Definition of tachycardia for risk stratification of pulmonary embolism.

Tachycardia is a reliable predictor of adverse outcomes in normotensive patients with acute pulmonary embolism (PE). However, different prognostic relevant heart rate thresholds have been proposed. The aim of the study was to investigate the prognostic performance of different thresholds used for defining tachycardia in normotensive PE patients.We performed a post-hoc analysis of normotensive patients with confirmed PE consecutively included in a single-centre and a multi-centre registry. An adverse outcome was defined as PE-related death, need for mechanical ventilation, cardiopulmonary resuscitation or administration of catecholamines.Of 1567 patients (median age: 72 [IQR, 59-79] years; females: 46.1%) included in the analysis, 78 patients (5.0%) had an in-hospital adverse outcome. The rate of an adverse outcome was higher in patients with a heart rate ≥100 bpm (7.6%) and ≥110 bpm (8.3%) compared to patients with a heart rate100 bpm (3.0%). A heart rate ≥100 bpm and ≥110 bpm was associated with a 2.7 (95% CI 1.7-4.3) and 2.4-fold (95% CI 1.5-3.7) increased risk for an adverse outcome, respectively. Receiver operating characteristics analysis revealed a similar area under the curve with regard to an adverse outcome for all scores and algorithm (ESC 2019 algorithm, modified FAST and Bova score) if calculated with a heart rate threshold of ≥100 bpm or of ≥110 bpm.Defining tachycardia by a heart rate ≥100 bpm is sufficient for risk stratification of normotensive patients with acute PE. The use of different heart rate thresholds for calculation of scores and algorithm does not appear necessary

Phenolic compounds and aroma-impact odorants in herb liqueurs elaborated by maceration of aromatic and medicinal plants in grape marc distillates

Twenty-eight commercial herb liqueurs, elaborated by maceration of aromatic and medicinal plants in grape marc distillate, were analysed. Thirty-two volatile compounds were identified and quantified by gas chromatographymass spectrometry, whereas seven phenols were determined by high-performance liquid chromatography with UV detection. All compounds showed significant differences among the samples analysed as consequence of the initial composition of the distillate and the plants and spices used in the liqueur elaboration. Of the 32 volatile compounds identified, 18 were considered to be impact odorants (odour activity value ?1) and these were classified into six odorant series. Spice, fruity and floral were the series that contributed the most to the aroma profile of the evaluated liqueurs. A first principal components analysis (PCA) was performed on the concentration of the seven phenols and these accounted for 75.37% of the total variance and a second PCA was performed on the concentration of the 18 impact odorants and these accounted for 60.96% of the total variance; allowing for the classification of the liqueur samples into three different groups.We are grateful to the Spanish Ministry of Economy and Competitiveness for the financial support of this work (project CTQ201571436-C2-1-R), which has partial financial support from the FEDER funds of the European Union. José Manuel Salgado was supported by the grant SFRH/BPD/84440/2012 from Fundação para a Ciência e Tecnologia - FCT, Portugal

Single DermaVir Immunization: Dose-Dependent Expansion of Precursor/Memory T Cells against All HIV Antigens in HIV-1 Infected Individuals

BACKGROUND: The GIHU004 study was designed to evaluate the safety and immunogenicity of three doses of DermaVir immunization in HIV-infected subjects on fully suppressive combination antiretroviral therapy (cART). METHODOLOGY/PRINCIPAL FINDINGS: This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted to epidermal Langerhans cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes. Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining lymph node via ∼8 million Langerhans cells located in 80 cm(2) epidermis area. The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir-associated side effects were mild, transient and not dose-dependent. Boosting of HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was detected against several antigens in every subject of the medium dose cohort. The striking result was the dose-dependent expansion of HIV-specific precursor/memory T cells with high proliferation capacity. In low, medium and high dose cohorts this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year, respectively, compared to baseline. CONCLUSIONS/SIGNIFICANCE: Single immunization with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV-infected individuals. Based on the potent induction of Gag, Tat and Rev-specific memory T cells, especially in the medium dose cohort, we speculate that DermaVir boost T cell responses specific to all the 15 HIV antigens expressed from the single DNA. For durable immune reactivity repeated DermaVir immunization might be required since the frequency of DermaVir-boosted HIV-specific memory T cells decreased during the 48-week follow up. TRIAL REGISTRATION: ClinicalTrial.gov NCT00712530

The DUNE far detector vertical drift technology. Technical design report

DUNE is an international experiment dedicated to addressing some of the questions at the forefront of particle physics and astrophysics, including the mystifying preponderance of matter over antimatter in the early universe. The dual-site experiment will employ an intense neutrino beam focused on a near and a far detector as it aims to determine the neutrino mass hierarchy and to make high-precision measurements of the PMNS matrix parameters, including the CP-violating phase. It will also stand ready to observe supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector implements liquid argon time-projection chamber (LArTPC) technology, and combines the many tens-of-kiloton fiducial mass necessary for rare event searches with the sub-centimeter spatial resolution required to image those events with high precision. The addition of a photon detection system enhances physics capabilities for all DUNE physics drivers and opens prospects for further physics explorations. Given its size, the far detector will be implemented as a set of modules, with LArTPC designs that differ from one another as newer technologies arise. In the vertical drift LArTPC design, a horizontal cathode bisects the detector, creating two stacked drift volumes in which ionization charges drift towards anodes at either the top or bottom. The anodes are composed of perforated PCB layers with conductive strips, enabling reconstruction in 3D. Light-trap-style photon detection modules are placed both on the cryostat's side walls and on the central cathode where they are optically powered. This Technical Design Report describes in detail the technical implementations of each subsystem of this LArTPC that, together with the other far detector modules and the near detector, will enable DUNE to achieve its physics goals

Validation of a fast prognostic score for risk stratification of normotensive patients with acute pulmonary embolism

Background: Recent studies demonstrate an improved prognostic performance of the 2014 European Society of Cardiology (ESC) algorithm for risk stratification of patients with pulmonary embolism (PE) compared to the 2008 ESC algorithm. The modified FAST and Bova scores appear especially helpful to identify PE patients at intermediate-high risk. Methods: We validated the prognostic performance of the modified FAST score compared to other scores for risk stratification in a post-hoc analysis of 868 normotensive PE patients included in the prospective Italian Pulmonary Embolism Registry. In-hospital adverse outcome was defined as PE-related death, mechanical ventilation, cardiopulmonary resuscitation or administration of catecholamines. Results: Overall, 27 patients (3.1%) had an adverse outcome and 32 patients (3.7%) died. The rate of an adverse outcome was highest in the intermediate-high risk classes of the 2019 ESC algorithm (7.5%) and the modified FAST score (5.3%) while the Bova score failed to discriminate between intermediate-low and intermediate-high-risk patients. Patients classified as intermediate-high risk by the 2019 ESC algorithm (Odds Ratio [OR], 4.2 [95% CI, 1.9–9.0]) and modified FAST score (OR, 2.8 [1.3–6.2]) had a higher risk of an adverse outcome compared to patients classified by the Bova score (OR, 1.6 [0.7–3.7]). The c-index was higher for the 2019 ESC algorithm and the modified FAST score (AUC, 0.69 [0.58–0.79] and 0.67 [0.59–0.76]) compared to the Bova score (AUC, 0.64 [0.55–0.73]). Conclusions: The 2019 ESC algorithm provided the best prognostic performance, but also the modified FAST score accurately stratified normotensive PE patients in different risk classes while the Bova score failed to identify patients at highest risk

Effects of oral contraceptives on peak exercise capacity.

There is evidence that perceived peer eating norms can influence dietary behaviour. This cross-sectional study examined whether certain personality traits increase the likelihood that personal eating habits are similar to perceived peer eating habits. We assessed frequency of consumption of sugar-sweetened soda (SSS) and sweet pastries (SP), as well as perceived peer descriptive eating norms for SSS and SP in a group of 1056 young adults. We examined whether individual differences in the need for social acceptance and self-control moderated whether participants were likely to display similar dietary habits to their peers. Perceived peer eating norms for SSS and SP predicted frequency of consumption; believing that one’s peers frequently consumed SSS and SP was associated with increased personal consumption for both. Individuals with low self-control, as opposed to high self-control, were more likely to adhere to peer norms for SP, but not for SSS. Trait social acceptance needs did not significantly moderate similarity between peer norms and personal consumption for either SSS or SP. The extent to which young adults adhere to descriptive peer dietary norms may depend upon self-control, whereby individuals with low self-control are less able to inhibit social influence of descriptive peer norms on dietary behaviour