and central line-associated bloodstream infection data. Results Both SPC and ABD charts detected similar data points as anomalous/out of control on most charts. The vancomycin-resistant Enterococcus ABD chart detected an extra anomalous point that appeared to be higher than the same time period in prior years. Using a small subset of the central line-associated bloodstream infection data, the ABD chart was able to detect anomalies where the SPC chart was not. Discussion SPC charts and ABD charts both performed well, although ABD charts appeared to work better in the context of seasonal variation and autocorrelation. Conclusions Because they account for common statistical issues in HAI data, ABD charts may be useful for practitioners for analysis of HAI surveillance data.

Background and Objective: Blood vessel visualization is an essential task to treat and evaluate diseases such as port-wine stain. Laser Speckle Contrast Imaging (LSCI) have applications in the analysis of the microvasculature. However, it is often limited to superficial depths because the tissue among skin and microvasculature introduces noise in the image. To analyze microvasculature, traditional LSCI methods compute a Contrast Image (CI) by using a shifting window of fixed size and shape, which is inadequate in images with structures different types of morphologies in it, as happens in LSCI. This work aims to reduce the noise in the CIs to improve the visualization of blood vessels at high depths ( > 300 μ m). Methods: The proposed method processes the CIs with analysis windows that change their size and shape for each pixel to compute the contrast representation with pixels more representatives to the region. Results: We performed experiments varying the depth of the blood vessels, the number of frames required to compute the representation, and the blood flow in the blood vessel. We looked for an improvement in the Contrast to Noise Ratio (CNR) in the periphery of the blood vessels using an analysis of variance. Finding that the adaptive processing of the contrast images allows a significant noise attenuation, translated into a better visualization of blood vessels. An average CNR of 2.62 ± 1 and 5.26 ± 1.7 was reached for in-vitro and in-vivo tests respectively, which is higher in comparison with traditional LSCI approaches. Conclusions: The results, backed by the measured CNR, obtained a noise reduction in the CIs, this means a better temporal and spatial resolution. The proposed awK method can obtain an image with better quality than the state-of-the-art methods using fewer frames.

Post-event building reconnaissance teams have a clear mission. These teams of trained professional engineers, academic researchers and graduate students are charged with collecting perishable data to be used for learning from disasters. A tremendous amount of perishable visual data can be generated in just a few days. However, only a small portion of the data collected is annotated and used for scientific purposes due to the tedious and time-consuming processes needed to sift through and analyze them. This crucial process still significantly relies on trained human operators. To distill such information in an efficient manner, we introduce a novel and powerful method for post-disaster evaluation by processing and analyzing big visual data in an autonomous manner. Recent convolutional neural network (CNN) algorithms are implemented to extract visual content of interest automatically from the collected images. Image classification and object detection are incorporated into the procedures to achieve accurate extraction of target contents of interest. As an illustration of the computational technique and its capabilities, collapse classification and spalling detection in concrete structures are demonstrated using a large volume of images gathered from past earthquake disasters.

The coherent-mode representation is a fundamental tool that helps us understand the processes of producing and propagating optical fields. In this work, such representation for self-imaging phenomena under partially coherent illumination is presented within the frame of partial coherence theory in the space-frequency domain. Additionally, it is shown that the well-known Talbot and Lau effects are particular cases included in this new formalism. When complete coherence of the field is considered, the general expression for coherent self-imaging of optical fields is obtained (Talbot effect for both linear and circular gratings are presented); on the other hand, when an incoherent superposition of an infinite number of modes are considered, the expression to describe the Lau effect is obtained.

The visualization and localization of blood vessels is an important task to determine the presence and the health status of microvasculature in the biological tissue. Laser Speckle Contrast Imaging is one of the most widely employed techniques to study blood vessels; even so, it has some drawbacks in analyzing deep blood vessels ( > 100 μ m ) since the image noise level increases. The Wavelet Approach is a model of automatic denoising for contrasted in vitro Raw Speckle images using an energy criterion. The criterion selects the more suitable denoising level from the Discrete Wavelet Transform decomposition using the detail coefficients. Then, the segmentation of low-noise images by mathematical morphology techniques establish the blood vessel and biological tissue location. Finally, the region corresponding to the blood vessel and the low-noise images are used to improve the visualization of blood vessels. Results show that a Wavelet Approach improves the visualization of blood vessels up to a depth of 400 μ m . Furthermore, the proposed model demonstrates that the automatic denoising criterion improves the localization of superficial ( ≤ 100 μ m ) and deep ( > 100 μ m ) blood vessels.

Objective To determine clinical and sonographic biomarkers predicting structural damage progression at 12 months of follow-up as measured by magnetic resonance imaging (MRI) in rheumatoid arthritis (RA) patients in clinical remission. Patients and methods We included patients with RA in clinical remission, defined as 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR) 6 months. Ultrasound scans of both hands and knees and MRI of the dominant hand were performed at baseline and at 12 months. Results Out of 55 patients, 42 completed the follow-up. Among them, 78% were female, aged (median) 54 years; disease duration was 93 months. In total, 12 (28%) patients were taking oral prednisone, 34 (81%) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 20 (47%) biological therapies. At baseline, 45% fulfilled criteria previously defined for ultrasound-defined active synovitis (UdAS) [PD (power Doppler) signal + synovial hyperplasia ≥2]. Multivariate analysis showed significant associations between baseline MRI erosion score, body mass index (BMI), disease duration, prednisone treatment, absence of biologic and csDMARDs, UdAS, and MRI erosion score progression after 12 months. In an exploratory analysis, serum levels of calprotectin correlated significantly with bone edema progression. Conclusions We identified clinical and sonographic markers of structural damage progression after 12 months follow-up in patients with RA in clinical remission. Meeting the criteria of ultrasound active synovitis, defined as simultaneous relevant synovial hyperplasia and PD, was associated with erosion progression after 12 months. Calprotectin was associated with bone edema, in an exploratory analysis.

International experts suggest tailoring antibiotic duration in community-acquired pneumonia (CAP) according to patients' characteristics. We aimed to assess the effectiveness of an individualized approach to antibiotic duration based on time in which CAP patients reach clinical stability during hospitalization. In a multicenter, non-inferiority, randomized, controlled trial hospitalized adult patients with CAP reaching clinical stability within 5 days after hospitalization were randomized to a standard vs. individualized antibiotic duration. In the Individualized group, antibiotics were discontinued 48 h after the patient reached clinical stability, with at least five days of total antibiotic treatment. Early failure within 30 days was the primary composite outcome. 135 patients were randomized to the Standard group and 125 to the Individualized group. The trial was interrupted by the safety committee because of an apparent inferiority of the Individualized group over the Standard treatment: 14 (11.2%) patients in the Individualized group experienced early failure vs. 10 (7.4%) patients in the Standard group, p = 0.200, at the intention-to-treat analysis. 30-day mortality rate was four-time higher in the Individualized group than the Standard group. Shortening antibiotic duration according to patients' characteristics still remains an open question.

Background Understanding the burden of community-acquired pneumonia (CAP) is critical to allocate resources for prevention, management, and research. The objectives of this study were to define incidence, epidemiology, and mortality of adult patients hospitalized with CAP in the city of Louisville, and to estimate burden of CAP in the US adult population. Methods This was a prospective population-based cohort study of adult residents in Louisville, Kentucky, from 1 June 2014 to 31 May 2016. Consecutive hospitalized patients with CAP were enrolled at all adult hospitals in Louisville. The annual population-based CAP incidence was calculated. Geospatial epidemiology was used to define ecological associations among CAP and income level, race, and age. Mortality was evaluated during hospitalization and at 30 days, 6 months, and 1 year after hospitalization. Results During the 2-year study, from a Louisville population of 587499 adults, 186384 hospitalizations occurred. A total of 7449 unique patients hospitalized with CAP were documented. The annual age-adjusted incidence was 649 patients hospitalized with CAP per 100000 adults (95% confidence interval, 628.2-669.8), corresponding to 1591825 annual adult CAP hospitalizations in the United States. Clusters of CAP cases were found in areas with low-income and black/African American populations. Mortality during hospitalization was 6.5%, corresponding to 102821 annual deaths in the United States. Mortality at 30 days, 6 months, and 1 year was 13.0%, 23.4%, and 30.6%, respectively. Conclusions The estimated US burden of CAP is substantial, with >1.5 million unique adults being hospitalized annually, 100000 deaths occurring during hospitalization, and approximately 1 of 3 patients hospitalized with CAP dying within 1 year.

To assess the effectiveness and survival of ustekinumab (UST) among patients with psoriatic arthritis (PsA) treated under routine clinical care.Multicenter study. Epidemiological and clinical data was collected through electronic medical records of all patients with PsA who started UST in 15 hospitals of Spain.Two hundred and one patients were included, 130 (64.7%) with 45 mg and 71 (35.3%) with 90 mg. One hundred and thirty one patients (65.2%) had previously received another biological therapy. The median baseline DAS 28 ESR was 3.99, and Psoriasis Area and Severity Index (PASI) was 3. Overall, there was a significant decrease in DAS66/68 CRP, swollen joint count (SJC), tender joint count (TJC), and PASI in the first month of treatment, with earlier improvement in skin (PASI) than joints outcomes. Survival was numerically lower in patients with UST 45 mg (58.1%) than 90 mg (76.1%), although significant differences were not found (p = 0.147). When comparing naïve and 1 TNF blocker versus 2 TNF blocker-experienced patients, a significantly earlier response was seen in the former group regarding SJC (p = 0.029) at 1 month. Fifty-one patients (25.3%) stopped UST due to joint inefficacy and 4 patients due to adverse events (1.9%). Drug survival was significantly better in patients with fewer lines of previous biological agents (p = 0.003 for 1 TNF blocker versus 2 TNF blocker users).UST was effective in PsA patients in a routine clinical care setting. Patients with UST 90 mg and fewer lines of previous biologics achieved better and faster responses. Key Points • Largest cohort of patients with PsA in treatment with UST with specific rheumatological indication. • First cohort of patients with PsA comparing effectiveness of UST according to 45/90 mg dose.

Hand hygiene is one of the most important interventions in the quest to eliminate healthcare-associated infections, and rates in healthcare facilities are markedly low. Since hand hygiene observation and feedback are critical to improve adherence, we created an easy-to-use, platform-independent hand hygiene data collection process and an automated, on-demand reporting engine.A 3-step approach was used for this project: 1) creation of a data collection form using Google Forms, 2) transfer of data from the form to a spreadsheet using Google Spreadsheets, and 3) creation of an automated, cloud-based analytics platform for report generation using R and RStudio Shiny software.A video tutorial of all steps in the creation and use of this free tool can be found on our YouTube channel: https://www.youtube.com/watch?v=uFatMR1rXqUt. The on-demand reporting tool can be accessed at: https://crsp.louisville.edu/shiny/handhygiene.This data collection and automated analytics engine provides an easy-to-use environment for evaluating hand hygiene data; it also provides rapid feedback to healthcare workers. By reducing some of the data management workload required of the infection preventionist, more focused interventions may be instituted to increase global hand hygiene rates and reduce infection.

This report contains the findings of a synthesis study on the use of link slabs to eliminate intermediate joints in bridges of Indiana. The study was conducted under the sponsorship of the Joint Transportation Research Program. The motivation for the study was to investigate this promising technique to mitigate the damage associated with expansion joints that has long been recognized as a persistent and costly issue negatively impacting the bridge service life. The report summarizes the background information and motivation for the study. It also provides a description of the report organization. The results of an extensive literature review of DOTs’ experience related to the use of this system and main research findings are presented as well as construction practice and examples of application. The results of the analysis of a bridge in Indiana where the link slab system has been implemented are presented. The bridge connecting the State Road 68 over the Interstate 64 was selected as a representative bridge based on the analysis of the inspection. A parametric study on the effects of various parameters was conducted to evaluate the effect of support conditions and debonded length on the stress distribution and potential crack initiation in link slabs. Each variable was investigated separately to isolate its effect. Two bridge structures were investigated in this study. The first structure (Case 1) represents a bridge structure rehabilitated using link slabs. A second bridge structure (Case 2) with the same geometrical and material properties, but with a continuous and fully bonded deck, was also included in the parametric study for comparison purposes. This structure simulated new bridge construction.

Purpose: To report a case of cystoid macular edema (CME) secondary to juvenile idiopathic arthritis (JIA)-associated uveitis.Case report: 26-year-old female patient presented with CME in both eyes. CME became refractory and TCZ-IV was initiated. After 12 infusions was stopped because grade 1 neuropenia developed. On examination,visual acuity of the right eye was 20/80. Spectral domain optical coherence tomography (SD-OCT) of the right eye revealed CME. Subcutaneous (TCZ-SC) was initiated. After six injections of TCZ-SC, ophthalmic examination revealed no signs of active inflammation, and central foveal thickness decreased.Conclusion: TCZ-SC seems to have a role in the treatment of CME secondary to juvenile idiopathic arthritis (JIA)-associated uveitis.

We present the generation and 3D manipulation of microbubbles by thermal gradients, induced by low power nanosecond pulsed laser in non-absorbent liquids. Light absorption at photodeposited silver nanoparticles on the optical fiber tip heat up the surrounding liquid, which leads to optothermal effects. With each laser pulse a microbubble is detached from the optical fiber end, creating a microbubbles-stream. The microbubbles move away from the optical fiber end driven by non-spherical cavitation until they coalesce creating a main-bubble which is attracted towards the optical fiber end by Marangoni force. In addition, the main-bubbles are under the influence of buoyancy and gravity forces, which act upwards and downwards, respectively. The balance of these forces allows the 3D manipulation of the main-bubble. The main-bubble position can be controlled by careful control of the pulse energy. To our knowledge this is the first time that 3D manipulation of microbubbles using pulsed lasers is demonstrated.