The place of vericiguat in the landscape of treatment for heart failure with reduced ejection fraction

The significant morbidity and mortality associated with heart failure with reduced (HFrEF) or preserved ejection fraction (HFpEF) justify the search for novel therapeutic agents. The nitric oxide (NO)–soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function. This pathway is disrupted in HF resulting in decreased protection against myocardial injury. The sGC activator cinaciguat increases cGMP levels by direct, NO-independent activation of sGC, and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and then reduced NO levels, but this comes at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, and then exert a more physiological action. The phase 3 VICTORIA trial found that vericiguat is safe and effective in patients with HFrEF and recent HF decompensation. Therefore, adding vericiguat may be considered in individual patients with HFrEF, particularly those at higher risk of HF hospitalization; the efficacy of the sacubitril/valsartan-vericiguat combination in HFrEF is currently unknown

Indications of beta-adrenoceptor blockers in Takotsubo syndrome and theoretical reasons to prefer agents with vasodilating activity

Takotsubo syndrome (TTS) is estimated to account for 1–3% of all patients presenting with suspected ST-segment elevation myocardial infarction. A sudden surge in sympathetic nervous system is considered the cause of TTS. Nonetheless, no specific recommendations have been provided regarding β-blocking therapy. Apart from specific contra-indications (severe LV dysfunction, hypotension, bradycardia and corrected QT interval >500 ms), treatment with a β-blocker seems reasonable until full recovery of LV ejection fraction, though evidence is limited to a few animal studies, case reports or observational studies. In this review, we will reappraise the rationale for β-blocker therapy in TTS and speculate on the pathophysiologic basis for preferring non-selective agents with vasodilating activity over β1-selective drugs

Analysis of Snow Cover in the Sibillini Mountains in Central Italy

Research on solid precipitation and snow cover, especially in mountainous areas, suffers from problems related to the lack of on-site observations and the low reliability of measurements, which is often due to instruments that are not suitable for the environmental conditions. In this context, the study area is the Monti Sibillini National Park, and it is no exception, as it is a mountainous area located in central Italy, where the measurements are scarce and fragmented. The purpose of this research is to provide a characterization of the snow cover with regard to maximum annual snow depth, average snow depth during the snowy period, and days with snow cover on the ground in the Monti Sibillini National Park area, by means of ground weather stations, and also analyzing any trends over the last 30 years. For this research, in order to obtain reliable snow cover data, only data from weather stations equipped with a sonar system and manual weather stations, where the surveyor goes to the site each morning and checks the thickness of the snowpack and records, it were collected. The data were collected from 1 November to 30 April each year for 30 years, from 1991 to 2020; six weather stations were taken into account, while four more were added as of 1 January 2010. The longer period was used to assess possible ongoing trends, which proved to be very heterogeneous in the results, predominantly negative in the case of days with snow cover on the ground, while trends were predominantly positive for maximum annual snow depth and distributed between positive and negative for the average annual snow depth. The shorter period, 2010–2022, on the other hand, ensured the presence of a larger number of weather stations and was used to assess the correlation and presence of clusters between the various weather stations and, consequently, in the study area. Furthermore, in this way, an up-to-date nivometric classification of the study area was obtained (in terms of days with snow on the ground, maximum height of snowpack, and average height of snowpack), filling a gap where there had been no nivometric study in the aforementioned area. The interpolations were processed using geostatistical techniques such as co-kriging with altitude as an independent variable, allowing fairly precise spatialization, analyzing the results of cross-validation. This analysis could be a useful tool for hydrological modeling of the area, as well as having a clear use related to tourism and vegetation, which is extremely influenced by the nivometric variables in its phenology. In addition, this analysis could also be considered a starting point for the calibration of more recent satellite products dedicated to snow cover detection, in order to further improve the compiled climate characterizatio

Quality of life assessment in amyloid transthyretin (ATTR) amyloidosis

Background: Amyloid transthyretin (ATTR) amyloidosis is caused by the systemic deposition of transthyretin molecules, either normal (wild-type ATTR, ATTRwt) or mutated (variant ATTR, ATTRv). ATTR amyloidosis is a disease with a severe impact on patients’ quality of life (QoL). Nonetheless, limited attention has been paid to QoL so far, and no specific tools for QoL assessment in ATTR amyloidosis currently exist. QoL can be evaluated through patient-reported outcome measures (PROMs), which are completed by patients, or through scales, which are compiled by clinicians. The scales investigate QoL either directly or indirectly, i.e., by assessing the degree of functional impairment and limitations imposed by the disease. Design: Search for the measures of QoL evaluated in phase 2 and phase 3 clinical trials on ATTR amyloidosis. Results: Clinical trials on ATTR amyloidosis have used measures of general health status, such as the Short Form 36 Health Survey (SF-36), or tools developed in other disease settings such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) or adaptations of other scales such as the modified Neuropathy Impairment Score +7 (mNIS+7). Conclusions: Scales or PROMs for ATTR amyloidosis would be useful to better characterize newly diagnosed patients and to assess disease progression and response to treatment. The ongoing ITALY (Impact of Transthyretin Amyloidosis on Life qualitY) study aims to develop and validate 2 PROMs encompassing the whole phenotypic spectrum of ATTRwt and ATTRv amyloidosis, that might be helpful for patient management and may serve as surrogate endpoints for clinical trials

LIPS vs MOSA: a Replicated Empirical Study on Automated Test Case Generation

Replication is a fundamental pillar in the construction of scientific knowledge. Test data generation for procedural programs can be tackled using a single-target or a many-objective approach. The proponents of LIPS, a novel single-target test generator, conducted a preliminary empirical study to compare their approach with MOSA, an alternative many-objective test generator. However, their empirical investigation suffers from several external and internal validity threats, does not consider complex programs with many branches and does not include any qualitative analysis to interpret the results. In this paper, we report the results of a replication of the original study designed to address its major limitations and threats to validity. The new findings draw a completely different picture on the pros and cons of single-target vs many-objective approaches to test case generation

Action-based recommendation in pull-request development

Pull requests (PRs) selection is a challenging task faced by integrators in pull-based development (PbD), with hundreds of PRs submitted on a daily basis to large open-source projects. Managing these PRs manually consumes integrators' time and resources and may lead to delays in the acceptance, response, or rejection of PRs that can propose bug fixes or feature enhancements. On the one hand, well-known platforms for performing PbD, like GitHub, do not provide built-in recommendation mechanisms for facilitating the management of PRs. On the other hand, prior research on PRs recommendation has focused on the likelihood of either a PR being accepted or receive a response by the integrator. In this paper, we consider both those likelihoods, this to help integrators in the PRs selection process by suggesting to them the appropriate actions to undertake on each specific PR. To this aim, we propose an approach, called CARTESIAN (aCceptance And Response classificaTion-based requESt IdentificAtioN) modeling the PRs recommendation according to PR actions. In particular, CARTESIAN is able to recommend three types of PR actions: accept, respond, and reject. We evaluated CARTESIAN on the PRs of 19 popular GitHub projects. The results of our study demonstrate that our approach can identify PR actions with an average precision and recall of about 86%. Moreover, our findings also highlight that CARTESIAN outperforms the results of two baseline approaches in the task of PRs selection

Social stratification, secondary school tracking and university enrolment in Italy

This paper looks at class inequality in the probability of enrolling in university in Italy from a long-term perspective. Given that Italian higher secondary education is tracked, it studies how tracking interacts over time with class origin in the production of inequality of educational opportunities, thus contributing to the growing literature on the inequality effects of the qualitative, or horizontal, stratification of educational systems. The paper has thus two research questions. First, it asks whether class inequality in participation in higher education has changed over time; second, whether and how this change was influenced by the tracked structure of upper secondary school. Empirical analyses are based on data from the Italian Longitudinal Household Survey, a retrospective panel survey including detailed life-course information about a representative sample of the Italian population. In an educational transition framework, we analyse the association between social class, tracking and university enrolment, applying the Karlson/Holm/Breen decomposition method for logistic regression coefficients. We find increasing inequality in accessing university, and a change in the role of upper secondary track, whose mediating role between family background and university choice appears to have weakened over time

Condizione occupazionale e dinamiche familiari delle donne immigrate in Italia

Many studies assume all women to be tied movers and on the basis of this assumption often choose to drop all female migrants from the analysis. Even when this decision might have some reasons, geographical movements may have a strong impact on female participation in the labour market. The aim of this work is to analyse the employment condition of immigrant women in Italy. The research questions are: a) if migrant and natives women were identical in their basic characteristics, would the employment opportunities of the former still be worse than those of the latter? b) does this difference change on the basis of family migration dynamics? We use the EU-LFS data set to estimate a set of linear probability models, analysing both job quality and the employment decision. We found that there is a strong penalization in terms of probability of being employed only for tied-movers immigrant women. However, when we analyze whether the quality of job is good, we observe a strong difference between native and migrant women, independently from their family migration dynamics. Also the husband\u2019s occupational position matter. The employment penalty of migrant women is lower when the husband does not work or is in low-quality jobs. Nevertheless, also in this case, migrant women are still penalized in terms of probabilities of getting a good job, whichever the work condition of the husband or partner