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While interactions between neural crest and placode cells are critical for the proper formation of the trigeminal ganglion, the mechanisms underlying this process remain largely uncharacterized. Here, we show that the microRNA-(miR)203, whose epigenetic repression is required for neural crest migration, is reactivated in coalescing and condensing trigeminal ganglion cells. Overexpression of miR-203 induces ectopic coalescence of neural crest cells and increases ganglion size. Reciprocally, loss of miR-203 function in placode, but not neural crest, cells perturbs trigeminal ganglion condensation. Demonstrating intercellular communication, overexpression of miR-203 in the neural crestin vitroorin vivorepresses a miR-responsive sensor in placode cells. Moreover, neural crest-secreted extracellular vesicles (EVs), visualized using pHluorin-CD63 vector, become incorporated into the cytoplasm of placode cells. Finally, RT-PCR analysis shows that small EVs isolated from condensing trigeminal ganglia are selectively loaded with miR-203. Together, our findings reveal a critical role in vivo for neural crest-placode communication mediated by sEVs and their selective microRNA cargo for proper trigeminal ganglion formation.SIGNIFICANCE STRATEMENTCellular communication during early development plays a critical role. In this study, we demonstrate a unique role for a microRNA in cell-cell communication between the neural crest (NC) and placode cells (PC) during trigeminal ganglia (TG) formation. By utilizing loss and gain of function experiments in vivo, we demonstrate a requirement for miR-203 during cellular condensation to form the TG. We revealed that NC produces extracellular vesicles, selectively carrying miR-203, which is then taken up by the PC and regulates a sensor vector exclusively expressed in the placode. Taken together, our findings reveal a critical role in TG condensation for miR-203, produced by post-migratory NC and taken up by PC via extracellular vesicles.

In line with internationally defined goals of sustainable development, European agricultural policies today have a far-sighted vision for rural areas. Using a case study approach, this paper explores how receptive rural farms in Sicily are to a long-term vision of development. The study focuses on three key factors of a long-term vision, that is, digitalisation, innovation and sustainability, to examine not only whether farms have invested in these areas but also how they perceive their role in the post-pandemic era. Empirical results provide insights into the concentration of farms in the central inland areas of Sicily without any real long-term vision of development. Nevertheless, the analysis also shows that some of them do have a positive attitude to change.

Social media are an important growth opportunity for firms, especially small‐sized ones operating in peripheral and lagging regions. In this paper, we investigate not only whether firms are able to take this opportunity, but also if they are able to face the challenge of adopting social media at a professional level to obtain a significant economic impact, measured in terms of exporting activities. Exploring the Italian case, our empirical study indicates that smaller firms in lagging areas are more likely to adopt social media but at the same time less likely to use them at a professional level. This reflects poor strategic targets of social media adoption and lower probabilities of entering international markets. Los medios sociales son una oportunidad de crecimiento importante para las empresas, especialmente las de pequeno tamano que operan en regiones perifericas y atrasadas. En este articulo se investiga no solo si las empresas son capaces de aprovechar esta oportunidad, sino tambien si son capaces de afrontar el reto de adoptar los medios sociales a un nivel profesional para obtener un impacto economico significativo, medido en terminos de actividades de exportacion. Mediante el examen del caso de Italia, este estudio empirico senala que las empresas mas pequenas de las zonas atrasadas son mas propensas a adoptar los medios sociales, pero al mismo tiempo son menos propensas a utilizarlos a un nivel profesional. Esto refleja la escasez de objetivos estrategicos de la adopcion de los medios sociales y las menores probabilidades de entrar en los mercados internacionales. ソーシャルメディアは、企業にとって重要な成長の機会であるが、特に周辺地域や発展の遅れている地域で事業を行っている小規模企業にとって重要である。本稿では、企業がこの機会を利用できるかどうかだけでなく、重要な経済的影響を得るために専門的なレベルでソーシャルメディアを採用するという課題に企業が直面できるかどうかについても、輸出の業績で評価し、検討する。イタリアの事例を検証した今回の実証研究から、遅れている地域の小規模企業はソーシャルメディアを採用する確率が高いが、専門的なレベルでソーシャルメディアを利用する確率が低いことも示される。これは、ソーシャルメディアを採用するうえでの戦略目標が弱く、国際市場に参入できる可能性が低いことを反映している。

Spatial economic studies traditionally exploit areal data at the regional or sub-regional level. More recently, scholars have started to exploit spatial data of a different nature and, at the same time, extend the fields of application in economics. Specifically, this special issue contributes to the spatial economic literature by providing empirical evidence on a wide range of phenomena (socio-economic deprivation, land price volatility, electoral competition, real estate market, firm survival and tourism economics) and exploiting data at the municipality, firm, house and even individual level. At the same time, it tackles some of the methodological issues faced by the above-mentioned analyses.

Epithelial-to-mesenchymal transition (EMT) is a dramatic change in cellular physiology during development and metastasis, which requires coordination between cell signaling, adhesion, and membrane protrusions. These processes all involve dynamic changes in the plasma membrane; yet, how membrane lipid content regulates membrane function during EMT remains incompletely understood. By screening for differential expression of lipid-modifying genes over the course of EMT in the avian neural crest, we have identified the ceramide-producing enzyme neutral sphingomyelinase 2 (nSMase2) as a critical regulator of a developmental EMT. nSMase2 expression begins at the onset of EMT, and in vivo knockdown experiments demonstrate that nSMase2 is necessary for neural crest migration. We find that nSMase2 promotes Wnt and BMP signaling and is required to activate the mesenchymal gene expression program. Mechanistically, we show that nSMase2-dependent ceramide production is necessary for and sufficient to up-regulate endocytosis and is required for Wnt co-receptor internalization. Finally, inhibition of endocytosis in the neural crest mimics the loss of migration and Wnt signaling observed following nSMase2 knockdown. Our results support a model in which nSMase2 is expressed at the onset of neural crest EMT to produce ceramide and facilitate receptor-mediated endocytosis of Wnt and BMP signaling complexes, thereby activating promigratory gene expression. These results highlight the critical role of plasma membrane lipid metabolism in regulating transcriptional changes during developmental EMT programs.

The increasing share of renewable energy sources in energy systems will lead to unpredictable moments of surplus/deficit in energy production. To address this issue, users with heat pumps can provide support to power grid operators through flexible unit operation achieved via Demand Response programs. For buildings connected to low-temperature heating networks with ensured third-party access, further room for flexibility can be explored by investigating the production of surplus heat that can be sold to the network. A key aspect lies in the identification of the energy pricing options that could encourage such flexible operation of a heat pump by “thermal prosumers”. To this aim, the present study investigates the impact of ad hoc variations in the electricity purchasing price through discounts or penalties included in the “network cost” component of the price on cost-effective operation of a heat pump connected to the thermal network. To discuss the effects of different pricing options in terms of increased flexibility, an office building located in Italy and equipped with a high-temperature heat pump is adopted as the case study. A heuristic profit-oriented management strategy of the heat pump is assumed, and dynamic simulations are performed. The results indicate that at current electricity prices, the heat pump operation is profitable both when supplying the heat to meet the building’s requirements and when producing surplus heat for sale to the thermal network. In addition, it is revealed that the penalties applied to the electricity purchasing price are effective in encouraging changes in the heat pump operation strategy, reducing its average production (the building increasingly relying on buying heat from the network) and the associated electricity consumption by 46.0% and 79.7% in the “light” and “severe” local power deficit scenarios, respectively.

BACKGROUND: Ghrelin may influence several alcohol-related behaviors in animals and humans by modulating central and/or peripheral biological pathways. The aim of this exploratory analysis was to investigate associations between ghrelin administration and the human circulating metabolome during alcohol exposure in non-treatment seeking, heavy drinking individuals with alcohol use disorder (AUD). METHODS: We used serum samples from a randomized, crossover, double-blind, placebo-controlled human laboratory study with intravenous (IV) ghrelin or placebo infusion in two experiments. A loading dose (3 μg/kg) was followed by continuous infusion (16.9 ng/kg/min) of acyl-ghrelin or placebo during each session. The first experiment included an IV alcohol self-administration (IV-ASA) session, and the second experiment included an IV alcohol clamp (IV-AC) session, both under the counterbalanced infusion of ghrelin or placebo. Serum metabolite profiles were analyzed from repeated blood samples collected during each session. RESULTS: In both experiments, ghrelin infusion was associated with altered serum metabolite profile, specifically with significantly increased levels of cortisol (IV-ASA q-value = 0.0003, and IV-AC q < 0.0001), corticosterone (IV-ASA q = 0.0202, and IV-AC q

BMP signaling plays iterative roles during vertebrate neural crest development from induction through craniofacial morphogenesis. However, far less is known about the role of BMP activity in cranial neural crest epithelial-to-mesenchymal transition and delamination. By measuring canonical BMP signaling activity as a function of time from specification through early migration of avian midbrain neural crest cells, we found elevated BMP signaling during delamination stages. Moreover, inhibition of canonical BMP activity via a dominant negative mutant Type I BMP receptor showed that BMP signaling is required for neural crest migration from the midbrain, independent from an effect on EMT and delamination. Transcriptome profiling on control compared to BMP-inhibited cranial neural crest cells identified novel BMP targets during neural crest delamination and early migration including targets of the Notch pathway that are upregulated following BMP inhibition. These results suggest potential crosstalk between the BMP and Notch pathways in early migrating cranial neural crest and provide novel insight into mechanisms regulated by BMP signaling during early craniofacial development.

The paper proposes a new version of spatial shift-share decomposition to improve on the various approaches to conventional shift-share analysis found in the literature. The novelty of our proposal is that it enables researchers to assess spatial competitiveness effects controlling for the influence of industrial specialization at both regional and neighborhood level. This new version is applied to inbound tourism in Italian regions and enables us to identify the best and worst performers. Our empirical results identify favorable scenarios in some areas of the country, such as Sardinia as well as regional advantage in a sizeable number of well-known destinations.

Measurements of downwelling shortwave (SW) and longwave (LW) irradiance were carried out on an oceanographic buoy close to the island of Lampedusa (Italy), in the central Mediterranean Sea. Irradiance measurements on the buoy were acquired at high time resolution together with the radiometer pitch and roll angles. The measurements carried out during 2016 have been compared with ground-based observations made at the Lampedusa Atmospheric Observatory, about 15 km northeast of the buoy. The radiometers were compared before and after deployment on the buoy and are traceable to the World Radiometric Reference scale. The SW measurements were corrected for the thermal offset. A small bias (measurements over the sea are smaller than on land) of about −2 W m−2 is found in the daily mean SW, and a moderate bias of +6.2 W m−2 (irradiance over the sea is larger than on land) is found in the LW. Similar biases are found when instantaneous measurements obtained with horizontal radiometers, clean domes, and cloud-free conditions are selected, suggesting that impacts of the moving platform and poor dome cleaning are minor at this site. The effect of the mean tilt angle was also investigated. Deviations in the hourly mean SW irradiance are on the order of 20% for a mean offset of 4° with respect to the solar zenith angle; the effect of tilt angle on LW irradiance appears to be negligible. Radiative transfer calculations show that the observed biases may be ascribed to the differences in the instrument altitude (through radiation absorption, scattering, and emission by the atmospheric constituents in the lowest atmospheric layers) and in the SW surface albedo.

Summary Background and aims NUTrition Risk in the Critically ill (NUTRIC score) and modified Nutric score (mNUTRIC score) have been validated as screening tool for quantifying risk of adverse outcome in patients admitted in intensive care department. They differ for the measurement of IL-6 levels. In patients with COVID-19 disease the inflammatory response plays a crucial role leading to cytochine storm responsible of multiple organ damage. In this population, levels of IL-6 have been measured as indicator of inflammatory status. Aim of the study is to compare prognostic performance of both scores in predicting ICU mortality between patients with COVID-19 disease. Methods A single centre, retrospective, cohort study on patients admitted in ICU with confirmed diagnosis of COVID-19 was performed. Prognostic performance of NUTRIC score and mNUTRIC score were assessed and compared for discriminative abilities for ICU-mortality. Results 43 patients were enrolled, age 64 (55; 70), BMI 28 ± 4. Mean NUTRIC score was 2.5 ± 1, mNUTRIC was 2.6 ± 1.1. Mortality was 39.5%, all patients had low nutritional risk according to both scores (≤5 and ≤ 4 for NUTRIC and mNUTRIC score respectively). The discriminative ability of Nutric Score for ICU mortality was 0.675 (95% CI: 0.524–0.825), while that of mNutric score was 0.655 (0.513–0.861), p = 0.667. Conclusions Prognostic performance of Nutric score and mNutric score is comparable, but the discriminative ability is low even in patients with high inflammatory status as in COVID-19 affected population. These scores may not be appropriate in patients with COVID-19 for the determination of nutritional risk.

(1) Background: The aim of this review was to determine the state of clinical practice in the role of the combined approach of embolization and ablation in patients with secondary liver lesions greater than 3 cm who are not candidates for surgery, and to study its safety and efficacy. (2) Methods: Two reviewers conducted the literature search independently. Eight articles on the combined approach of embolization and ablation in secondary liver lesions were selected. (3) Results: The studies were published between 2009 and 2020. Two studies were prospective in design. The sample size was < 100 patients for all studies. All studies demonstrated the safety of the combined approach based on the low complication rate. Some studies lamented non-uniform systemic chemotherapy regimens and the variability in the sequence of embolization and ablation. (4) Conclusions: This review presents the combined approach of ablation and embolization in liver lesions greater than 3 cm as a safe therapeutic procedure with positive effects on patient survival. Prospective and multicentric studies are needed to further evaluate its efficacy.

With the advent of technologies such as ion array detectors and high energy permanent magnet materials, there is renewed interest in the unique focusing properties of the cycloidal mass analyzer and its ability to enable small, high-resolution, and high-sensitivity instruments. However, most literature dealing with the design of cycloidal mass analyzers assumes a single channel detector because at the time of those publications, compatible multichannel detectors were not available. This manuscript introduces and discusses considerations and a procedure for designing cycloidal mass analyzers coupled with focal plane ion array detectors. To arrive at a set of relevant design considerations, we first review the unique focusing properties of the cycloidal mass analyzer and then present calculations detailing how the dimensions and position of the focal plane array detector relative to the ion source determine the possible mass ranges and resolutions of a cycloidal mass analyzer. We present derivations and calculations used to determine the volume of homogeneous electric and magnetic fields needed to contain the ion trajectories and explore the relationship between electric and magnetic field homogeneity on resolving power using finite element analysis (FEA) simulations. A set of equations relating the electric field homogeneity to the geometry of the electric sector electrodes was developed by fitting homogeneity values from 78 different FEA models. Finally, a sequence of steps is suggested for designing a cycloidal mass analyzer employing an array detector.

We present the first results of the Fermilab Muon g-2 Experiment for the positive muon magnetic anomaly $a_\mu \equiv (g_\mu-2)/2$. The anomaly is determined from the precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency $\omega_a$ between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ${\tilde{\omega}'^{}_p}$ in a spherical water sample at 34.7$^{\circ}$C. The ratio $\omega_a / {\tilde{\omega}'^{}_p}$, together with known fundamental constants, determines $a_\mu({\rm FNAL}) = 116\,592\,040(54)\times 10^{-11}$ (0.46\,ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both $\mu^+$ and $\mu^-$, the new experimental average of $a_\mu({\rm Exp}) = 116\,592\,061(41)\times 10^{-11}$ (0.35\,ppm) increases the tension between experiment and theory to 4.2 standard deviations, Comment: 10 pages; 4 figures

Reversible heat pumps are increasingly adopted for meeting the demand for space heating and cooling in buildings. These technologies will play a key role not only in the decarbonization of space air conditioning but also in the development of 100% renewable energy systems. However, to assess the achievable benefits through the adoption of these technologies in novel applications, reliable models are needed, capable of simulating both their steady-state operation and dynamic response at different conditions in terms of heating loads, outdoor temperatures, and so on. The operation of heat pumps is often investigated by highly simplified models, using performance data drawn from catalogs and paying scarce attention to the critical influence of controllers. In this respect, this paper proposed an integrated thermodynamic and control modeling for a reversible air-to-water heat pump. The study considered a heat pump alternatively equipped with variable-speed compressors and constant-speed compressors with sequential control. The developed modeling was then used to investigate the operation of an air-to-water heat pump serving an office building in Italy. Results show that the model provided insights into the transient operation of variable-speed heat pumps (e.g., the settling time). Regarding constant-speed heat pumps, the model provided hints of interest to the control engineer to prevent, in the examined case study, the risk of quick compressors cycling on low-load heating days or when low-temperature heating devices are supplied. Finally, using a control strategy based on a heating curve for the variable-speed heat pump, results show the potential for a sensible increase in the average coefficient of performance, from 17% up to 50%.

Pancreatic surgery still remains burdened by high levels of morbidity and mortality with a relevant incidence of complications, even in high volume centers. This review highlights the interventional radiological management of complications after pancreatic surgery. The current literature regarding the percutaneous drainage of fluid collections due to pancreatic fistulas, percutaneous transhepatic biliary drainage due to biliary leaks and transcatheter embolization (or stent–graft) due to arterial bleeding is analyzed. Moreover, also, percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also examined. Moreover, a topic not usually treated in other similar reviewsas percutaneous intra-portal islet auto-transplantation for the prevention of pancreatogenic diabetes in case of extended pancreatic resection is also one of our areas of focus. In islet auto-transplantation, the patient is simultaneously donor and recipient. Differently from islet allo-transplantation, it does not require immunosuppression, has no risk of rejection and is usually efficient with a small number of transplanted islets.

Bronchial artery embolization (BAE) is considered the first choice treatment for hemoptysis. To our knowledge no cases of BAE using a recent ethylene vinyl alcohol copolymer agent (Squid) have been previously mentioned. Two cases of BAE for remitting hemoptysis using Squid and polyvinyl alcohol particles are reported in this technical note. The final angiographic control confirmed full exclusion of the target territory in both cases. Both patients felt some chest pain immediately after the embolization, not requiring any medications. No more episodes of hemoptysis occurred in the following 3 months after the procedure.

We present a retrospective analysis of a terrorist attack with incendiary grenades. We tried to analyse the correlation between carboxyhaemoglobin levels and distance of the corpse from the explosion site to check whether there is a direct relationship between them. In most fatal cases caused by grenade explosions reported in literature, death results from disruptive injuries or following multiorgan complications of the trauma, but here the terrorists used incendiary grenades causing serious burns to the victims with flames at the site of explosion. As a result, the external injuries were not fatal for most victims, especially those further from the explosion site where the flames and carbon monoxide from the fire played a significant role in causing death. The convergence of circumstantial data, autopsy results, and toxicological data led us to conclude that a direct link between the carboxyhaemoglobin level and distance from the site of explosion could not be made. Understanding the limitation of the value of linking such data is important both for police and forensic pathologists as this can reduce potential errors in reconstructing the dynamics of the event.

The use of a pocked-sized, wireless-Bluetooth ultrasound portable system with display images presented on a tablet facilitated the work of our radiologists during the first wave of coronavirus disease 2019 (COVID-19) to perform diagnostic and interventional procedures in bedridden patients. The device is equipped with a battery-powered probe without cables that transmits images to a tablet (or a cell phone) through a dedicated App. We hypothesise in future to extend diagnostic and low-complexity interventional procedures from hospitalised patients to at-home patients who are not able to mobilise out of bed or are difficult to transport. This domiciliary service might also reduce the overhead of hospital accesses.

The mass of the

Depressive disorders are among the most burdensome diseases globally in terms of prevalence, as well as in terms of quality of life, morbidity, and mortality. Hence, it is becoming increasingly common for primary care physicians to administer and monitor the treatment of individuals affected by depressive disorders. In this framework, Therapeutic Drug Monitoring (TDM) comes to the forefront. TDM is the measurement of specific drugs in the blood or plasma/serum, and its usefulness lies in the fact that it allows physicians to assess drug levels to personalize and optimize treatments. TDM has been used for decades to measure several classes of psychotropic drugs, such as antiepileptics and antipsychotics, but the use of this tool is still in its infancy in regard to antidepressants. In the context of primary care, TDM of antidepressant drug treatment shows promise, as it can enable primary care physicians to monitor the safety and efficacy of the treatment, leaving to secondary care, i.e., psychiatrists, the management of the more complex clinical cases.

Among mercury-related intoxications, the re-emerging of mercuric chloride poisoning has been recently described in literature. Only sparse data, reporting the clinical symptoms, the anatomo-pathological findings, the analytical procedures or the treatment have been published and no exhaustive analysis of all these factors exists in literature. The classic symptoms associated with toxicity of mercuric chloride is a combination of renal, gastrointestinal (GI) and central nervous system (CNS) damages, eventually leading to death. Fatalities related to exposure to mercuric chloride have been reported since the nineteenth century. To date, there have been 45 published cases in the medical literature in which the intoxication or the death is attributed to mercuric chloride. In this review, we will describe the modern medical treatments, with particular attenztion to the developments of the lasts two decades, in order to provide an exhaustive description of the clinical symptoms, the post-mortem findings, and the analytical procedures to act out when mercuric chloride intoxication occurs. The analysis of the data obtained permitted us to accurately describe all the organs and apparatus involved in mercuric chloride intoxication. The target organs were the kidneys, the GI tract and the CNS. A description of the analytical procedures for the determination of mercuric chloride in biological materials, to carry out in vivo and in post-mortem samples has also been described.

Air conditioning accounts for a large share of energy usage in residential and tertiary sectors. Renewable energy technologies offer promising solutions to reduce the environmental impacts of meeting buildings’ energy loads. The possibility of using the soil as a thermal reservoir for heating and cooling systems has gained growing attention in the last decade due to its high potential for energy saving. In this paper, the benefits achievable using ground source chillers for air conditioning in an office building located in Southern Italy are discussed. A multiple chillers system coupled with a borehole heat exchanger is investigated and compared to conventional air-cooled and water-cooled systems. The analysis relies on detailed modeling of the main plant components and exploits a novel approach to calculating the thermal resistance of the borehole. Results show that the ground coupled multiple chillers system achieves a 6.516 average energy efficiency ratio, which is 53.2% higher than the reference air-cooled system and 6.5% higher than the conventional water-cooled system. In addition, a hybrid scheme that integrates the borehole heat exchanger with a cooling tower achieves a 19.5% reduction in make-up water consumption. A sensitivity analysis demonstrates that increasing the borehole depth could lead to a significant variation in the system performance, with different trends for simple and hybrid configurations. The proposed study puts forth a reference for the design and operation of this technology for covering the space-cooling demand of buildings in Mediterranean climates.

Epithelial-to-mesenchymal transition (EMT) is a dynamic process that produces migratory cells from epithelial precursors. However, EMT is not binary; rather it results in migratory cells which adopt diverse strategies including collective and individual cell migration to arrive at target destinations. Of the many embryonic cells that undergo EMT, the vertebrate neural crest is a particularly good example which has provided valuable insight into these processes. Neural crest cells from different species often adopt different migratory strategies with collective migration predominating in anamniotes, whereas individual cell migration is more prevalent in amniotes. Here, we will provide a perspective on recent work toward understanding the process of neural crest EMT focusing on how these cells undergo collective and individual cell migration.

We develop a model in which collateral serves to protect creditors from the claims of other creditors. We find that, paradoxically, borrowers rely most on collateral when pledgeability is high. This is when taking on new debt is easy, which dilutes existing creditors. Creditors thus require collateral for protection against possible dilution by collateralized debt. There is a collateral rat race. But collateralized borrowing has a cost: it encumbers assets, constraining future borrowing and investment. There is a collateral overhang. Our results suggest that policies aimed at increasing the supply of collateral can backfire, triggering an inefficient collateral rat race. Likewise, upholding the absolute priority of secured debt can exacerbate the rat race.

Objective Therapeutic drug monitoring helps clinicians in choosing the right drug and adjust its dose in specific patients. To this end, we aimed to assess time patterns of risperidone and its metabolite, 9-hydroxyrisperidone, in children and adolescents with oppositional defiant and/or conduct disorder. Methods We measured plasma concentrations of risperidone and 9-hydroxyrisperidone, their sum (active moiety, AM) and ratio, as well as plasma concentrations corrected for daily dose (C/D), from 140 children/adolescents with the above-mentioned disorders. We used Student's t test to compare females versus males, patients under versus over 16-year-old, patients with lower versus higher than the median body weight, and patients with lower versus higher than the median body mass index (BMI). Two mixed-effects logistic regression models were fitted for risperidone/9- hydroxyrisperidone ratio and AM, respectively, by considering risperidone daily dose and patients' demographic characteristics. Results Females had higher 9-hydroxyrisperidone and AM plasma concentrations than males (p = 0.004 and p = 0.034). Younger patients had lower risperidone plasma concentration and risperidone/9-hydroxyrisperidone ratio (p = 0.02 and p = 0.021), but higher C/D 9-hydroxyrisperidone and AM than older patients (p = 0.013 and p = 0.043). Lower-weight patients had lower plasma risperidone and risperidone/9-hydroxyrisperidone ratio (p = 0.014 and p = 0.019), but higher C/D 9-hydroxyrisperidone concentration than heavier patients (p = 0.03). All these results could be accounted for by daily dose. Patients with lower and higher BMI did not differ significantly. Regression analyses showed that only risperidone daily dose predicted risperidone/9-hydroxyrisperidone ratio, whereas risperidone daily dose, sex, and age predicted AM. Conclusion Clinicians prescribing risperidone need to consider sex, age, and weight, but not BMI when adjusting daily doses.

We develop a dynamic model of board decision-making akin to dynamic voting models in the political economy literature. We show a board could retain a policy all directors agree is worse than an available alternative. Thus, directors may retain a CEO they agree is bad—deadlocked boards lead to entrenched CEOs. We explore how to compose boards and appoint directors to mitigate deadlock. We find board diversity and long director tenure can exacerbate deadlock. We rationalize why CEOs and incumbent directors have power to appoint new directors: to avoid deadlock. Our model speaks to short-termism, staggered boards, and proxy access.

Deep brain stimulation has become an established therapeutic choice to manage the symptoms of medically refractory Parkinson's disease. Its efficacy is highly dependent on the accuracy of electrodes' positioning in the correct anatomical target. During DBS procedure, the opening of the dura mater induces the displacement of neural structures. This effect mainly depends on the loss of the physiological negative intracranial pressure, air inflow, and loss of cerebrospinal fluid. Several studies concentrated on correcting surgical techniques for DBS electrodes' positioning in order to reduce pneumocephalus which may result in therapeutic failure. The authors focused in particular on reducing the brain air window and maintaining the pressure gradient between intra- and extracranial compartments. A significant reduction of pneumocephalus and brain shift was obtained by excluding the opening of the subarachnoid space, by covering the dura mater opening with tissue sealant and by reducing the intracranial pressure in general anesthesia. Smaller burr hole diameters were not statistically relevant for reducing air inflow and displacement of anatomical targets. The review of the literature showed that conserving a physiological intra-extracranial pressure gradient plays a fundamental role in avoiding pneumocephalus and consequent displacement of brain structures, which improves surgical accuracy and DBS long-term results.

Low voltage activated (ICa-LVA) calcium currents including Cav1.3 and T-type calcium current (ICa-T) have not been reported in adult human left ventricular myocytes (HLVMs). We tried to examine the...

The detection of peritoneal carcinomatosis in patients with ovarian cancer is crucial to establish the correct therapeutic planning (debulking surgery versus neoadjuvant chemotherapy).Often, however, the nodules of peritoneal carcinomatosis are very small in size or have a reticular appearance that can mimic the fat stranding that is typical of acute inflammation conditions. Our hypothesis is that the use of dual-layer spectral computed tomography with its applications, such as virtual monoenergetic imaging and Z-effective imaging, might improve the detection and the characterisation of peritoneal nodules, increasing sensitivity and diagnostic accuracy, as recently described for other oncological diseases.

This chapter presents some potential applications of salinity gradient power-heat engines (SGP-HEs) in power generation systems and industrial processes, where low-temperature waste heat flows could be available. In order to show this concept, five case studies are proposed. In the first case study, a thermoelectric power plant is considered. The analysis evaluates the possibility to convert the low-grade heat content of flue gases into additional electricity via SGP-HEs. In the second case study, an SGP-HE is coupled with an organic Rankine cycle (ORC) plant to enhance the amount of electricity produced from a medium-temperature waste heat flow released by an industrial process. In the third case study, a gas turbine-based cogeneration plant serving an industrial process is assumed. The analysis assesses whether the inclusion of an SGP-HE as a part of the cogeneration system contribute to improve the energy performance of the plant and increase the economic revenues arising from financial support mechanisms provided by laws. In the fourth case study, the convenience to use an SGP-HE along with heat pumps for upgrading low-temperature waste heat is investigated. In the fifth and last case study, an SGP-HE fueled by industrial waste heat was used to drive a reverse osmosis (RO) plant for producing desalted water. For each case study, energy savings, economic profits, and reduction in carbon dioxide emissions are shown and discussed.

High-energy physics is primarily concerned with uncovering the laws and principles that govern nature at the fundamental level. Research in this field usually relies on probing the boundaries of established physics, an undertaking typically associated with extreme energy and distance scales. It is therefore unsurprising that particle physics has traditionally been dominated by large-scale experimental methods often involving high energies, such as colliders and storage rings, cosmological and astrophysical observations, large-volume detector systems, etc. However, high-sensitivity measurements in smaller experiments, often performed at lower energies, are presently experiencing a surge in importance for particle physics for at least two reasons. First, they exploit synergies to adjacent areas of physics with recent advances in experimental techniques and technology. Together with intensified phenomenological explorations, these advances have led to the realization that challenges associated with weak couplings or the expected suppression factors for new physics can be overcome with such methods while maintaining a large degree of experimental control. Second, many of these measurements broaden the range of particle-physics phenomena and observables relative to the above set of more conventional methodologies. Combining such measurements with the conventional efforts above therefore casts both a wider and tighter net for possible effects originating from physics beyond the Standard Model (BSM). This paper argues that this assessment points at a growing impact of such methods and measurements on high-energy physics, and therefore warrants direct support as particle-physics research. Leveraging the recent rapid progress and bright outlook associated with such studies for high-energy physics, could yield high returns, but requires substantial and sustained efforts by funding agencies., Comment: Contribution to Snowmass 2021, 55 pages, 5 figures

We examine how the saccade mechanism from biological vision can be used to make deep neural networks more efficient for classification and object detection problems. Our proposed approach is based on the ideas of attention-driven visual processing and saccades, miniature eye movements influenced by attention. We conduct experiments by analyzing: i) the robustness of different deep neural network (DNN) feature extractors to partially-sensed images for image classification and object detection, and ii) the utility of saccades in masking image patches for image classification and object tracking. Experiments with convolutional nets (ResNet-18) and transformer-based models (ViT, DETR, TransTrack) are conducted on several datasets (CIFAR-10, DAVSOD, MSCOCO, and MOT17). Our experiments show intelligent data reduction via learning to mimic human saccades when used in conjunction with state-of-the-art DNNs for classification, detection, and tracking tasks. We observed minimal drop in performance for the classification and detection tasks while only using about 30\% of the original sensor data. We discuss how the saccade mechanism can inform hardware design via ``in-pixel'' processing., Comment: 4 Pages, 6 figures, will be presented at CVPR2022-NeuroVision workshop as a Lightning talk

This work presents the ASIMOV Prize for scientific publishing, which was launched in Italy in 2016. The prize aims to bring the young generations closer to scientific culture, through the critical reading of popular science books. The books are selected by a committee that includes scientists, professors, Ph.D. and Ph.D. students, writers, journalists and friends of culture, and most importantly, over 800 school teachers. Students are actively involved in the prize, according to the best practices of public engagement: they read, review the books and vote for them, choosing the winner. The experience is quite successful: 12,000 students from 270 schools all over Italy participated in the last edition. The possibility of replicating this experience in other countries is indicated, as was done in Brazil in 2020 with more than encouraging results., Comment: Presented at ICHEP 2022 (Bologna, 6-13 July 2022)

We present a scalable in-pixel processing architecture that can reduce the data throughput by 10X and consume less than 30 mW per megapixel at the imager frontend. Unlike the state-of-the-art (SOA) analog process-in-pixel (PIP) that modulates the exposure time of photosensors when performing matrix-vector multiplications, we use switched capacitors and pulse width modulation (PWM). This non-destructive approach decouples the sensor exposure and computing, providing processing parallelism and high data fidelity. Our design minimizes the computational complexity and chip density by leveraging the patch-based feature extraction that can perform as well as the CNN. We further reduce data using partial observation of the attended objects, which performs closely to the full frame observations. We have been studying the reduction of output features as a function of accuracy, chip density and power consumption from a transformer-based backend model for object classification and detection., Comment: 5 pages, 4 figures