The effects of rhythm and melody on auditory stream segregation

Whilst many studies have assessed the efficacy of similarity-based cues for auditory stream segregation, much less is known about whether and how the larger-scale structure of sound sequences support stream formation and the choice of sound organization. Two experiments investigated the effects of musical melody and rhythm on the segregation of two interleaved tone sequences. The two sets of tones fully overlapped in pitch range, but differed from each other in interaural time and intensity. Unbeknownst to the listener, separately, each of the interleaved sequences was created from the notes of a different song. In different experimental conditions, the notes and/or their timing could either follow those of the songs, or they could be scrambled or, in case of timing, set to be isochronous. Listeners were asked to continuously report whether they heard a single coherent sequence (integrated) or two concurrent streams (segregated). Although temporal overlap between tones from the two streams proved to be the strongest cue for stream segregation, significant effects of tonality and familiarity with the songs were also observed. These results suggest that the regular temporal patterns are utilized as cues in auditory stream segregation and that long-term memory is involved in this process

Sr/Ca ratios and oxygen isotopes from sclerosponges: Temperature history of the Carribean mixed layer and thermocline during the Little Ice Age

We investigate aragonitic skeletons of the Caribbean sclerosponge Ceratoporella nicholsoni from Jamaica, 20 m below sea level (mbsl), and Pedro Bank, 125 mbsl. We use d18O and Sr/Ca ratios as temperature proxies to reconstruct the Caribbean mixed layer and thermocline temperature history since 1400 A.D. with a decadal time resolution. Our age models are based on U/Th dating and locating of the radiocarbon bomb spike. The modern temperature difference between the two sites is used to tentatively calibrate the C. nicholsoni Sr/Ca thermometer. The resulting calibration points to a temperature sensitivity of Sr/Ca in C. nicholsoni aragonite of about -0.1 mmol/mol/K. Our Sr/Ca records reveal a pronounced warming from the early 19th to the late 20th century, both at 20 and 125 mbsl. Two temperature minima in the shallow water record during the late 17th and early 19th century correspond to the Maunder and Dalton sunspot minima, respectively. Another major cooling occurred in the late 16th century and is not correlatable with a sunspot minimum. The temperature contrast between the two sites decreased from the 14th century to a minimum in the late 17th century and subsequently increased to modern values in the early 19th century. This is interpreted as a long-term deepening and subsequent shoaling of the Caribbean thermocline. The major trends of the Sr/Ca records are reproduced in both specimens but hardly reflected in the d18O records

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial.

BACKGROUND Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. METHODS This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m2 BCNU on day -6), in BendaEAM, BCNU was replaced by 200 mg/m2 bendamustine given on days -7 and -6. Eligible patients were aged 18-75 years and had mantle cell lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma in first or second remission or chemosensitive relapse. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine reduces lung toxicity, defined as a decrease of the diffusion capacity of the lung for carbon monoxide by at least 20% at three months after ASCT. Data analyses were performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02278796, and is complete. FINDINGS Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. INTERPRETATION Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. FUNDING Mundipharma

Neoadjuvant Chemotherapy Modulates the Immune Microenvironment in Metastases of Tubo-Ovarian High-Grade Serous Carcinoma

This research was funded by Swiss Cancer League (BIL KLS-2883-02-2012), the European Research Council (ERC322566), Cancer Research UK (A16354), and Barts and The London Charity (467/1307)

Annual- to interannual temperature variability in the Caribbean during the Maunder Sunspot minimum

We reconstruct Caribbean seawater temperatures from sclerosponge Sr/Ca ratios using a specimen of Ceratoporella nicholsoni that grew at 20 m below sea level in a reef cave at Jamaica. We sample the time interval from 1620 to 1745 A.D. with almost monthly resolution. This interval includes the Maunder sunspot minimum, one of the coldest periods of the Little Ice Age. Reconstructed annual temperature amplitudes are on the order of about 1°C. The mean growth rate calculated from the annual Sr/Ca variations corresponds perfectly with U-Th-based growth rates. We find that the interannual climate variability is determined by El Niño–Southern Oscillation and by a decadal signal, most likely originating from the tropical North Atlantic. On a multidecadal timescale the Maunder Minimum is characterized by a 1°–2°C cooling and reduced amplitudes of the interannual and decadal temperature variations

Effects of serelaxin in patients with acute heart failure

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure. Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days. Results: A total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups. Conclusions: In this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778. opens in new tab.

Advancing the contributions of European stakeholders in farming systems to transitions to agroecology

The concept of a ‘just transition’ is gaining traction in international policy discourses. It has particular significance in relation to achieving net zero greenhouse gas emissions and the need for ensuring rights and responsibilities of all actors in transitions to agroecological farming systems. Research plays an important role in accompanying this transformation. It explores pathways for more sustainable and fair food systems, barriers to them being achieved, and where and what risks arise for communities of interest and of place. Researchers and practitioners across levels and sectors were brought together in H2020 projects LIFT and UNISECO using processes of stakeholder engagement. Both projects analysed the perceptions of actors towards agroecological farming, and their active involvement in the transitions required. This article summarises lessons learnt regarding multi‐actor engagement in different participatory settings in both projects, including a Multi‐Actor Platform approach, Q method, DELPHI and Hybrid forum workshops. The interactions involved several hundred actors from 18 countries across Europe. The article reflects on implications of the Covid‐19 pandemic on the processes and effectiveness of multi‐actor engagement, and assessments of the impacts on the empowerment of the actors. The findings are contextualised by contemporary European Union and national policy objectives of tackling climate change, the loss of biodiversity, and inequalities

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome

© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.The International Takotsubo Registry was supported by the Biss Davies Charitable Trust. Dr. Scheitz has been supported by the Corona Foundation. Dr. Templin has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme and the Swiss Heart Foundation.info:eu-repo/semantics/publishedVersio

Prognostic impact of acute pulmonary triggers in patients with Takotsubo syndrome : new insights from the International Takotsubo Registry

© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License.Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002). Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.C. T. has been supported by the H.H. Sheikh Khalifa binHamad Al-Thani Research Programme and the Swiss HeartFoundation. The InterTAK Registry is supported by the BissDavies Charitable Trust. L. S. M. has been supported by EUHORIZON 2020(SILICOFCM ID777204)info:eu-repo/semantics/publishedVersio