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Objective Prehospital rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in low-risk patient with a point-of-care troponin measurement reduces healthcare costs with similar safety to standard transfer to the hospital. Risk stratification is performed identical for men and women, despite important differences in clinical presentation, risk factors and age between men and women with NSTE-ACS. Our aim was to compare safety and healthcare costs between men and women in prehospital identified low-risk patients with suspected NSTE-ACS.Methods In the Acute Rule-out of non-ST-segment elevation acute coronary syndrome in the (pre)hospital setting by HEART (History, ECG, Age, Risk factors and Troponin) score assessment and a single poInt of CAre troponin randomised trial, the HEAR (History, ECG, Age and Risk factors) score was assessed by ambulance paramedics in suspected NSTE-ACS patients. Low-risk patients (HEAR score ≤3) were included. In this substudy, men and women were compared. Primary endpoint was 30-day major adverse cardiac events (MACE), secondary endpoints were 30-day healthcare costs and the scores for the HEAR score components.Results A total of 863 patients were included, of which 495 (57.4%) were women. Follow-up was completed in all patients. In the total population, MACE occurred in 6.8% of the men and 1.6% of the women (risk ratio (RR) 4.2 (95% CI 1.9 to 9.2, p

Background: The European Society of Cardiology (ESC) 0 h/1h algorithm is the preferred diagnostic strategy for chest pain patients in the emergency department (ED). It is suggested that adding clinical information to the algorithm improves its diagnostic performance. This study evaluates implementation of the ESC 0 h/1h algorithm in the ED and investigates the potential advantages of combining it with a clinical decision rule, which might be especially relevant in the heterogenous observation category. Methods: In this prospective cohort study, chest pain patients in whom the ESC 0 h/1h algorithm was applied were enrolled. HEART score components were collected. Diagnostic characteristics were determined for the algorithm with and without addition of the HEART score. Primary endpoint was a composite endpoint at 30-day follow-up, consisting of myocardial infarction and death. Results: A total of 668 patients were enrolled. The rule-in and rule-out categories consisted of 8.2% and 54.9% of the patients, respectively. Positive predictive value and specificity of the rule-in category were 67.3% and 97.1%, respectively. Negative predictive value (NPV) and sensitivity of the rule-out category were both 100%. In the observation category, a HEART score ≤ 3 yielded a NPV and sensitivity of 97.1% and 93.8%, respectively. Conclusion: The ESC 0 h/1h algorithm yielded a NPV and sensitivity of 100% for myocardial infarction and death at 30-day follow-up. Addition of the HEART score did not provide clinically relevant advantages. Although the HEART score can be used to guide diagnostic testing in the observation category, a low HEART score did not yield an NPV of > 99%.

Cacao pod's ideal harvesting time is when it is about to be ripe. Immature harvest would result in hard cacao beans not suitable for fermentation, while overripe cacao pods lead to fungal-infected, defective, and poor-quality yields. The demand for high-quality cacao products is expected to rise due to advancing technology in the present. Pre-harvesting needs to provide optimal identification of which amongst the pods are ripened enough and ready for the next stage of the cacao process. This paper recommends a technique to determine the ripeness of cacao. Nine hundred thirty-three cacao samples were used to collect thumping audio data at five different pod's exocarp locations. Each sound file is 1 second long, creating 4665 cacao sound file datasets at 16kHz sample rate and 16-bit audio bit depth. The process of the Mel-Frequency Cepstral Coefficient Spectogram was then applied to extract recognizable features for the training process. The deep learning method integrated was a convolutional neural network (CNN) to classify the cacao sound successfully. The experimental design model's output exhibits an accuracy of 97.50 % for the training data and 97.13 % for the validation data. While the overall accuracy mean of the classification system is 97.46 %, whether the cacao is unripe or ripe.

Purpose: Positional obstructive sleep apnea (OSA) is prevalent. We hypothesized that by incorporating positional therapy into a diagnosis-treatment algorithm for OSA it would frequently be prescribed as an appropriate first-line therapy. Methods: Fifty-nine members (45 males, 49±9 yrs, BMI 35.2±5.6 kg/m2) of the Law Enforcement Health Benefits (LEHB), Inc. of Philadelphia with clinically suspected OSA were evaluated. Patients completed an Epworth Sleepiness Scale (ESS) questionnaire and a home sleep test (HST). Patients diagnosed with positional OSA (non-supine apnea-hypopnea index [AHI] < 5 events/hr) were offered positional therapy. A cost comparison to continuous positive airway pressure (CPAP) therapy was performed. Results: Fifty-four (92%) of the patients (43 males, 49±9 yrs, BMI 35.2±5.3 kg/m2) had OSA on their HST (AHI 24.2±20.1 events/hr). Sixteen (30%) patients had positional OSA. Compared to non-positional patients, patients with positional OSA were less heavy (32.4±5.1 vs. 36.4±5.1 kg/m2, respectively [p=0.009]), less sleepy (ESS 8±5 vs. 12±5, respectively [p=0.009]), and had less severe OSA (AHI 10.4±4.3 vs. 30.0±21.3 events/hr, respectively [p

This article examines the political power of the church, state, and local elite in the context of the local elections, particularly the elections of the gobernadorcillo, in the Province of Tayabas from 1846 to 1895. Contained in the laws, decrees, and circulars of the Spanish government were the electoral process and method for the election of the gobernadorcillo. The election laws that will be discussed in this article are the Ordenanzas de Buen Gobierno de 1768; Circular de 5 de Octubre de 1847; and Real Decreto de Mayo 19 de 1893. This research will also discuss how the Spanish government instituted electoral reforms to prevent the abuse of power from the church and state. Part of the reform in the electoral process was to preserve the balance of power which was implemented through the political system called “check and balance”.

While much is known about acute infection pathogenesis, the understanding of chronic infections has lagged. Here we sought to identify the genes and functions that mediate fitness of the pathogen Pseudomonas aeruginosa in chronic wound infections, and to better understand the selective environment in wounds. We found that clinical isolates from chronic human wounds were frequently defective in virulence functions and biofilm formation, and that many virulence and biofilm formation genes were not required for bacterial fitness in experimental mouse wounds. In contrast, genes involved in anaerobic growth, some metabolic and energy pathways, and membrane integrity were critical. Consistent with these findings, the fitness characteristics of some wound impaired-mutants could be represented by anaerobic, oxidative, and membrane-stress conditions ex vivo, and more comprehensively by high-density bacterial growth conditions, in the absence of a host. These data shed light on the bacterial functions needed in chronic wound infections, the nature of stresses applied to bacteria at chronic infection sites, and suggest therapeutic targets that might compromise wound infection pathogenesis.

ABSTRACT While much attention has been focused on acquired antibiotic resistance genes, chromosomal mutations may be most important in chronic infections where isolated, persistently infecting lineages experience repeated antibiotic exposure. Here, we used experimental evolution and whole-genome sequencing to investigate chromosomally encoded mutations causing aztreonam resistance in Pseudomonas aeruginosa and characterized the secondary consequences of resistance development. We identified 19 recurrently mutated genes associated with aztreonam resistance. The most frequently observed mutations affected negative transcriptional regulators of the mexAB-oprM efflux system and the target of aztreonam, ftsI. While individual mutations conferred modest resistance gains, high-level resistance (1,024 µg/ml) was achieved through the accumulation of multiple variants. Despite being largely stable when strains were passaged in the absence of antibiotics, aztreonam resistance was associated with decreased in vitro growth rates, indicating an associated fitness cost. In some instances, evolved aztreonam-resistant strains exhibited increased resistance to structurally unrelated antipseudomonal antibiotics. Surprisingly, strains carrying evolved mutations which affected negative regulators of mexAB-oprM (mexR and nalD) demonstrated enhanced virulence in a murine pneumonia infection model. Mutations in these genes, and other genes that we associated with aztreonam resistance, were common in P. aeruginosa isolates from chronically infected patients with cystic fibrosis. These findings illuminate mechanisms of P. aeruginosa aztreonam resistance and raise the possibility that antibiotic treatment could inadvertently select for hypervirulence phenotypes. IMPORTANCE Inhaled aztreonam is a relatively new antibiotic which is being increasingly used to treat cystic fibrosis patients with Pseudomonas aeruginosa airway infections. As for all antimicrobial agents, bacteria can evolve resistance that decreases the effectiveness of the drug; however, the mechanisms and consequences of aztreonam resistance are incompletely understood. Here, using experimental evolution, we have cataloged spontaneous mutations conferring aztreonam resistance and have explored their effects. We found that a diverse collection of genes contributes to aztreonam resistance, each with a small but cumulative effect. Surprisingly, we found that selection for aztreonam resistance mutations could confer increased resistance to other antibiotics and promote hypervirulence in a mouse infection model. Our study reveals inherent mechanisms of aztreonam resistance and indicates that aztreonam exposure can have unintended secondary effects.

To avoid the high cost and arduous effort usually associated with field analysis of Wireless Sensor Network (WSN), Modeling and Simulation (M&S ) is used to predict the behavior and performance of the network. However, the simulation models utilized to imitate real life networks are often used for general purpose. Therefore, they are less likely to provide accurate predictions for different real life networks. In this paper, a comparison methodology based on hypothesis testing is proposed to evaluate and compare simulation output versus real-life network measurements. Performance related parameters such as traffic generation rates and goodput rates for a small WSN are considered. To execute the comparison methodology, a "Comparison Tool", composed of MATLAB scripts is developed and used. The comparison tool demonstrates the need for model verification and the analysis of good agreements between the simulation and empirical measurements.

Julie Steelandt,1 Damien Salmon,1,2 Elodie Gilbert,1 Eyad Almouazen,3 François NR Renaud,4 Laurène Roussel,1 Marek Haftek,5 Fabrice Pirot1,2 1University Claude Bernard Lyon 1, Faculty of Pharmacy, Fundamental, Clinical and Therapeutic Aspects of Skin Barrier Function, FRIPharm, Laboratoire de Pharmacie Galénique Industrielle, 2Hospital Pharmacy, FRIPharm, Hospital Edouard Herriot, Hospices Civils de Lyon, 3Laboratoire d’Automatique et de Génie des Procédés, University Claude Bernard Lyon 1, 4University Claude Bernard Lyon 1, UMR CNRS 5510/MATEIS, 5University Claude Bernard Lyon 1, Faculty of Pharmacy, Fundamental, Clinical and Therapeutic Aspects of Skin Barrier Function, FRIPharm, Laboratoire de Dermatologie, Lyon, France Abstract: Skin and mucosal infections constitute recurrent pathologies resulting from either inappropriate antiseptic procedures or a lack of efficacy of antimicrobial products. In this field, nanomaterials offer interesting antimicrobial properties (eg, long-lasting activity; intracellular and tissular penetration) as compared to conventional products. The aim of this work was to produce, by a new solvent-free process, a stable and easily freeze-dryable chlorhexidine-loaded polymeric nanocapsule (CHX-NC) suspension, and then to assess the antimicrobial properties of nanomaterials. The relevance of the process and the physicochemical properties of the CHX-NCs were examined by the assessment of encapsulation efficiency, stability of the nanomaterial suspension after 1 month of storage, and by analysis of granulometry and surface electric charge of nanocapsules. In vitro antimicrobial activities of the CHX-NCs and chlorhexidine digluconate solution were compared by measuring the inhibition diameters of two bacterial strains (Escherichia coli and Staphylococcus aureus) and one fungal strain (Candida albicans) cultured onto appropriate media. Based on the findings of this study, we report a new solvent-free process for the production of nanomaterials exhibiting antimicrobial activity, suitable stability, and easily incorporable as a new ingredient in various pharmaceutical products. Keywords: nanomaterial, nanocapsules, antiseptic, chlorhexidine, solvent-free process

Purpose. We hypothesized that socioeconomic factors and a language barrier would impact adherence with continuous positive airway pressure (CPAP) among Hispanics with obstructive sleep apnea (OSA). Methods. Patients with OSA who were prescribed CPAP for at least 1 year and completed a questionnaire evaluating demographic data, socioeconomic status, and CPAP knowledge and adherence participated in the study. Results. Seventy-nine patients (26 males; 53±11 yrs; body mass index (BMI)=45±9 kg/m2) with apnea-hypopnea index (AHI) 33±30 events/hr completed the study. Included were 25 Hispanics, 39 African Americans, and 15 Caucasians, with no difference in age, AHI, CPAP use, or BMI between the groups. While there was a difference in educational level (P=0.006), income level (P

The challenge of mothering while pursuing an academic career is the most significant obstacle to women's success. However, there is a lack of research examining how being a woman who intensively mothers co-exist with her autonomous subjectivity as an academic. In this qualitative study, academic mothers adhere both to an intensive mothering ideology and the ideal worker construct reified in neo-liberalised academic culture. We argue that these women negotiate the co-existence of these subjectivities from within a 'new' maternal subjectivity. These academic women are not victims of the patriarchal norms of the academy or the ideological constraints of intensive mothering. Instead, they actively negotiate institutional and ideological constraints in a way that incorporates their autonomous subjectivity and their maternal subjectivity.

Context. Since 2018, the ESPRESSO spectrograph at the VLT has been hunting for planets in the southern skies via the radial velocity (RV) method. One of its goals is to follow up on candidate planets from transit surveys such as the TESS mission, with a particular focus on small planets for which ESPRESSO's RV precision is vital. Aims. We aim to confirm and characterise, in detail, three super-Earth candidate transiting planets from TESS using precise RVs from ESPRESSO. Methods. We analysed photometry from TESS and ground-based facilities, high-resolution imaging, and RVs from ESPRESSO, HARPS, and HIRES, to confirm and characterise three new planets: TOI-260 b, transiting a late K dwarf, and TOI-286 b and c, orbiting an early K dwarf. We also updated the parameters for the known super-Earth TOI-134 b (L 168-9 b), which is hosted by an M dwarf. Results. TOI-260 b has a 13.475853−0.000011+0.000013 d period, 4.23 ± 1.60 M⊕ mass, and 1.71 ± 0.08 R⊕ radius. For TOI-286 b we find a 4.5117244−0.0000027+0.0000031 d period, 4.53 ± 0.78 M⊕ mass, and 1.42 ± 0.10 R⊕ radius; for TOI-286 c, we find a 39.361826−0.000081+0.000070 d period, 3.72 ± 2.22 M⊕ mass, and 1.88 ± 0.12 R⊕ radius. For TOI-134 b we obtain a 1.40152604−0.00000082+0.00000074 d period, 4.07 ± 0.45 M⊕ mass, and 1.63 ± 0.14 R⊕ radius. Circular models are preferred for all the planets, although for TOI-260 b the eccentricity is not well constrained. We computed bulk densities and placed the planets in the context of composition models. Conclusions. TOI-260 b lies within the radius valley, and is most likely a rocky planet. However, the uncertainty on the eccentricity and thus on the mass renders its composition hard to determine. TOI-286 b and c span the radius valley, with TOI-286 b lying below it and having a likely rocky composition, while TOI-286 c is within the valley, close to the upper border, and probably has a significant water fraction. With our updated parameters for TOI-134 b, we obtain a lower density than previous findings, giving a rocky or Earth-like composition. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor (TNF) inhibitors are becoming more common in the treatment of moderate-to-severe chronic plaque psoriasis. These medications have a low incidence of serious adverse events and are generally considered safe; however, they do make patients more susceptible to tuberculosis (TB) infection both through latent reactivation and primary infection. We describe a case of a patient who had an initial negative tuberculin skin test (TST), began TNF inhibitor therapy, and then 11 years later was diagnosed with active TB. After the initial screening, the patient did not have any subsequent screenings for TB and no apparent change to his TB risk status. TB is still common in many areas of the United States and travel is not necessary to be exposed. Patients on TNF inhibitors that develop active TB have increased morbidity and mortality than those who are not. It is necessary that dermatologists limit the risk of TB to patients by screening them before initiation and annually when they are on the TNF inhibitor.

In the production of biological therapeutics such as monoclonal antibodies (mAbs), ultrafiltration and diafiltration (UF/DF) are widely regarded as effective downstream processing steps capable of removing process equipment related leachables (PERLs) introduced upstream of the UF/DF step. However, clearance data available in the literature are limited to species with low partition coefficients (log P) such as buffer ions, hydrophilic organic compounds, and some metal ions. Additional data for a wide range of PERLs including hydrophobic compounds and elemental impurities are needed to establish meaningful, comprehensive safety risk assessments. Herein, we report the results from studies investigating the clearance of seven different organic PERLs representing a wide range of characteristics (i.e., log P (−0.3 to 18)), and four model elements with different chemical properties spiked into a mAb formulation at 10 ppm and analyzed during clearance using gas chromatography–mass spectrometry (GC–MS), liquid chromatography‐photodiode‐array‐mass spectrometry (LC‐PDA‐MS), and inductively coupled plasma mass spectrometry (ICP‐MS). The clearance data showed ideal clearance and sieving of spiked organic PERLs with log P < 4, partial clearance of PERLs with 4 < log P < 9, and poor clearance of highly hydrophobic PERLs (log P > 9) after nine diafiltration volumes (DVs). Supplemental clearance studies on seven additional PERLs present at much lower concentration levels (0.1–1.5 ppm) in the mAb formulation upstream of UF/DF and three PERLs associated with the tangential flow filtration (TFF) equipment also demonstrated the similar correlations between log P and % clearance. For model elements, the findings suggest that UF/DF in general provides ideal clearance for elements. Evidence showed that the UF/DF process does not only help mitigate leachables risk from PERLs introduced upstream of UF/DF, but also from the TFF operation itself as all three TFF‐related PERLs were effectively cleared. Overall, the UF/DF clearance presented in this work demonstrated whereas highly hydrophobic PERLs and elements that exist as charged species, particularly transition metal ions, may not be as effectively cleared and thus warrant further risk assessment; hydrophilic and some hydrophobic PERLs (log P < 4) are indeed well‐cleared and thus present a lower overall safety risk. [ABSTRACT FROM AUTHOR]