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Abstract Convective Self‐Aggregation (CSA) is a common feature of idealized numerical simulations of the tropical atmosphere in Radiative‐Convective Equilibrium (RCE). However, at coarse grid resolution where deep convection is not fully resolved, the occurrence of this phenomenon is extremely sensitive to subgrid‐scale processes. This study examines the role of mixing and entrainment, provided by the turbulence model and the implicit numerical diffusion. The study compares the results of two models, WRF and SAM, by varying turbulence models, initial conditions, and horizontal spatial resolution. At a coarse grid resolution of 3 km, the removal of turbulent mixing prevents CSA in models with low numerical diffusivity but is preserved in models with high numerical diffusivity. When the horizontal grid resolution is refined to 1 km, CSA can only be achieved by increasing explicit turbulent mixing, even with a small amount of shallow clouds. Therefore, the sensitivity of CSA to horizontal grid resolution is not primarily caused by the decrease in shallow clouds. The analysis of the total water path spectrum suggests that the amplitude of initial humidity perturbations introduced by convection in the free troposphere is the key factor. This amplitude is regulated by turbulent mixing and diffusion at small scales. Prior to the onset of CSA, increased mixing makes updrafts more sensitive to the dryness of the free troposphere, which strengthens the moisture‐convection feedback. This leads to an increased distance between convective cores and a stronger humidity perturbation in the free troposphere, which can destabilize the RCE state.

Mediterranean tropical-like cyclones, called medicanes, present a multi-scale nature, and their track and intensity have been recognized as highly sensitive to large-scale atmospheric forcing and diabatic heating as represented by the physical parameterizations in numerical weather prediction. Here, we analyse the structure and investigate the predictability of medicanes with the aid of the European Centre for Medium-Range Weather Forecast (ECMWF) Integrated Forecast System (IFS) ensemble forecasting system with 25 perturbed members at 9 km horizontal resolution (compared with the 16 km operational resolution). The IFS ensemble system includes the representation of initial uncertainties from the ensemble data assimilation (EDA) and a recently developed uncertainty representation of the model physics with perturbed parameters (stochastically perturbed parameterizations, SPP). The focus is on three medicanes, Ianos, Zorbas, and Trixie, among the strongest in recent years. In particular, we have carried out separate ensemble simulations with initial perturbations, full physics SPP, with a reduced set of SPP, where only convection is perturbed to highlight the convective nature of medicanes and an operational ensemble combining the SPP and the initial perturbations. It is found that compared with the operational analysis and satellite rainfall data, the forecasts reproduce the tropical-like features of these cyclones. Furthermore, the SPP simulations compare to the initial-condition perturbation ensemble in terms of tracking, intensity, precipitation, and, more generally, in terms of ensemble skill and spread. Moreover, the study confirms that similar processes are at play in the development of the investigated three medicanes, in that the predictability of these cyclones is linked not only to the prediction of the precursor events (namely the deep cutoff low) but also to the interaction of the upper-level advected potential vorticity (PV) streamer with the tropospheric PV anomaly that is diabatically produced by latent heat.

Abstract The radiative‐convective equilibrium (RCE) of two models exhibiting convective aggregation has been compared. The goal of the work, following the suggestion from the RCE Model Intercomparison Project (RCEMIP), is to identify key parameters controlling self‐aggregation in RCE for both models, to discuss the processes controlled by these parameters and to underline the models similarities and differences. The two cloud resolving models studied, the SAM (System for Atmospheric Modeling) and the ARPS (Advanced Regional Prediction System), present similar statistics concerning precipitation, but different warming, and drying of the atmosphere, within the spread of the RCEMIP values. On the other hand, the two models show different strengths of the moisture feedback, due to the different saturation of the sub‐cloud layer. A saturated sub‐cloud layer in ARPS (which was not artificially imposed in the numerical setup) allows the localization of convection in moist regions, by weakening the negative influence of cold pools. Such a mechanism leads to a lower degree of aggregation (based on three organization metrics) and a weaker effect of the organized state on the average domain statistics in ARPS. Stronger cold pools in SAM, instead, help the creation of shallow clouds in dry regions, increasing the longwave feedback responsible for their expansion; while delocalizing convection in moist regions and therefore opposing high‐cloud radiative‐feedback. Further experiments are needed to generalize such findings to other RCEMIP models, also investigating the role of microphysics and turbulence schemes in regulating such mechanisms.

Aim of the present work was the instrumentation of a maxi scooter for the field collection of service loads acting on the scooter main components such as frame, fork, handlebar, rear frame and suspension. Service loads were collected on an instrumented Yamaha Tmax scooter equipped with 22 channels during a set of field tests that were representing a predefined road mix, covering a mileage of 270 km. Field load histories were used to develop an accelerated test procedure for the accelerated bench fatigue testing of a new model prototype whose mission was set to 50000 km. The acceleration procedure allowed a time reduction from 1600 hrs to 122 hrs bench equivalent testing. Both the benchmark scooter Tmax and a maxi-scooter prototype under development underwent the bench variable amplitude fatigue testing. The results of the fatigue tests on the prototype allowed to identify some critical bolted connections and to reduce some stress concentration features causing the appearance of small cracks that were found also after during 50000 km of driving tests.

The aim of this study was to assess the efficacy of Mézières method in improving trunk flexibility of the back muscles and balance in patients with Parkinson’s disease (PD). Materials and Methods. Thirty-six patients were randomized into 2 groups: the Mézières treatment group and the control group (home exercise group). The primary outcome was the improvement in balance per the Berg Balance Scale (BBS) and the trunk flexibility of the back for the anterior flexion trunk test. Also, we evaluated pain, gait balance for the Functional Gait Assessment (FGA), disease-related disability for the Modified Parkinson’s Activity Scale and the Unified Parkinson’s Disease Rating Scale (UPDRS), the quality of life, and the functional exercise capacity. All the measures were evaluated at baseline (T0), at the end of the rehabilitative program (T1), and at the 12-week follow-up (T2). Results. In the Mézières group, the BBS (p

Sjögren syndrome (SS) is an autoimmune disease of the exocrine glands, characterized by focal lymphocytic infiltration and destruction of these glands. Neurologic complications are quite common, mainly involving the peripheral nervous system (PNS). The most common central nervous system (CNS) manifestations are myelopathy and microcirculation vasculitis. However, specific diagnostic criteria for CNS SS are still lacking. We report two cases of primary SS in which the revealing symptom was cerebral venous thrombosis (CVT) in the absence of genetic or acquired thrombophilias.

Abstract Background Docetaxel in combination with two HER2-directed therapies, trastuzumab and pertuzumab, is the current standard frontline therapy for patients with metastatic HER2-positive breast cancer. Ado-trastuzumab (T-DM1), an antibody-drug conjugate of trastuzumab and a cytotoxic microtubule-inhibitory agent, emtansine, is approved in patients that have progressed with prior trastuzumab-based therapy. However, the benefit of T-DM1 in patients previously treated with pertuzumab therapy for metastatic breast cancer remains unclear. Methods We identified thirty-three adults with metastatic HER2-positive breast cancer treated between March 2013 and July 2018 with T-DM1 either as subsequent therapy after progression on a pertuzumab-based regimen (i.e., “pertuzumab-pretreated”) or without prior exposure to pertuzumab (i.e., “pertuzumab-naïve”). Collected data included patient demographics, treatment history, adverse events, and clinical outcomes. For both cohorts receiving T-DM1, the primary endpoint was PFS and secondary endpoints were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and T-DM1-related toxicity rate. Results Pertuzumab-pretreated patients (n = 23, with 21 evaluable for T-DM1 efficacy) had a median PFS of 9.5 months (95% CI: 2.9–NA), 1-year OS rate of 67.4% (95% CI: 50.0–90.9%) with an unreached median, ORR of 14.3% (95% CI: 3.0–36.3%), and CBR of 52.4% (95% CI: 29.8–74.3%), with none of these measures being statistically different than those estimated for the pertuzumab-naïve group (n = 10). Treatment with T-DM1 after prior pertuzumab exposure (median T-DM1 duration 2.9 months) resulted in no grade ≥ 3 adverse events. Conclusions In our cohort, prior exposure to pertuzumab did not significantly impact T-DM1’s clinical efficacy or safety profile as second- or later-line therapy in patients with metastatic HER2-positive breast cancer.

Even if the sensitivity of vegetation phenology to climate change has been accepted on global and continental scales, the correlation between global warming and phenotypic variability shows a modulated answer depending on altitude, latitude, and the local seasonal thermal trend. To connect global patterns of change with local effects, we investigated the impact of the observed signal of warming found in Central Italy on two different willow species, Salix acutifolia and Salix smithiana, growing in three phenological gardens of the International Phenological Gardens' network (IPG) located in different orographic positions. The time series of temperatures and phenological data for the period 2005-2018 were analysed first to find trends over time in the three gardens and then to correlate the recent local warming and the change in the two species phenology. The results confirmed the correlation between phenological trends and local trend of temperatures. In particular: budburst showed a trend of advancement of 1.4 days/year on average in all three gardens; flowering showed a divergent pattern between the gardens of either advancement of 1.0 days/year on average or delay of 1.1 days/year on average; while senescence showed a delay reaching even 3.3 days/year, although significant in only two gardens for both species. These trends were found to be correlated mainly with the temperatures of the months preceding the occurrence of the phase, with a shift in terms of days of the year (DOY) of the two species. Our conclusion is that the observed warming in Central Italy played a key role in controlling the phenophases occurrences of the two willow species, and that the orographic forcing leads to the different shift in DOY of phenophases (from 5 to 20 days) due to the local thermal forcing of the three phenological gardens., (© 2021. The Author(s).)

Background: Prolonged operating room turnover time erodes patient and employee satisfaction and value., Methods: Lean and value stream mapping was applied to three operating room teams at an academic health center in New York City, and a solution called Performance Improvement Team (PIT Crew) was piloted., Results: Overall, 10% of operating room turnover steps were considered nonvalued and were eliminated, and 25% of previously sequential steps were performed synchronously. Seven institutional dogmas were eliminated, and three hospital policies were changed. After 35 pilot turnovers, median operating room turnover time improved from 37 minutes (range, 26 to 167 minutes) in historic matched controls to 14 minutes (range, 10 to 45 minutes, p < 0.0001) for the PIT Crew. Cost of the PIT Crew was $1,298 daily, and estimated return on investment was $19,500 per day., Conclusions: Lean and value stream mapping identifies nonvalued steps in operating room turnover and affords opportunities for efficiency. Once institutional rules and dogma are changed, culture and workflow improve and turnover time substantially improves. This process adds cost but is profitable. Scalability and sustainability are under further study, as is the "halo effect" on the culture in other non-PIT Crew operating rooms., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To review the pharmacology, efficacy, and safety of the cyclin-dependent kinase (CDK) inhibitor, abemaciclib, in the treatment of advanced or metastatic breast cancer (MBC)., Data Sources: Relevant information was identified through a MEDLINE/PubMed (January 2000 to June 2018) literature search. The new drug application, prescribing information, and abstracts and posters from scientific meetings were also reviewed., Study Selection/data Extraction: The literature search was limited to human studies published in the English language. Phase 1, 2, and 3 studies evaluating the pharmacology, efficacy, or safety of abemaciclib for breast cancer were included., Data Synthesis: Abemaciclib is an oral, potent, small molecule inhibitor of CDK4 and CDK6 activity, which blocks retinoblastoma tumor suppressor protein phosphorylation and thereby prevents progression through the cell cycle. Three major clinical trials, MONARCH 1, 2, and 3, established the efficacy and safety of abemaciclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or MBC. In these trials, response rates were promising, ranging from 19.7% to 59%, and median progression-free survival was significantly prolonged over the control arm in 2 of the trials. Common adverse effects included diarrhea, neutropenia, nausea, abdominal pain, infections, and fatigue. Relevance to Patient Care and Clinical Practice: Although no head-to-head studies have been completed between the CDK4/6 inhibitors, abemaciclib may be an attractive option because of its continuous dosing and ability to be used as monotherapy., Conclusions: Abemaciclib is an effective and well-tolerated treatment for HR-positive, HER2-negative advanced or metastatic breast cancer.

In this paper we report about the setup we designed to isolate at about 1.5 kHz from mechanical noise an experimental payload of about 6.6 kg mass. We discuss the design guidelines and optimization by finite element analysis and we characterize the suspension performance by experimental measurements. While providing an attenuation of about 180 dB in all spatial directions at 1.5 kHz, our passive system is very compact and can be easily replicated whenever the need of a volume of few liters with very low vibration noise level in the 1-2 kHz range is needed.