There is a great need in experimental biology for tools to study interactions between biological molecules and to profile expression levels of large numbers of proteins. This paper describes the ...fabrication, packaging and testing of a resonant mass sensor for the detection of biomolecules in a microfluidic format. The transducer employs a suspended microchannel as the resonating element, thereby avoiding the problems of damping and viscous drag that normally degrade the sensitivity of resonant sensors in liquid. Our device differs from a vibrating tube densitometer in that the channel is very thin, which enables the detection of molecules that bind to the channel walls; this provides a path to specificity via molecular recognition by immobilized receptors. The fabrication is based on a sacrificial polysilicon process with low-stress low-pressure chemical-vapor deposited (LPCVD) silicon nitride as the structural material, and the resonator is vacuum packaged on the wafer scale using glass frit bonding. Packaged resonators exhibit a sensitivity of 0.8 ppm/(ngmiddotcm 2 ) and a mechanical quality factor of up to 700. To the best of our knowledge, this quality factor is among the highest so far reported for resonant sensors with comparable surface mass sensitivity in liquid
While significant progress continues to be made in the early detection and therapeutic management of primary tumors, the incidence of metastatic disease remains the major cause of mortality. ...Accordingly, the development of novel effective therapies that can ameliorate dissemination and secondary tumor growth are a clinical priority. The identification of genetic and functional alterations in cancer cells that affect factors implicated in the metastatic process is critical for designing preventive and therapeutic strategies. Evidence implicating the protein deleted in liver cancer-1 (DLC1), a Rho GTPase activator, in metastasis has accumulated to a point where DLC1 may be considered as a metastasis suppressor gene. This review presents evidence supporting an anti-metastatic role for DLC1 in several human cancers and discusses the mechanisms contributing to its inhibitory effects. In addition, promising opportunities for therapeutic interventions based on DLC1 function and downstream pathways involved in the metastatic process are considered.
We propose a nonwearable hydraulic bed sensor system that is placed underneath the mattress to estimate the relative systolic blood pressure of a subject, which only differs from the actual blood ...pressure by a scaling and an offset factor. Two types of features are proposed to obtain the relative blood pressure, one based on the strength and the other on the morphology of the bed sensor ballistocardiogram pulses. The relative blood pressure is related to the actual by a scale and an offset factor that can be obtained through calibration. The proposed system is able to extract the relative blood pressure more accurately with a less sophisticated sensor system compared to those from the literature. We tested the system using a dataset collected from 48 subjects right after active exercises. Comparison with the ground truth obtained from the blood pressure cuff validates the promising performance of the proposed system, where the mean correlation between the estimate and the ground truth is near to 90% for the strength feature and 83% for the morphology feature.
Tree mortality from major disturbances can greatly increase dead wood in forested areas, affecting fire intensity and behavior, wildlife habitat, and carbon dynamics. Accurately quantifying regional ...standing dead tree (SDT) pools, as conducted by the U.S. Forest Service Forest Inventory and Analysis (FIA) program, remains a prominent challenge. Little empirical work has been done accounting for structural changes in SDT volume across decay classes due to measurement and sampling challenges associated with SDT. Light-detection-and-ranging (LiDAR) represents a remote sensing technology with the potential to improve sampling efficacy and provide volume estimates of SDT via non-destructive sampling. Following this, the goal of this study was to explore the feasibility of empirically quantifying and assessing structural volume in southern pine SDT by decay class using terrestrial LiDAR. To meet this goal, we addressed three objectives, 1) construct empirical volume estimates of SDT by decay class using terrestrial LiDAR and a voxel-based, volume calculation algorithm capable of accounting for occlusion and point cloud quality, 2) develop allometric relationships of aboveground SDT component volumes by decay class and assess error in models and predictions, and 3) quantify proportion-remaining volume of SDT components from terrestrial LiDAR-derived volumes relative to predicted intact tree volumes. This study represents the first to develop empirically-based, terrestrial LiDAR-derived allometric volume relationships and proportion-remaining volume of SDT by decay class. Results indicate that terrestrial LiDAR-derived volumes of SDT produced robust allometric equations by decay class for total above-stump and stem-plus-bark components (adjusted R2 = 0.94–0.98). Allometric relationships for tops-and-branches comprised more variability, likely impacted by scan quality, having adjusted R2 values of ~0.52–0.59. Notably, the inclusion of height in allometric relationships for total above-stump volume precluded the need for decay class as a covariate, accounting for the variability inherent in each decay class. Importantly, this means that total above-stump allometric equations could be effective under different decay class systems or, more broadly, where no decay classes were measured, thus providing broad utility. Empirically-derived proportion-remaining volume of SDT components followed expected decreasing trends by decay class. Interestingly, proportion-remaining volume for tops-and-branches closely matched theoretically-derived values from a previous FIA-related study. Ultimately, terrestrial LiDAR was critical for efficiently measuring volume of southern pine SDT by decay class and for developing SDT-specific allometric relationships of volume and estimates of structural change by decay class. This study showcases the feasibility of LiDAR-derived, SDT-specific tools for improved accounting of SDT resources in FIA and other inventories.
•Estimated volume of 49 standing dead trees by decay class via terrestrial LiDAR.•Developed robust standing dead tree-specific volume allometry by decay class.•Height accounted for variability from decay classes for some allometric models.•Calculated empirical values of proportion-remaining volume of standing dead trees.•Lower scan quality impacted variability of tops-and-branches volume and allometry.
Abstract
Aims
The 2019 report from the European Society of Cardiology (ESC) Atlas provides a contemporary analysis of cardiovascular disease (CVD) statistics across 56 member countries, with ...particular emphasis on international inequalities in disease burden and healthcare delivery together with estimates of progress towards meeting 2025 World Health Organization (WHO) non-communicable disease targets.
Methods and results
In this report, contemporary CVD statistics are presented for member countries of the ESC. The statistics are drawn from the ESC Atlas which is a repository of CVD data from a variety of sources including the WHO, the Institute for Health Metrics and Evaluation, and the World Bank. The Atlas also includes novel ESC sponsored data on human and capital infrastructure and cardiovascular healthcare delivery obtained by annual survey of the national societies of ESC member countries. Across ESC member countries, the prevalence of obesity (body mass index ≥30 kg/m2) and diabetes has increased two- to three-fold during the last 30 years making the WHO 2025 target to halt rises in these risk factors unlikely to be achieved. More encouraging have been variable declines in hypertension, smoking, and alcohol consumption but on current trends only the reduction in smoking from 28% to 21% during the last 20 years appears sufficient for the WHO target to be achieved. The median age-standardized prevalence of major risk factors was higher in middle-income compared with high-income ESC member countries for hypertension {23.8% interquartile range (IQR) 22.5–23.1% vs. 15.7% (IQR 14.5–21.1%)}, diabetes 7.7% (IQR 7.1–10.1%) vs. 5.6% (IQR 4.8–7.0%), and among males smoking 43.8% (IQR 37.4–48.0%) vs. 26.0% (IQR 20.9–31.7%) although among females smoking was less common in middle-income countries 8.7% (IQR 3.0–10.8) vs. 16.7% (IQR 13.9–19.7%). There were associated inequalities in disease burden with disability-adjusted life years per 100 000 people due to CVD over three times as high in middle-income 7160 (IQR 5655–8115) compared with high-income 2235 (IQR 1896–3602) countries. Cardiovascular disease mortality was also higher in middle-income countries where it accounted for a greater proportion of potential years of life lost compared with high-income countries in both females (43% vs. 28%) and males (39% vs. 28%). Despite the inequalities in disease burden across ESC member countries, survey data from the National Cardiac Societies of the ESC showed that middle-income member countries remain severely under-resourced compared with high-income countries in terms of cardiological person-power and technological infrastructure. Under-resourcing in middle-income countries is associated with a severe procedural deficit compared with high-income countries in terms of coronary intervention, device implantation and cardiac surgical procedures.
Conclusion
A seemingly inexorable rise in the prevalence of obesity and diabetes currently provides the greatest challenge to achieving further reductions in CVD burden across ESC member countries. Additional challenges are provided by inequalities in disease burden that now require intensification of policy initiatives in order to reduce population risk and prioritize cardiovascular healthcare delivery, particularly in the middle-income countries of the ESC where need is greatest.
CD11c
T-bet
B cells generated during ehrlichial infection require CD4
T cell help and IL-21 signaling for their development, but the exact T cell subset required had not been known. In this study, we ...show in a mouse model of
that type 1 T follicular helper (T
) cells provide help to CD11c
T-bet
B cells via the dual secretion of IL-21 and IFN-γ in a CD40/CD40L-dependent manner. T
cell help was delivered in two phases: IFN-γ signals were provided early in infection, whereas CD40/CD40L help was provided late in infection. In contrast to T-bet
T cells, T-bet
B cells did not develop in the absence of B cell-intrinsic Bcl-6 but were generated in the absence of T-bet. T-bet-deficient memory B cells were largely indistinguishable from their wild-type counterparts, although they no longer underwent switching to IgG2c. These data suggest that a primary function of T-bet in B cells during ehrlichial infection is to promote appropriate class switching, not lineage specification. Thus, CD11c
memory B cells develop normally without T-bet but require Bcl-6 and specialized help from dual cytokine-producing T
cells.
Abstract
Introduction
Due to the aging of the population we are confronting ourselves with an increased number of patients with chronic heart failure which stands a prevalence of over 37,7 million ...cases worldwide, being a major public health issue, first by the substantial morbidity and mortality that carries and second by the economic burden it brings annually upon the health-care system.
The main purpose of this study is to test a machine learning algorithm which can predict, through voice analysis the acutisation of heart failure, considering the particularities of the patient's voice.
Methods
The data we have used has been collected from a total of 16 patients, 9 men and 7 women, ages between 65 and 91 years old, who have agreed to take part in the study.
The selective criteria of inclusion has been the cause of hospitalization, selecting only the patients presented with cardiogenic acute pulmonary edema, regardless the precipitation cause or other known cardiovascular comorbidities. With the same electronic device we have recorded each patient's voice, twice a day, starting from the day one of hospitalization, when their general status was critical, until the day of discharge, when they were clinically stable.
Each voice recording containing specific keywords has been associated to the most used classification system for heart failure, the New York Heart Association Functional Classification and introduced into the machine learning algorithm.
Results
After integrating the information from 15 patients, the algorithm has classified correctly the 16th patient into the third NYHA stage, based only on his voice recording.
Conclusion
Voice is a cheap and easy way to monitor a patient's health status. The algorithm we have used for analyzing the voice provides high accuracy results, but for a larger dataset it might not be the best choice as it is computationally expensive. We are looking to obtain larger datasets and to compute more complex voice analyzer algorithms.
Funding Acknowledgement
Type of funding sources: None.
We report on the fabrication of magnetite/salicylic acid/silica shell/antibiotics (Fe(3)O(4)/SA/SiO(2)/ATB) thin films by matrix-assisted pulsed laser evaporation (MAPLE) to inert substrates. ...Fe(3)O(4)-based powder have been synthesized and investigated by XRD and TEM. All thin films were studied by FTIR, SEM and in vitro biological assays using Staphylococcus aureus and Pseudomonas aeruginosa reference strains, as well as eukaryotic HEp-2 cells. The influence of the obtained nanosystems on the microbial biofilm development as well as their biocompatibility has been assessed. For optimum deposition conditions, we obtained uniform adherent films with the composition identical with the raw materials. Fe(3)O(4)/SA/SiO(2)/ATB thin films had an inhibitory activity on the ability of microbial strains to initiate and develop mature biofilms, in a strain- and antibiotic-dependent manner. These magnetite silica thin films are promising candidates for the development of novel materials designed for the inhibition of medical biofilms formed by different pathogenic agents on common substrates, frequently implicated in the etiology of chronic and hard to treat infections.
Cellular and molecular mechanisms of acute and chronic lung allograft rejection have yet to be clearly defined, and obliterative bronchiolitis (OB) remains the primary limitation to survival in lung ...transplant recipients (LTRs). We have previously shown that T-bet–deficient recipients of full major histocompatibility complex (MHC)-mismatched, orthotopic left lung transplants develop accelerated obliterative airway disease (OAD) in the setting of acute cellular rejection characterized by robust alloimmune CD8+ interleukin (IL)-17 and interferon (IFN)-γ responses that are attenuated with neutralization of IL-17. Azithromycin has been shown to be beneficial in some LTRs with bronchiolitis obliterans syndrome/OB. Here, we evaluated the effects of azithromycin on rejection pathology and T-cell effector responses in T-bet-/- recipients of lung transplants.
Orthotopic left lung transplantation was performed in BALB/c → B6 wild type or BALB/c → B6 T-bet-/- strain combinations as previously described. Mice treated with azithromycin received 10 mg/kg or 50 mg/kg subcutaneously daily. Lung allograft histopathology was analyzed at day 10 or day 21 post-transplantation, and neutrophil staining for quantification was performed using anti-myeloperoxidase. Allograft mononuclear cells were isolated at day 10 for T-cell effector cytokine response assessment using flow cytometry.
We show that while azithromycin significantly decreases lung allograft neutrophilia and CXCL1 levels and attenuates allospecific CD8+ IL-17 responses early post-transplantation, OAD persists in T-bet–deficient mice.
Our results indicate that lung allograft neutrophilia is not essential for the development of OAD in this model and suggest allospecific T-cell responses that remain despite marked attenuation of CD8+ IL-17 are sufficient for obliterative airway inflammation and fibrosis.
•The effects of azithromycin in a T-bet–deficient mouse lung transplantation model are studied.•Azithromycin significantly decreases both lung allograft neutrophilia and IL-17 responses.•Severe acute rejection pathology with obliterative airway inflammation and fibrosis persists despite azithromycin.
Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in ...patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction.
In this international, multicentre BAV registry, 1345 patients 51.0 (37.0-63.0) years, 71% male with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00-1.17, P = 0.046 and AR (HR 1.19 per 25 g/m2, 95% CI 1.11-1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06-2.23, P = 0.024; HR 1.68, 95% CI 1.17-2.42, P = 0.005; HR 1.59, 95% CI 1.03-2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35-4.60, P = 0.004 and HR 3.05, 95% CI 1.71-5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD.
LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD.
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