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Repeat expansion disorders (REDs) are a devastating group of predominantly neurological diseases. Together they are common, affecting 1 in 3,000 people worldwide with population-specific differences. However, prevalence estimates of REDs are hampered by heterogeneous clinical presentation, variable geographic distributions and technological limitations leading to underascertainment. Here, leveraging whole-genome sequencing data from 82,176 individuals from different populations, we found an overall disease allele frequency of REDs of 1 in 283 individuals. Modeling disease prevalence using genetic data, age at onset and survival, we show that the expected number of people with REDs would be two to three times higher than currently reported figures, indicating underdiagnosis and/or incomplete penetrance. While some REDs are population specific, for example, Huntington disease-like 2 in Africans, most REDs are represented in all broad genetic ancestries (that is, Europeans, Africans, Americans, East Asians and South Asians), challenging the notion that some REDs are found only in specific populations. These results have worldwide implications for local and global health communities in the diagnosis and counseling of REDs.

We retrospectively analyzed real-world data from the ARON-1 project for patients with papillary renal cell carcinoma who received first-line immune-based combinations or tyrosine kinase inhibitors. Immune-based combinations were associated with better 1-yr and 2-yr overall survival rates, better median progression-free survival, and a better objective response rate. Immune-based combinations are the preferable option for first-line treatment in this setting.

A definitive diagnosis of gastroesophageal reflux disease (GERD) depends on endoscopic and/or pH‐study criteria. However, high resolution manometry (HRM) can identify factors predicting GERD, such as ineffective esophageal motility (IEM), esophago‐gastric junction contractile integral (EGJ‐CI), evaluating esophagogastric junction (EGJ) type and straight leg raise (SLR) maneuver response. We aimed to build and externally validate a manometric score (Milan Score) to stratify the risk and severity of the disease in patients undergoing HRM for suspected GERD. A population of 295 consecutive patients undergoing HRM and pH‐study for persistent typical or atypical GERD symptoms was prospectively enrolled to build a model and a nomogram that provides a risk score for AET > 6%. Collected HRM data included IEM, EGJ‐CI, EGJ type and SLR. A supplemental cohort of patients undergoing HRM and pH‐study was also prospectively enrolled in 13 high‐volume esophageal function laboratories across the world in order to validate the model. Discrimination and calibration were used to assess model's accuracy. Gastroesophageal reflux disease was defined as acid exposure time >6%. Out of the analyzed variables, SLR response and EGJ subtype 3 had the highest impact on the score (odd ratio 18.20 and 3.87, respectively). The external validation cohort consisted of 233 patients. In the validation model, the corrected Harrel c‐index was 0.90. The model‐fitting optimism adjusted calibration slope was 0.93 and the integrated calibration index was 0.07, indicating good calibration. A novel HRM score for GERD diagnosis has been created and validated. The MS might be a useful screening tool to stratify the risk and the severity of GERD, allowing a more comprehensive pathophysiologic assessment of the anti‐reflux barrier. ClinicalTrials.gov(Identifier: NCT05851482).

The psychedelic prodrug psilocybin has shown therapeutic benefits for the treatment of numerous psychiatric conditions. Despite positive clinical end points targeting depression and anxiety, concerns regarding the duration of the psychedelic experience produced by psilocybin, associated with enduring systemic exposure to the active metabolite psilocin, pose a barrier to its therapeutic application. Our objective was to create a novel prodrug of psilocin with similar therapeutic benefits but a reduced duration of psychedelic effects compared with psilocybin. Here, we report the synthesis and functional screening of 28 new chemical entities. Our strategy was to introduce a diversity of cleavable groups at the 4-hydroxy position of the core indole moiety to modulate metabolic processing. We identified several novel prodrugs of psilocin with altered pharmacokinetic profiles and reduced pharmacological exposure compared with psilocybin. These candidate prodrugs have the potential to maintain the long-term benefits of psilocybin therapy while attenuating the duration of psychedelic effects.

In response to the dynamic and ever-changing landscape of supply chains, which are continually challenged by internal and external factors, there is a critical need for continuous adaptation, learning, and improvement. Historically, scholars have argued that traditional information systems lack the capacity to effectively support resilience strategies within supply chains. However, advancements in Industry 4.0 technologies may have shifted this paradigm. This article explores how enabling technologies (ET) can support the development of resilient operations at the supply chain level. To that end, a systematic literature review is combined with a multiple case study to understand how these technologies can support the development of elements of resilience. Three distinct sectors from different geographical locations were chosen for this study: an agri-food company in Brazil, a manufacturing firm in the food industry in Canada, and a logistics service provider in Italy. Integrating both theoretical insights and empirical findings leads to the formulation of a research framework, the primary contribution of this study, which serves as a resource for scholars and practitioners aiming to leverage ET to increase supply chain resilience. The article concludes with key findings and suggests avenues for future research.

Industry 5.0 addresses the human challenges of Industry 4.0 as a human-centric solution, placing the worker’s well-being at the centre of the production process. If, on the one hand, the last technologies support operator 5.0 to embrace the collaborative potential of human-machine cooperation, on the other hand, the complexity, as well as the rapid evolution of new technologies, could have the potential to produce immediate stress reaction leading to reduce the workers’ well-being. Recent studies have proved that the maintenance area is experiencing many innovations in terms of approaches and technologies. In this field, the rapid progress of technological equipment is leading to an increase in the human operators’ mental workload. This paper presents preliminary concepts and objectives of a Decision Support System (DSS) for the Diagnosis and Evaluation of Maintenance Operations. The DSS intends to assist industrial professionals and stakeholders in maintenance tasks characterised by significant cognitive demands. Considering variables such as task complexity and the mental and physical condition of operators involved in a maintenance task, the DSS will provide real-time recommendations for selecting the most suitable operators by promoting a gradual technology introduction, increasing industrial performance, and ensuring the well-being of the workers.

The aim of this study was to evaluate occurrences and patterns of multimorbidity in adults from a southern Brazilian city. A population-based cross-sectional study was carried out in 2012 through face-to-face interviews with adults (20 or more years) living in Pelotas, southern Brazil. Multimorbidity was evaluated by a list of 11 morbidities (based on medical diagnosis; Patient Health Questionnaire 9 for depression; and Anatomical Therapeutic Chemical index) and operationalized according to two cutoff points: ≥2 and ≥3 morbidities. Descriptive analysis and factor analysis (FA) were performed. The sample was made up of 2927 adults. Multimorbidity reached 29.1 % (95 % CI: 27.1; 31.1) for ≥2, and 14.3 % (95 % CI: 12.8; 15.8) for ≥3 morbidities and was greater in females, older people, those with less schooling and those from lower economic classes. Four pairs (frequency ≥5 %) and four triplets (frequency ≥2 %) were observed. Two patterns of morbidities (cardiometabolic and joint problems; and respiratory diseases) explained 93 % of total variance. Multimorbidity was common in the studied population. The observed patterns may be used to generate and improve Brazilian diseases guidelines.

The Industry 4.0 (I4.0) revolution has led to new concepts and transformations toward technological innovations. In the manufacturing sector, the use of collaborative robots (cobots) has significantly increased in the last few years, enabling them to work safely alongside humans in a shared workspace. Within this perspective, small- and medium-sized enterprises (SMEs) have been facing several challenges compared to large organisations regarding the adoption of cobots. Based on the literature, this paper aims to introduce a techno-economic feasibility model to evaluate the viability of using cobots in a shared workplace, with a focus on SMEs. Consistent with the papers aim, a conceptual model was developed, supported by experts opinions using the Delphi method. The results of this work incorporate contributions to both the academic and industrial communities.

The exponential increase in the availability of large-scale mobility data has fueled the vision of smart cities that will transform our lives. The truth is that we have just scratched the surface of the research challenges that should be tackled in order to make this vision a reality. Consequently, there is an increasing interest among different research communities (ranging from civil engineering to computer science) and industrial stakeholders in building knowledge discovery pipelines over such data sources. At the same time, this widespread data availability also raises privacy issues that must be considered by both industrial and academic stakeholders. In this paper, we provide a wide perspective on the role that big data have in reshaping cities. The paper covers the main aspects of urban data analytics, focusing on privacy issues, algorithms, applications and services, and georeferenced data from social media. In discussing these aspects, we leverage, as concrete examples and case studies of urban data science tools, the results obtained in the “City of Citizens” thematic area of the Horizon 2020 SoBigData initiative, which includes a virtual research environment with mobility datasets and urban analytics methods developed by several institutions around Europe. We conclude the paper outlining the main research challenges that urban data science has yet to address in order to help make the smart city vision a reality.

We study the near-infrared (NIR) radiation-induced attenuation (RIA) of a single-mode (SM) optical fiber composed by a Ge-doped core, a ~4- $\mu $ m-thick P-doped inner cladding and pure Silica outer cladding. Its potential for dosimetry application has been investigated by spectral RIA measurements. The RIA, measured at 1550 nm, exhibits a linear growth as a function of the accumulated dose up to ~1 kGy(SiO2). The sensitivity to radiation, expressed by the coefficient $\xi $ , results in 164 mdB km−1 Gy−1 in the 0–1 kGy dose range, ~24 times lower than the one of an SM P-doped optical fiber. Furthermore, $\xi $ almost does not depend on the dose-rate, its variation remains on the order of 6% (10 mdB km−1 Gy−1) for the dose-rate range from 10 mGy s−1 up to 10 Gy s−1. At wavelengths lower than ~1450 nm, our measurements reveal a stronger dose rate dependence and less interesting dosimetric properties. Finally, a preliminary test on the 1550 and 1625 nm RIA at different irradiation temperatures (from room temperature to 90 °C) showed no significant changes in the $\xi $ radiation sensitivity coefficients.

The Brazilian National Network of Alternative Methods (RENAMA), which is linked to the Ministry of Science, Technology and Innovation, is currently comprised of 51 laboratories from CROs, academia, industry and government. RENAMA’s aim is to develop and validate new approach methodologies (NAMs), as well as train researchers and disseminate information on their use — thus reducing Brazilian, and consequently Latin American, dependence on external technology. Moreover, it promotes the adoption of NAMs by educators and trained researchers, as well as the implementation of good laboratory practice (GLP) and the use of certified products. The RENAMA network started its activities in 2012, and was originally comprised of three central laboratories — the National Institute of Metrology, Quality and Technology (INMETRO); the National Institute of Quality Control in Health (INCQS); and the National Brazilian Biosciences Laboratory (LNBio) — and ten associated laboratories. In 2022, RENAMA celebrated its 10th anniversary, a milestone commemorated by the organisation of a meeting attended by different stakeholders, including the RENAMA-associated laboratories, academia, non-governmental organisations and industry. Ninety-six participants attended the meeting, held on 26 May 2022 in Balneário Camboriú, SC, Brazil, as part of the programme of the XXIII Brazilian Congress of Toxicology 2022. Significant moments of the RENAMA were remembered, and new goals and discussion themes were established. The lectures highlighted recent innovations in the toxicological sciences that have translated into the assessment of consumer product safety through the use of human-relevant NAMs instead of the use of existing animal-based approaches. The challenges and opportunities in accepting such practices for regulatory purposes were also presented and discussed.

The purpose of this paper is to present and assess the literature about the determinants of public spending. Its originality is the adoption of a methodological perspective. Does econometrics allow economists to discover universal constants for public spending or is it only another way of writing the history of public finance? The economic theory of the size of government includes 23 explanations and 78 explanatory variables. The size of government reflects the preferences of citizens (demand model), the power of politicians and bureaucrats to impose their interests against citizens' interests (supply model) and the constitutional design that governments face in raising revenue. Nonetheless, the great instability of econometric tests shows, all the difficulties of the science of public finance in finding a constant and discovering real causality between these variables. The analytical consequence of this result is the great futility of the search for a general law of the dynamic of public spending. This futility can be interpreted as a consequence of the complexity of political exchange. The size of the state is a multi-causal phenomenon. The prescriptive consequence is that it is not possible to use quantitative analysis to defend a form of 'causal manipulationism' and predict the timing of state reforms and a political strategy to reduce the share of public spending in production. Econometrics is only one way of reporting the history of public finances. Keywords Causality * Qualitative history * Public spending and econometrics JEL E62, Introduction The overall growth of government spending over the last 150 years in industrial societies is an established fact. Government expenditures in 2015 represented 40.9% of gross domestic product (GDP) [...]

ABSTRACT Lateral vehicle impact tests on moulded wooden tubes were performed to estimate the suitability for infrastructure equipment like lighting poles. Initial speeds of the impacting vehicle of 35, 50 [...]

ABSTRACT The purpose of this paper is to study the dynamic and static three-dimensional behavior of a dryassembled masonry cross vault, through the comparison of Distinct Element Modeling results and [...]

Pore water pressure is the main driving force for soil collapse in nature. River dikes, earth dams, and the foundation of structures built in water are eroded by internal infiltration into the soil (seepage/piping) or flow (scouring/overtopping). Climate change and the spread of urbanization increase the fragility of areas prone to flooding. Current methodologies for early detection of ongoing damage caused by water to these structures are inadequate for preventing structural collapse. Traditional hydrogeological monitoring is based on visual inspection of the infrastructure. In this research, a novel distributed fiber-optic pressure sensor (DPS) was developed to measure variations in the pore water pressure with a spatial resolution of decimeters and over lengths in the order of kilometers. Extensive controlled pressure and temperature variation tests were carried out for calibrating the water pressure and temperature sensitivity of the DPS. The resulting design of the sensor achieved a high sensitivity of 0.1 kPa (1 cmH2O). Additionally, the DPS functionality was validated in a reduced-scale test embankment.

El síndrome de Poland es una malformación infrecuente (un caso por cada 30.000 nacimientos) que combina, en diversos grados, anomalías del tórax y del miembro superior homolateral. La anomalía constante es la agenesia de los fascículos esternocostales y esternoclaviculares del pectoral mayor. Con frecuencia hay asimetría mamaria, con hipoplasia de una mama y del complejo areolomamilar homolateral. Las malformaciones de la mano, presentes en alrededor del 20% de los casos, son numerosas y varían en gravedad, pero la más frecuente es la braquimesofalangia. Este cuadro clínico es más frecuente en los varones (proporción por sexos de 3/2) y más a menudo en el hemitórax derecho. La etiopatogenia está a favor de una anomalía vascular subclavia embrionaria (6.ª semana). Nunca hay consecuencias funcionales en caso de afectación torácica, incluso de la mano, sólo molestias estéticas. Una clasificación reciente, basada en la experiencia de 151 pacientes intervenidos, permite orientar las opciones terapéuticas. En los últimos años, la cirugía reconstructiva se ha beneficiado de la tecnología digital, con implantes torácicos de elastómero de silicona hechos a medida mediante diseño y fabricación asistidos por ordenador, a partir de una tomografía computarizada. También pueden utilizarse como complemento otras técnicas que combinan implantes mamarios e injertos de grasa, según los casos. El colgajo clásico del músculo dorsal ancho rara vez se utiliza. En función de la edad, el sexo y la gravedad de las anomalías toracomamarias, puede proponerse una estrategia terapéutica adaptada a cada caso de síndrome de Poland.

Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation.

Systematic screening of morphine pathway intermediates in engineered yeast revealed key biosynthetic enzymes displaying potent feedback inhibition: 3′-hydroxy-N-methylcoclaurine 4′-methyltransferase (4′OMT), which yields (S)-reticuline, and the coupled salutaridinol-7-O-acetyltransferase (SalAT) and thebaine synthase (THS2) enzyme system that produces thebaine. The addition of deuterated reticuline-d1 to a yeast strain able to convert (S)-norcoclaurine to (S)-reticuline showed reduced product accumulation in response to the feeding of all four successive pathway intermediates. Similarly, the addition of deuterated thebaine-d3 to a yeast strain able to convert salutaridine to thebaine showed reduced product accumulation from exogenous salutaridine or salutaridinol. In vitro analysis showed that reticuline is a noncompetitive inhibitor of 4′OMT, whereas thebaine exerts mixed inhibition on SalAT/THS2. In a yeast strain capable of de novo morphine biosynthesis, the addition of reticuline and thebaine resulted in the accumulation of several pathway intermediates. In contrast, morphine had no effect, suggesting that circumventing the interaction of reticuline and thebaine with 4′OMT and SalAT/THS2, respectively, could substantially increase opiate alkaloid titers in engineered yeast.

The capabilities of additive manufacturing processes have been increased in the last years, and this trend is not close to an end. Researchers, in gas turbine industry, are focusing on the technology implementation on cooling systems. The aim of the present work is to investigate the performances of eight different geometries in order to exploit the cooling potential of some challenging latticework schemes with respect to traditional ones. Test coupons consisting of some cooling structures embedded inside a rectangular cooling channel were fabricated by means of Direct Metal Laser Melting (DMLM) technique. Since an aim of the present work is to evaluate the shape deformation associated with this additive process, the results of CT scan imaging technique are presented. The performances are characterized both in terms of averaged heat transfer and friction factor values inside the test coupons by means of steady-state technique with a constant wall temperature boundary condition. The investigated flow Reynolds numbers range from 18000 to 40000. These values allow the authors to provide a deeper understanding of the latticework structures performances at Reynolds numbers beyond the range typically investigated in the literature. Although the obtained results reveal that none of the tested geometries outperforms the other ones, the latticework arrangements show a heat transfer enhancement with respect to a porosity decrease. In addition, the good capability in terms of heat transfer of the lattice structures suggests the use of such technologies for twofold optimization process based on mechanical resistance and heat transfer characteristics.

Two particles are identical if all their intrinsic properties, such as spin and charge, are the same, meaning that no quantum experiment can distinguish them. In addition to the well known principles of quantum mechanics, understanding systems of identical particles requires a new postulate, the so called symmetrisation postulate. In this work, we show that the postulate corresponds to exchangeability assessments for sets of observables (gambles) in a quantum experiment, when quantum mechanics is seen as a normative and algorithmic theory guiding an agent to assess her subjective beliefs represented as (coherent) sets of gambles. Finally, we show how sets of exchangeable observables (gambles) may be updated after a measurement and discuss the issue of defining entanglement for indistinguishable particle systems. [ABSTRACT FROM AUTHOR]

Hexavalent chrome plating has been used for decades in such applications as aircraft landing gear, hydraulic actuators, gas turbine engines, helicopter dynamic components and propeller hubs, but there have been [...]

Lambl excrescence describing rare cardiac growths that develop at the valvular coaptation sites of the heart which are seen as a thin, hypermobile and filiform strand on an echocardiogram. These filiform strands can be noted in association with embolic stroke. Also heart failure (HF) and stroke frequently coexist because of an overlap of shared risk factors and subsequent mechanisms and a higher risk of stroke is present also in HF patients in sinus rythm (SR). The clinical case concerns a 54–year–old woman. In March 2020 she was admitted for ischemic stroke by occlusion of middle cerebral artery subjected to thrombolysis and mechanical thromboctomy. Electrocardiogram showed SR and left branch block. Echocardiogram and echocardiogram transesophageal showed left ventricular (LV) dysfunction (EF 40%) withouth clear presence of emboligen sources. Thrombophilic screening and neurological checks were negative. Single antiaggregant therapy has been started. New hospitalization in October 2023 for recurrent ischemic stroke. Echocardiogram showed worsening of LV dysfunction (EF 20%). Transesophageal echocardiogram showed the presence of a filiform filament on the mitral leaflets on the atrial side (Fig 1) without the presence of intracavitary thrombi. Coronary TC angiography (Fig 2) was negative. Cardiac magnetic resonance (Fig 3) confirmed reduced ejection fraction and showed subepicardial late gadolinium enhancement in lateral wall. There are no clear evidence–based guidelines for the treatment of Lambl excrescences. When associated with stroke, an exhaustive stroke workup to identify the potential cause of stroke should always be undertaken. If the workup remains negative without any identifiable cause, then the patients can be treated with antiplatelet agents such as aspirin and clopidogrel or anticoagulation with warfarin. Also the indication to antithrombotic strategies in patients with HF, SR and stroke is controversial. There are no data to support a routine strategy of anticoagulation in patients with HF with LV dysfuncion in SR who do not have history of paroxysmal atrial fibrillation (ESC 2022 HF guidelines). So which therapy to start in young patient, with recurrent strokes, heart failure /severe LV dysfunction and mitral lambl excrescence? Oral anticoagulant? Double platelet antiaggregation? Oral anticoagulant and single platelet antiaggregation? Definitely the choice is not simple but we decided to start warfarin and continue follow–up.

Papillary fibroelastomas are small and pedunculated left side valves associated mass, that frequently causing cerebral embolization; they are composed of collagen and elastic fibers and are usually connected with a pedicle to the endocardial layer. Differential diagnosis with endocarditis can rely on the side of attachement: Papillary fibroelastomas are more frequently found downstream the valves, instead, endocarditis are mostly found upstream the valves. They are mostly located (>80%) on valvular surfaces, more commonly on left side cardiac valves (44% on the aortic valve and 35% on the mitral valve); therefore, in the present knowledge, papillary fibroelastomas arising from left ventricular myiocardial wall are rare and mostly anecdotally descripted. We present the case of a 78–year–old man, diabetic, with no cardiac history, hospitalized with a right capsulo–lenticular stroke. Symptomatic due to left hemiparesis, he did not undergo thrombolysis due to a delay in hospitalization of almost 24 hours. The transthoracic and then transesophageal echocardiogram showed the presence of a hyperechogenic, floating mass of approximately 3 cm at the level of the left ventricle, separate from the mitral valve and attached to the mid–distal anterior septum and the ventricular apex (Figure 1). Cardiac MRI confirmed the presence of a peduncolate left ventricular mass, isointense on cine sequences, without myocardial infiltration, isointense on T1–weighted images and mildy hyperintense on T2–weighted images, with mild uniform late–gadolinium enhancement (Figure 2). The patient underwent surgical removal of the mass: histological analysis showed multiple, branching fronds of paucicellular, avascular fibroelastic tissue lined by a single layer of endocardium, with positive stains at Weigert coloration for elastic fibers (Figure 3). Histomorphological analysis was compatible with papillary fibroelastoma. This is a very atypical case of papillary fibroelastoma, due to the large size of the mass and the intraventricular and not–valvular location, which determined its emboligenicity and which, if not removed, would have exposed the patient to an enormous risk of recurrence of stroke.

Aircraft landing gear, hydraulic actuators, gas turbine engines, helicopter dynamic components and propeller hubs all make use of hex chrome coatings. Recently, however, an electrodeposited nanocrystalline cobalt-phosphorus alloy, developed with [...]

We modified the bear cage trap with a low‐cost remotely triggered trap door and fitted the trap with a motion activated camera that relayed bear captures to researchers in real time. We built 4 modified bear cage traps and used them to capture free‐ranging American black bears (Ursus americanus) during summer 2020 on MPG Ranch in western Montana, USA. Lacking data on bear confinement time in traps from previous studies, we compared the amount of time that bears were confined in our modified traps with estimated confinement time had the same bears in our study been captured in traditional traps that were physically checked once daily at 0900, once daily at 1200, or twice daily at 0900 and 1600. We captured bears 30 times during 195 trap nights. The camera system relayed photos of all captures in real time and the remotely triggered door release was 100% successful. When we evaluated all bear captures and recaptures (n = 30), mean bear confinement time in our modified traps (4.92 hrs) was significantly lower than estimated mean confinement time had the same bears been captured in traditional traps that were checked once daily at 0900 (14.95 hrs), once daily at 1200 (10.73 hrs), or twice daily at 0900 and 1600 (7.01 hrs). For bears that were recaptured during regular trap monitoring hours (0700–1800) and remotely released without immobilization (n = 12), mean confinement time in our modified traps was <1 hr. By remotely monitoring traps, we saved an estimated US $6,580 or $13,624 in gas and staff hours during 3 months of trapping, had we physically checked traps once or twice daily, respectively. Our modified traps minimized animal confinement time, eliminated unnecessary animal immobilizations, and helped us maximize time and resource efficiencies. Our findings are relevant to bear research and management, and the technology we used can be adapted for trapping other wildlife species. [ABSTRACT FROM AUTHOR]

Among internal cooling techniques for gas turbine components, skin cooling is recognized as one of the most promising, especially thanks to the spread of additive manufacturing (AM) techniques. In this regard, several studies have tried to characterize heat transfer and pressure loss performance of additive manufactured micro-channels, as well as the impact of AM characteristic parameters, mainly in the form of building angle, and resulting surface roughness and channel shape. The open literature offers several correlations in terms of friction and heat transfer coefficient using a representative hydraulic diameter. Despite that, little attention is given on the importance of such characteristic length definition which may lead to under/over estimation of the cooling rates when correlations are used in the design. In this work, coupons featuring circular micro-channels with diameters of 0.5 and 1 mm and different building angles have been tested, to retrieve pressure losses and an average heat transfer coefficient through a lumped approach. The coupons were additive manufactured using the laser powder bed fusion technique. Exploiting the experimental survey, the impact of the considered hydraulic diameter was investigated, by comparing different approaches based on a direct measurement. An additional and new approach, aimed at the identification of an “effective” diameter, based on fluid-dynamic considerations, was also considered. The data correlation and the comparison with available correlations from different authors showed the newly proposed approach to provide superior scaling capabilities and, in turn, allowing for the development of more accurate prediction methods.

In Vittoria Facchini's utterly charming picture book story, '5 Cherries', a mother gives her two children five cherries each. One is excited; the other a little disappointed. Only five cherries? [...]

•SMAS separate the cutaneous and subcutaneous layer from the parotid tissue.•There are no differences between who received SMAS and who did not.•Gender, localization, and facial palsy are related with the aesthetic satisfaction.

Study objectives: Noninvasive ventilation, although effective as treatment for patients with acute cardiogenic pulmonary edema when prolonged for hours, is of limited use in the emergency department (ED). The aim [...]

Diabetic nephropathy has become the leading cause of uremia. Several lines of evidence suggest dietary factors other than protein intake have a substantial role in the progression of diabetic nephropathy to end-stage renal disease. The present investigation was initiated to evaluate whether a carbohydrate-restricted, low-iron-available, polyphenol-enriched (CR-LIPE) diet may delay and improve the outcome of diabetic nephropathy to a greater extent than standard protein restriction. To this aim, 191 diabetic patients, all with type 2 diabetes, were randomized to either CR-LIPE or standard protein restriction and the following outcomes monitored: doubling of serum creatinine, cumulative incidence of end-stage renal disease, and all cause mortality. Over a mean follow-up interval of 3.9 ± 1.8 years, serum creatinine concentration doubled in 19 patients on CR-LIPE (21%) and in 31 control subjects (39%) (P < 0.01). Renal replacement therapy or death occurred in 18 patients on CR-LIPE (20%) and in 31 control subjects (39%) (P < 0.01). These differences were independent from follow-up interval, sex, mean arterial blood pressure, Hb[A.sub.1c], initial renal dysfunction, and angiotensin system inhibitor use. In conclusion, CR-LIPE was 40-50% more effective than standard protein restriction in improving renal and overall survival rates., Current methods used in clinical practice to slow progression of diabetic nephropathy include angiotensin system inhibition (1-3), blood pressure and glycemic control (4,5), and isocaloric protein restriction (6). Despite these [...]

Lung ultrasound (LUS) might be comparable to chest computed tomography (CT) in detecting parenchymal and pleural pathology, and in monitoring interstitial lung disease. We aimed to describe LUS characteristics of patients during the hospitalization for COVID‐19 pneumonia, and to compare the extent of lung involvement at LUS and chest‐CT with inflammatory response and the severity of respiration impairment. During a 2‐week period, we performed LUS and chest CT in hospitalized patients affected by COVID‐19 pneumonia. Dosages of high sensitivity C‐reactive protein (HS‐CRP), d‐dimer, and interleukin‐6 (IL‐6) were also obtained. The index of lung function (P/Fratio) was calculated from the blood gas test. LUS and CT scoring were assessed using previously validated scores. Twenty‐six consecutive patients (3 women) underwent LUS 34 ± 14 days from the early symptoms. Among them, 21 underwent CT on the same day of LUS. A fair association was found between LUS and CT scores (R= 0.45, P= .049), which became stronger if the B‐lines score on LUS was not considered (R= 0.57, P= .024). LUS B‐lines score correlated with IL‐6 levels (R= 0.75, P= .011), and the number of involved lung segments detected by LUS correlated with the P/Fratio (R= 0.60, P= .019) but not with HS‐CRP and d‐Dimer levels. No correlations were found between CT scores and inflammations markers or P/F. In patients with COVID‐19 pneumonia, LUS was correlated with both the extent of the inflammatory response and the P/Fratio.

Effective treatment for metachromatic leukodystrophy (MLD) remains a substantial unmet medical need. In this study we investigated the safety and efficacy of atidarsagene autotemcel (arsa-cel) in patients with MLD.

Food operations management is the most impactful driver of global environmental challenges, including global warming, climate change, water pollution and loss of biodiversity. According to recent studies, food production systems efficiency and food loss are leading causes of environmental degradation. Although many methodologies to assess the environmental impact of food production have already been investigated, there is an urgent need to provide environmental evaluations in the fruit sector focusing on the most widespread industrial production processes and their corresponding impact. In this context, the operations management in jam production represents one of the most critical issues. Generally, in the most common jam production systems, energy-intensive treatments, including chemical substances, are adopted to extend the shelf-life of the raw materials or finished products, allowing to increase the process performance in terms of production levelling, inventory management, and market policies. In many cases, this approach compromises the sustainability of treatments, reducing the corresponding environmental performance. This paper aims to analyze the most common processes for jam production, comparing their environmental performances and the effects of the related centralized/decentralized strategies to be adopted. The potential impact categories of each process phase have been assessed. Results led to identifying the jam production from fresh fruit by adopting a decentralized production strategy, the best option considering the environmental performance under production capacity constraints

The fourth industrial transformation can create value for companies. It can bring significant improvements: those who want to be competitive in the market must implement new methods and tools to make plants efficient and productive. Industry 4.0 introduces new paradigms promoting the adoption of innovative technologies. In this context, the material handling system plays a crucial role in increasing the effectiveness and efficiency of the manufacturing systems. This paper proposes a model based on the Vehicle Routing Problem with Time Windows. The model aims to plan a dynamic routing strategy for milk-run to deliver the materials to different working stations, ensuring a materials’ distribution consistent with the time slot and minimizing the tugger trains path. A real industrial full case of a worldwide automotive company validates the model. The results of the study show benefits under economic (cost saving of 18%), environmental (allowed to reduce the distance travelled by tugger trains by around 23% for each work shift) and social (organizational development) perspectives.

Graphical abstract:

The fourth industrial revolution introduced a new paradigm in manufacturing systems. In the new production environments, operators are supported by new digital technologies, and the physical context is strictly related to the cyber one. In the digital society, recent studies show that individuals have to perform tasks based on the information gathered by a huge amount of data and the operators are employed in more cognitive than physical tasks. Therefore, the purpose of this paper consists in developing an information-based analytical framework to assess the human cognitive capacity occupancy and the human processing time of correct information when the quality performance is known. The model has been tested on case studies. The results show its effectiveness in evaluating the human mental workload imposed by the task performed and the processing speed of correct information with varying quality performance.

In Industry 4.0 (I4.0) context, procedure-guided tasks are characterised by a greater complexity due to the higher cognitive nature. On one side, increasing information processing demand and more articulated decision-making processes are required in new factories. On the other side, different I4.0 technologies are available to support workers in work environments. In this regard, the entropy measures were adopted to evaluate how the cognitive complexity required by general procedure-guided tasks changes when the I4.0 technologies are implemented. Results show that the implementation of I4.0 technologies decreases the information processing demand of the task (estimated in bit/s), reducing the cognitive effort of operators. Furthermore, the numerical simulation shows that adopting I4.0 technologies, an operator is able to perform a task 20% more complex (estimated in bit). Consequently, the study conducted allowed to predict how the information processing demand of procedure-guided tasks can be affected by implementing I4.0 technologies.

The analysis of the interaction between the swirling and liner film-cooling flows is a fundamental task for the design of turbine combustion chambers since it influences different aspects such as emissions and cooling capability. Particularly, high turbulence values, flow instabilities, and tangential velocity components induced by the swirlers deeply affect the behavior of effusion cooling jets, demanding for dedicated time-resolved near-wall analysis. The experimental setup of this work consists of a non-reactive single-sector linear combustor test rig scaled up with respect to engine dimensions; the test section was equipped with an effusion plate with standard inclined cylindrical holes to simulate the liner cooling system. The rig was instrumented with a 2D Time-Resolved Particle Image Velocimetry system, focused on different field of views. The degree of swirl is usually characterized by the swirl number, Sn, defined as the ratio of the tangential momentum to axial momentum flux. To assess the impact of such parameter on the near-wall effusion behavior, a set of three axial swirlers with swirl number equal to Sn = 0.6 − 0.8 − 1.0 were designed and tested in the experimental apparatus. An analysis of the main flow by varying the Sn was first performed in terms of average velocity, RMS, and Tu values, providing kinetic energy spectra and turbulence length scale information. Following, the analysis was focused on the near-wall regions: the effects of Sn on the coolant jets was quantified in terms of vorticity analysis and jet oscillation.

The relation between the self-reported intake of various dietary constituents and insulin-mediated glucose disposal was evaluated in 52 healthy volunteers. Insulin-mediated glucose uptake was independently associated with degree of obesity (inversely) and estimates of level of physical activity (directly). An independent relation between increased intake of vitamin A and insulin action was shown, ie, the greater the intake of vitamin A, the more effective was insulin in stimulating glucose disposal. However, there was no independent relation noted between insulin-mediated glucose disposal and estimates of the intake of carbohydrate, protein, amount or kind of fat, fiber, or vitamins C and E. Furthermore, the 20 individuals with estimates of vitamin A consumption > 10 000 IU/d had significantly lower plasma glucose (P < 0.01) and insulin (P < 0.05) responses to oral glucose, and insulin-mediated glucose disposal values that were higher (P < 0.005) than those of the 20 individuals whose estimated vitamin A intake was < 8000 IU/d. These results suggest that vitamin A intake, but not intakes of vitamin C and E, fiber, fat, or carbohydrate is associated with enhanced insulin-mediated glucose disposal. Am J Clin Nutr 1996;63:946-9.

“Macrographia”, a relatively rare symptom generally following cerebellar diseases, consists of an abnormally large handwriting. The case reported in the present investigation shows several outstanding features. First, it is of the progressive variety, letters increase in size as one goes through the word towards the lower-right portion of space. Moreover, it is limited to one allographic variety, that is, block letters. This phenomenon is previously unreported, all allographic varieties being usually equally affected. Finally, no prominent cerebellar or basal ganglia abnormality could be demonstrated with structural MRI or PET. From a cognitive point of view, a peculiar combination of spatial attention, executive function and working memory deficits is proposed to account for the progressive misalignment and elongation of individual letters when specifically writing in block prints. From an anatomical perspective, the pattern of multifocal lesions, encompassing multiple cortical areas in both hemispheres and the corpus callosum, may support this multi-componential interpretation of the reported phenomenon.

Pregnant women may lose a significant amount of calcium to the fetus during the third trimester. Researchers used ultrasonography to measure the amount of calcium in the heel bones of 10 pregnant women from the 14th to the 38th weeks of pregnancy. Bone density was found to remain stable during the first and second trimesters, then to drop during the third trimester. The pregnant woman's body may release calcium from its bones to send it across the placenta to the fetus, whose bone structure is growing rapidly during the last trimester.

Native human skin has been reported in the literature as being an important experimental model for studying skin biology. Studies performed by our group have shown that ex vivoskin, from elective plastic surgery, maintains the biological characteristics of native skin under specific culture conditions. As such, it might be a feasible model for the safety and efficacy testing of topical substances. While Brazil is at the forefront of global regulation implementation, Brazilian researchers are not always able to transfer certain widely used protocols to their laboratories, particularly protocols that involve the use of reconstructed tissues with limited viability, such as those for skin corrosion (OECD TG 431) and irritation testing (OECD TG 439). In this study, we investigated the applicability of the ex vivoskin model to the evaluation of irritation and corrosion potential of a number of proficiency substances described in TG 431 and TG 439. The skin fragments were standardised in size and diameter, and placed into cell culture inserts. The experimental protocol was conducted according to TG 431 and TG 439. The results obtained show that ex vivoskin could represent a promising tool for the evaluation of irritation and corrosion potential of substances (subject to inclusion and exclusion criteria), as recommended by OECD guidelines. While this is a proof-of-concept study, the use of ex vivoskin should be considered for such testing.