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In this study we assess periodicities in nitrogen dioxide levels at a location in Los Angeles using a novel Variable Bandpass Periodic Block Bootstrap (VBPBB) method resulting in confidence interval bands for the periodic mean. Nitrogen dioxide (NO2) is an air pollutant primarily produced by the combustion of fossil fuels by power plants and vehicles with internal combustion engines which has been linked with a variety of adverse health outcomes including dementia, breast cancer, decreased cognitive function, increased susceptibility to Covid-19, cardiovascular and respiratory mortality. Previous analysis methods such as block bootstrapping can obscure periodically correlated patterns in time series. The sampling destroys the correlation observed in the data for patterns of different periods, such as the daily, weekly and yearly patterns of nitrogen dioxide levels we wish to investigate. We use the VBPBB method to isolate significant periodicities using a band pass filter before bootstrapping so that the correlations between the data are preserved. Confidence interval bands for VBPBB are compared against existing block bootstrapping. The resulting narrower confidence interval bands created by VBPBB show a significant annual fluctuation in nitrogen dioxide levels while the existing methods do not show it as clearly. Better characterization of pollution patterns will aid in pollution reduction efforts by allowing us to pinpoint times of highest risk and direct mitigation efforts where they will have the greatest impact. This technique exhibits potential for future applications to other areas of environmental and health interest and concern. [ABSTRACT FROM AUTHOR]

Background: Dyadic interventions for health behaviour change involving the romantic partner are promising. However, it often remains unclear how exactly the partner is involved in dyadic interventions. We propose a novel compendium of dyadic intervention techniques (DITs) that facilitates systematic description of dyadic interventions in terms of who performs what for whom during intervention delivery and subsequent implementation. Objective: We aimed to systematically characterise dyadic interventions along their degree of partner involvement and to provide a comprehensive list of DITs used in dyadic interventions with romantic partners. Methods: We systematically reviewed dyadic health behaviour change interventions with controlled designs. We included 165 studies describing 122 distinct dyadic interventions with romantic partners. Interventions were classified along their degree of partner involvement, 160 DITs were extracted, and their frequencies of use counted. Results: The majority of interventions (n = 90 , 74%) explicitly instructed partners to interact. Half of the DITs were performed jointly by the couple and also targeted the couple. Mostly, couples were instructed to jointly practice communication skills and to jointly perform problem solving for the couple. Discussion: The present review contributes to the development of a shared and systematic way of describing dyadic interventions to facilitate cumulation of evidence. [ABSTRACT FROM AUTHOR]

Viral co-infections are frequently observed among children, but whether specific viral interactions enhance or diminish the severity of respiratory disease is still controversial. This study aimed to investigate the type of viral mono- and co-infections by also evaluating viral correlations in 3525 respiratory samples from 3525 pediatric in/outpatients screened by the Allplex Respiratory Panel Assays and with a Severe Acute Respiratory Syndrome-COronaVirus 2 (SARS-CoV-2) test available. Overall, viral co-infections were detected in 37.8% of patients and were more frequently observed in specimens from children with lower respiratory tract infections compared to those with upper respiratory tract infections (47.1% vs. 36.0%, p = 0.003). SARS-CoV-2 and influenza A were more commonly detected in mono-infections, whereas human bocavirus showed the highest co-infection rate (87.8% in co-infection). After analyzing viral pairings using Spearman's correlation test, it was noted that SARS-CoV-2 was negatively associated with all other respiratory viruses, whereas a markedly significant positive correlation (p < 0.001) was observed for five viral pairings (involving adenovirus/human bocavirus/human enterovirus/metapneumoviruses/rhinovirus). The correlation between co-infection and clinical outcome may be linked to the type of virus(es) involved in the co-infection rather than simple co-presence. Further studies dedicated to this important point are needed, since it has obvious implications from a diagnostic and clinical point of view. [ABSTRACT FROM AUTHOR]

Background. Parkinson's disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, and muscle rigidity. Visual disturbances have been also described among non-motor features. Objective. We aimed to investigate the structural and vascular changes in the retinal and choroidal vascular networks, and to assess any relationship with motor and non-motor symptoms (NMS) in PD patients. Methods. Ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), and subfoveal choroidal thickness (SFCT) were examined using spectral domain-optical coherence tomography (SD-OCT). The vessel density (VD) of retinal and choriocapillary vascular networks in macular area and the foveal avascular zone (FAZ) area were evaluated by OCT angiography (OCTA). All patients underwent clinical evaluation using motor section of the Unified PD Rating Scale (UPDRS-III) and the Hoehn and Yahr (HY) scale. Results. A total of 48 eyes from 24 PD patients and 50 eyes from 25 controls were assessed. At SD-OCT, GCC and RNFL were more significantly thin in patients compared to controls. At OCTA exam, PD subjects showed lower values in VD of superficial capillary plexus (SCP) and radial peripapillary capillary plexus in comparison to controls, whereas FAZ area resulted in a significant increase in the patient group. We found a negative correlation between the age at onset and VD of SCP, and between HY score and RNFL thickness and FAZ. UPDRS-III score was negatively correlated with VD of deep capillary plexus. Discussion. The impairment of retinal structure and microvasculature seems to correlate with disease severity and progression in PD. Retinal anomalies can be considered as non-motor manifestations that could occur already in the early stage of the disease. [ABSTRACT FROM AUTHOR]

Aims: Recent studies have shown that lung ultrasound‐assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH). Methods and results: All patients referred for suspicion of PAH in a tertiary centre from January 2020 to December 2022 underwent a complete diagnostic work‐up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B‐lines using an 8‐site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53 ± 13 years; 71% female). World Health Organization functional classes I, II, and III were found in 2%, 52%, and 46% of them, respectively. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) was 377 pg/ml (interquartile range [IQR] 218–906). B‐lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR 1–5]. At univariable analysis, B‐lines were positively correlated with male sex, age, NT‐proBNP, systolic pulmonary artery pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end‐diastolic volume and tricuspid annular plane systolic excursion (TAPSE), and negatively with cardiac output and stroke volume. At multivariable analysis, RAP (p < 0.001), TAPSE/sPAP (p = 0.001), and NT‐proBNP (p = 0.04) were independent predictors of B‐lines. Conclusion: Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricular to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow. [ABSTRACT FROM AUTHOR]

Context. The intrinsic variability due to the magnetic activity of young active stars is one of the main challenges in detecting and characterising exoplanets. The stellar activity is responsible for jitter effects observed both in photometric and spectroscopic observations that can impact our planetary detection sensitivity. Aims. We present a method able to model the stellar photosphere and its surface inhomogeneities (starspots) in young, active, and fast-rotating stars based on the cross-correlation function (CCF) technique, and we extract information about the spot configuration of the star. Methods. We developed Spot CCF, a tool able to model the deformation of the CCF profile due to the presence of multiple spots on the stellar surface. Within the Global Architecture of Planetary Systems (GAPS) Project at the Telescopio Nazionale Galileo, we analysed more than 300 spectra of the young planet-hosting star V1298 Tau provided by the HARPS-N high-resolution spectrograph. By applying the SpotCCF model to the CCFs, we extracted the spot configuration (latitude, longitude, and projected filling factor) of this star, and provide a new radial velocity (RV) time series for this target. Results. We find that the features identified in the CCF profiles of V1298 Tau are modulated by the stellar rotation, supporting our assumption that they are caused by starspots. The analysis suggests a differential rotation velocity of the star with lower rotation at higher latitudes. Also, we find that SpotCCF provides an improvement in RV extraction, with a significantly lower dispersion with respect to the commonly used pipelines. This allows mitigation of the stellar activity contribution modulated with stellar rotation. A detection sensitivity test, involving the direct injection of a planetary signal into the data, confirms that the SpotCCF model improves the sensitivity and ability to recover planetary signals. Conclusions. Our method enables us to model the stellar photosphere and extract the spot configuration of young, active, and rapidly rotating stars. It also allows the extraction of optimised RV time series, thereby enhancing our detection capabilities for new exoplanets and advancing our understanding of stellar activity. [ABSTRACT FROM AUTHOR]

Purpose: Optimal use of bone-modifying agents (BMAs) in patients with bone metastases from solid tumors is uncertain in some aspects: the drug choice; the planned treatment duration and long-term therapy; the prevention and management of possible side effects, including renal toxicity, hypocalcaemia, and medication-related osteonecrosis of the jaw (MRONJ). Methods: Italian oncologists were invited to fulfil a 24-question web survey about prescription of BMAs for bone metastases of breast cancer, prostate cancer, and other solid tumors. Prevention and management of side effects were also investigated. Results: Answers of 191 oncologists were collected. BMAs are usually prescribed at the time of diagnosis of bone metastases by 87.0% (breast cancer) and 76.1% (solid tumors except breast and prostate cancers) of oncologists; the decision is more articulated for prostate cancer (endocrine-sensitive versus castration-resistant). The creatinine level (32.3%), the availability of patient venous access (15.8%), and the type of primary neoplasm (13.6%) are the most reported factors involved in choice between bisphosphonates and denosumab. Zoledronic acid every 3 months was considered as a valid alternative to monthly administration by 94% of Italian oncologists. Oncologists reported a good confidence with measures aimed to prevent MRONJ, whereas uncertainness about prevention and management of hypocalcemia was registered. Conclusion: Italian oncologists showed a high attitude in prescribing bisphosphonates or denosumab at the time of diagnosis of bone metastases, with a large application of preventive measures of side effects. Further studies are needed to investigate some controversial aspects, such as optimal drug treatment duration and long-term drug schedules. [ABSTRACT FROM AUTHOR]

Quality of control arms in randomized clinical trials implies also optimal postprotocol treatment. Meta‐research studies highlighting biases of the published literature contribute to improving design and conduct of future studies. [ABSTRACT FROM AUTHOR]

This multicenter cross-sectional study explored the responsiveness of Mental Health Services (MHS) to two years of COVID-19 emergency in Italy. Specifically, the study explored the ability of staff to: acknowledge users' capabilities and value teamwork; reinvent the service and maintain/introduce good practices; and, acknowledge the positive aspects of the pandemic experience. These aspects were investigated in relation to socio-demographic and professional variables. Professionals from 17 MHS of 15 Italian Regions completed an online questionnaire on the MHS transformation during COVID-19. Data were collected at the end of the national health emergency (March 1-April 30, 2022). Most of the 1077 participants said they: paid more attention to users' physical health; revised treatment plans; mediated between user needs and safe work procedures; revalued the importance of gestures and habits; discovered unexpected personal resources in users; and, found positive aspects in the COVID-19 experience. The multivariate analyses showed significant differences in staff opinions related to gender, workplace, professional role, and geographic area of the MHS, covarying with staff work experience. Compared to male staff, female staff perceived MHS as more flexible and capable to maintain best practices, and female staff acknowledged more capabilities to the users. Compared to central and northern Italy staff, southern Italy staff gave more values to teamwork, perceived MHS as more capable to maintain best practices and acknowledged higher positive transformations. These findings may be useful for planning community-oriented MHS in the post-pandemic period, taking into account both the experience gained by staff and the MHS process of adaptation. [ABSTRACT FROM AUTHOR]

(1) Background: The prompt diagnosis of anterior mediastinal lesions is a challenge due to their often being categorized as malignant tumours. Ultrasound-guided Transthoracic Core Needle Biopsy (US–TCNB) is an innovative technique that is arousing increasing interest in clinical practice. However, studies in this area are still scarce. This study aims to compare the diagnostic accuracy and complication rate of US–TCNB with those of traditional surgical methods—Anterior Mediastinotomy and Video Assisted Thoracoscopic Surgery (VATS)—in patients with anterior mediastinal lesions. (2) Methods: This retrospective study involved patients evaluated between January 2011 and December 2021 who had undergone US–TCNB at the Interdepartmental Unit of Internal and Interventional Ultrasound, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy. Personal data, diagnostic questions, and technical information concerning the bioptic procedure, periprocedural complications and histological reports were collected. (3) Results: Eighty-three patients were included in the analysis. Histological examination was performed in 78 cases, with an overall diagnostic accuracy of 94.0% (sensitivity 94%; specificity 100%). Only in 5 patients was a diagnosis not achieved. Complications occurred in 2 patients who were quickly identified and properly treated without need of hospitalization. The accuracy of US–TCNB was comparable to the performance of the main traditional diagnostic alternatives (95.3% for anterior mediastinotomy, and 98.4% for VATS), with a much lower complication rate (2.4% vs. 3–16%). The outpatient setting offered the additional advantage of saving resources. (4) Conclusions: a US-guided needle biopsy can be considered effective and safe, and in the near future it may become the procedure of choice for diagnosing anterior mediastinal lesions in selected patients. [ABSTRACT FROM AUTHOR]

Background: In addition to improving survival outcomes, new oncology treatments should lead to amelioration of patients' quality of life (QoL). Herein, we examined whether QoL results correlated with PFS and OS outcomes in phase III randomized controlled trials (RCTs) investigating new systemic treatments in metastatic non-small cell lung cancer (NSCLC). Methods: The systematic search of PubMed was conducted in October 2022. We identified 81 RCTs testing novel drugs in metastatic NSCLC and published in the English language in a PubMed-indexed journal between 2012 and 2021. Only trials reporting QoL results and at least one survival outcome between OS and PFS were selected. For each RCT, we assessed whether global QoL was "superior," "inferior," or with "non-statistically significant difference" in the experimental arm compared to the control arm. Results: Experimental treatments led to superior QoL in 30 (37.0%) RCTs and inferior QoL in 3 (3.7%) RCTs. In the remaining 48 (59.3%) RCTs, a statistically significant difference between the experimental and control arms was not found. Of note, we found a statistically significant association between QoL and PFS improvements (X2 = 3.93, p = 0.0473). In more detail, this association was not significant in trials testing immunotherapy or chemotherapy. On the contrary, in RCTs testing target therapies, QoL results positively correlated with PFS outcomes (p = 0.0196). This association was even stronger in the 32 trials testing EGFR or ALK inhibitors (p = 0.0077). On the other hand, QoL results did not positively correlate with OS outcomes (X2 = 0.81, p = 0.368). Furthermore, we found that experimental treatments led to superior QoL in 27/57 (47.4%) trials with positive results and in 3/24 (12.5%) RCTs with negative results (p = 0.0028). Finally, we analyzed how QoL data were described in publications of RCTs in which QoL outcomes were not improved (n = 51). We found that a favorable description of QoL results was associated with sponsorship by industries (p = 0.0232). Conclusions: Our study reveals a positive association of QoL results with PFS outcomes in RCTs testing novel treatments in metastatic NSCLC. This association is particularly evident for target therapies. These findings further emphasize the relevance of an accurate assessment of QoL in RCTs in NSCLC. [ABSTRACT FROM AUTHOR]

Recently, many cancer drugs have been approved by regulatory agencies based on single-arm studies, where analysis of quality of life (QoL) and patient-reported outcomes (PROs) is not a direct comparison with the standard, but the simple description of changes versus baseline and trends over time. This analysis can be potentially biased by missing data: QoL level could be overestimated, and symptoms underestimated. Caution is needed to avoid that a methodologically weak evidence in PROs and QoL data is overrated, if not for the drug approval, for the interpretation of data by scientific community and the communication with patients. PROs experts should be involved in planning, conduction, and interpretation of analyses. [ABSTRACT FROM AUTHOR]

Hazardous Natural events can cascade into Technological accidental scenarios (so called NaTech accidents). The occurrence of these accidents can degrade the performance of the preventive and mitigative safety barriers installed in the technological plants. Such performance degradation is typically assessed by expert judgement, without considering the effect of the magnitude of the natural hazard, nor its increasing frequency of occurrence in view of climate change. In this work, a novel sensitivity analysis framework is developed to identify the safety barriers whose performance degradation is most critical and thus needs careful modeling for realistic risk assessment. The framework is based on the calculation of a set of sensitivity measures, namely the Beta, the Conditional Value at Risk (CVaR) and the Value of Information (VoI), ● and their use to prioritize the safety barriers with respect to the need of: ● accounting for performance degradation during an accidental scenario; ● planning investments for further characterization of the safety barrier performance. An application is shown with respect to a case study of literature that consists of a chemical facility equipped with five safety barriers (of three different types, active, passive and procedural). NaTech scenarios can occur, triggered by floods and earthquakes. The results obtained with the Beta measure indicate that two-out-of-five barriers (one active and one passive) deserve accurate modelling of the performance degradation due to natural events. An additional outcome is that in the case study considered, both CVaR and VoI rank the passive barrier as the most effective in mitigating the scenarios escalation: therefore, this barrier is the one for which the decision maker could decide to invest resources for improving the characterization of its performance to obtain a more realistic assessment of the risk. [ABSTRACT FROM AUTHOR]

Background: Preoperative diagnosis of periprosthetic joint infections (PJIs) poses an unmet clinical challenge. The long pentraxin PTX3 is a component of the innate immune system involved in infection immunity. This study evaluated the potential of synovial and plasmatic PTX3 in the diagnosis of hip and knee PJIs. Methods: Consecutive total hip and knee arthroplasty (THA/TKA) revisions were prospectively included and classified as septic or aseptic according to the European Bone and Joint Infection Society (EBJIS) and Musculoskeletal Infection Society (MSIS) criteria. The concentration of PTX3 in plasma and synovial fluid samples was measured with ELISA. The AUC, threshold value, sensitivity, specificity, and positive and negative likelihood ratios were calculated using the ROC (receiver operating characteristic) curve method. Results: The study population included 128 patients (94 THAs; 34 TKAs). The AUC of the synovial PTX3 based on EBJIS criteria was 0.85 (p < 0.0001), with a sensitivity of 81.13% and a specificity of 93.33%. The AUC based on MSIS criteria was 0.95 (p < 0.001), with a sensitivity of 91.43% and a specificity of 89.25%. Plasmatic PTX3 failed to discriminate infected from non-infected patients. Conclusions: Synovial PTX3 demonstrated an excellent diagnostic potential in hip and knee PJIs, with a very high specificity irrespective of the diagnostic criteria for PJI. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the effect of early chelation therapy (≤ 3 years) with a variety of chelating agents on age at menarche and menstrual characteristics in patients with transfusiondependent thalassemia (TDT). Design: A retrospective multicenter study promoted by the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A). Setting: Eight of 13 International Thalassemia Centers (61.5%) in the ICET-A Network participated. Patients: Fifty-seven female TDT patients, aged 11 to 26 years, and with early iron chelation therapy, were eligible for the present study. They were enrolled from one center from Iran (33 patients), 3 centers from Bulgaria (9), 1 from Greece (8), one from Oman (4), 1 from Cyprus (2), and 1 from Italy (1). Seven patients were excluded, four still prepubertal (age 12-14 years) and 3 with primary amenorrhea. Therefore 50 patients were finally enrolled. Results: All fifty TDT patients developed spontaneous menarche at a mean age of 14.2 ± 2.24 years (range 9 - 20). A significant positive correlation was observed between age at menarche and serum ferritin levels (r: 0. 41, p=0.005). Regular menstrual cycles were reported from 32 (64%) patients, of whom 28 (83.3%) get menarche at age ≤ 14 years. Complications were more frequent in patients older than 14 years at menarche and in those with secondary amenorrhea. Conclusions: Age at menarche greater than 14 years was a forerunner of menstrual irregularities and associated complications in 36% of patients despite precocious chelation therapy. The poor adherence to treatment, to be demonstrated in future studies, could explain the finding. [ABSTRACT FROM AUTHOR]

Background: Different methods to measure tissue perfusion are available in equine neonatology, but they are not representative of microvascular derangements. Objective: To evaluate the feasibility of the sidestream dark‐field (SDF) capillaroscopy to visualize the capillary microvasculature in conscious newborn foals, the differences between two imaging sites and times of measurements, and the measurements' reproducibility. Methods: Seventeen healthy newborn foals were enrolled. Three sites at the upper and lower lip mucosa were assessed by SDF, using a hand‐held capiscope, at 24 h and at 4–5 days after birth. Videos were assessed independently by two observers for quality and for semiquantitative calculation of microvascular parameters, including vascular density (VD), microvascular flow index (MFI), proportion of perfused vessels (PPV), and functional capillary density (FCD). Data were analyzed using unpaired and paired Student's T‐tests to assess differences between sites and time‐points. Bland–Altman plots and intraclass correlation coefficient (ICC) were used to assess measurement reproducibility. Results: Differences were found between the upper and the lower lip for VD at both 24 h and 4–5 days, and for FCD at 24 h, and between the two time‐points for PPV at the lower lip. ICC for measurement reproducibility was good for all parameters (0.64–0.79) for the lower lip, and was good for VD and FCD (0,76–0,79) and fair to moderate for MFI and PPV (0.31–0.41) for the upper lip. Conclusions: Measurement of the capillary microvasculature is feasible in the conscious newborn foal. The lower lip has the best measurement reproducibility. Further investigations are warranted in cardiovascularly compromised cases, particularly in septic foals. [ABSTRACT FROM AUTHOR]

Thermofluorochromic materials exhibit tunable fluorescence emission on heating or cooling. They are highly desirable for applications ranging from temperature sensing to high-security anti-counterfeiting. Luminescent matrices based on liquid crystals are very promising, particularly those based on liquid crystals with intrinsic fluorescence. However, only a few examples have been reported, suggesting ample margins for development in the field, due to the wide range of fluorophores and supramolecular organizations to be explored. Moreover, thermofluorochromic liquid crystals can be tailored with further functionalities to afford multi-stimuli responsive materials. For the first time, herein we report the thermofluorochromism of thienoviologen liquid crystals, already known to show bulk electrochromism and electrofluorochromism. In particular, we studied their photophysics in the 25 °C–220 °C range and as a function of the length of the N-linear alkyl chains, m (9 ≤ m ≤ 12 C atoms), and the type of anion, X (X = OTs-, OTf-, BF4-, NTf2-). Interestingly, by changing the parameters m, X and T, their fluorescence can be finely tuned in the whole visible spectral range up to the NIR, by switching among different mesophases. Importantly, by fixing the structural parameters m and X, an interesting thermofluorochromism can be achieved for each thienoviologen in a homologous series, leading to a switch of the emitted light from red to green and from white to blue as a consequence of the temperature-induced variation in the supramolecular interactions in the self-assembled phases. [ABSTRACT FROM AUTHOR]

• The thermomechanical performances of the DEMO WCLL BB equipped with helicoidal DWTs have been investigated. • Different nominal and off-normal steady state loading scenarios have been selected. • Dedicated FEM models of the equatorial region of the COB segment have been set-up. • Results have allowed predicting a quite promising behaviour in view of the RCC-MRx code. • The deformation predicted within the tubes is compliant with the allocated space reservation. With the aim of improving the EU-DEMO breeding blanket (BB) system performances, variants to the reference design are presently under investigation in the EUROfusion activities. Among them, a novel layout for the double-walled tubes (DWTs) aimed at cooling the breeding zone is being studied for the Water-Cooled Lead Lithium (WCLL) BB concept. The new DWTs configuration consists of 6 couples of helical-shaped DWTs, with each tubes couple being positioned in a slot defined by the radial-poloidal stiffening plates (SPs). The adoption of the helicoidal tubes layout shall allow reducing the thermal hotspots in the BB structural material, being beneficial also in terms of thermal stress. Hence, a structural analysis of the equatorial region of the WCLL BB central outboard blanket segment has been performed and presented in this work. The structural assessment has been conducted under various loading scenarios, including Normal Operation (NO), with nominal and design pressure values, and NO scenario considering buoyancy effects induced by the liquid breeder. All these scenarios assumed the same previously obtained thermal field to predict displacements and stress fields. Subsequently, a stress linearization procedure has been performed in some critical regions of the structure, which allows comparing the stress values obtained with the criteria prescribed by the reference design standard RCC-MRx. The outcomes derived from this evaluation, in terms of stresses and displacements, seem very promising. However, some contact regions have been identified in the tubes, necessitating careful consideration of geometric modifications in future analyses. Nevertheless, the obtained results clearly show that the proposed layout is worthy to be further assessed. A theoretical–numerical approach based on the Finite Element Method (FEM) was followed adopting the Ansys commercial code. [ABSTRACT FROM AUTHOR]

A series of novel cationic curcumin-based Pt(II) complexes with neutral (N^N) ligands and triflate anions as counterions, [(N^N)Pt(curc)]CF3SO3, 1–4, were synthesised and fully characterised. The antioxidant radical scavenging activity of complexes 1–4 was measured spectrophotometrically using DPPH as the internal probe. Computational strategies have been exploited to ascertain the mechanism of antioxidant action of curcumin (H(curc)) and its Pt(II) complexes. Finally, compounds 1–4 were tested in vitro for their growth inhibitory activity against two bacteria (Staphylococcus aureus and Escherichia coli) by the disk diffusion technique at different Pt(II) complex solution concentrations. The effect of the complexation of H(curc) was investigated. [ABSTRACT FROM AUTHOR]

Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli—such as exercise, cold exposure, and drug treatment—white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the 'browning of WAT'. We evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity. [ABSTRACT FROM AUTHOR]

Chikungunya virus (CHIKV) is an arthropod-borne virus (arbovirus) transmitted by Aedes mosquitoes. The human infection usually manifests as a febrile and incapacitating arthritogenic illness, self-limiting and non-lethal. However, since 2013, CHIKV spreading through the tropics and to the Americas was accompanied by an increasing number of cases of atypical disease presentation, namely severe neuropathies and neonatal infection due to intrapartum vertical transmission. The pathophysiological mechanisms underlying these conditions have not been fully elucidated. However, arbovirus intrahost genetic diversity is thought to be linked to viral pathogenesis. To determine whether particular viral variants could be somehow associated, we analyzed the intrahost genetic diversity of CHIKV in three infected patients with neurological manifestations and three mothers infected during the intrapartum period, as well as their babies following vertical transmission. No statistically supported differences were observed for the genetic variability (nucleotide substitutions/gene length) along the genome between the groups. However, the newborn and cerebrospinal fluid samples (corresponding to virus passed through the placenta and/or the blood–brain barrier (BBB)) presented a different composition of their intrahost mutant ensembles compared to maternal or patient serum samples, even when concurrent. This finding could be consistent with the unidirectional virus transmission through these barriers, and the effect of selective bottlenecks during the transmission event. In addition, a higher proportion of defective variants (insertions/deletions and stop codons) was detected in the CSF and maternal samples and those were mainly distributed within the viral non-structural genes. Since defective viral genomes in RNA viruses are known to contribute to the outcome of acute viral infections and influence disease severity, their role in these atypical cases should be further investigated. Finally, with the in silico approach adopted, we detected no relevant non-conservative mutational pattern that could provide any hint of the pathophysiological mechanisms underlying these atypical cases. The present analysis represents a unique contribution to our understanding of the transmission events in these cases and generates hypotheses regarding underlying mechanisms, that can be explored further. [ABSTRACT FROM AUTHOR]

• This ESMO Guideline provides key recommendations on the role of PROMs during the care of patients with cancer. • It covers the use of PROMs in patients with cancer from the start of active treatment during follow-up to the end of life. • Recommendations are based on available scientific evidence and the authors' collective expert consensus. • Authorship includes a multidisciplinary group of experts from Europe, North America, Asia and Australia. [ABSTRACT FROM AUTHOR]

In recent years, there has been a growing interest in the design, development and commercialization of nuclear power Small Modular Reactors (SMRs). Actual SMR designs cover the full spectrum of nuclear reactor technologies, including water-, gas-, liquid-metal-, and molten-salt-cooled. Despite physical and technological differences, SMRs share some relevant design features, such as small size, modularity, inherent and passive safety systems. These features are expected to enhance availability, recoverability, promptness and robustness, thereby contributing to the resilience of power supply. Thanks to the peculiar design features of SMRs, they are likely to satisfy a number of Functional Requirements (FRs) for this objective, namely: (i) low vulnerability to external hazards; (ii) natural circulation of primary coolant; (iii) prompt, unlimited and independent core cooling under shutdown conditions; (iv) shutdown avoidance in response to variations of the offsite power supply quality and electrical load; (v) island mode operation; (vi) robust load-following; (vii) independent, self-cranking start. These make advanced Nuclear Power Plants (aNPPs) comprised of SMRs perfect candidates to withstand a broader range of natural disruptions and to recover faster from them, compared to conventional Nuclear Power Plants (cNPPs), thus rendering them a major potential asset for guaranteeing resilience and security of power supply. The review focuses on Natural Technological (NaTech) events that impact a typical Integrated Energy System (IESs) within which SMRs are embedded: IESs are, indeed, being developed to integrate different power generation plants with gas facilities, through gas and electricity infrastructures, because they are expected to bring increased security and resilience of power supply, as shown in the qualitative case study presented. [ABSTRACT FROM AUTHOR]

The Computational Risk Assessment (CRA) of Cyber-Physical Systems (CPSs) calls for the analysis of accidental scenarios emerging from the complexities and interdependencies typical of CPSs. Generating these scenarios via crude Monte Carlo Simulation (MCS) is impractical due to the high computational demand of simulation codes of CPSs, considering the combinatorial number of possible scenarios. In this paper, we tailor the use of Repetitive Simulation Trials After Reaching Thresholds (RESTART), a rare-event simulation method of literature, to efficiently generate relevant accidental scenarios. The tailored RESTART is guided by a dynamic Importance Function (IF) originally introduced here to dynamically characterize the relevance of the scenarios with reference to the current topology of the CPS and the susceptibility of its components. Two case studies of increasing complexity are considered: a single power grid and a CPS consisting of an Integrated Power and Telecommunication (IP&TLC) infrastructure. Results show that RESTART mines out more relevant scenarios than crude MCS for a number of different IFs based on vulnerability metrics of literature, and thus particularly efficiently when the novel IF is adopted. [ABSTRACT FROM AUTHOR]

In the nuclear industry, Severe Accident Management Guidelines (SAMGs) are developed with the objective of providing prescriptive actions for mitigating the consequences of Nuclear Power Plant (NPP) accidents. These guidelines are defined with respect to a set of expert-based prototypical severe accident scenarios and are symptom-based, i.e., they relate to the values of specific monitored plant parameters. Expert-based SAMGs might fail to deal with non-prototypical scenarios, i.e., scenarios not considered a priori by the experts. To address this issue, in this paper we propose a methodology based on Dynamic Bayesian Networks (DBNs) to support operators decision-making for avoiding the escalation of severe accidents to non-prototypical scenarios. The methodology is based on the integration of condition monitoring data into a DBN to allow it to i) infer the current Plant Operating Condition (POC), Initiating Event (IE), and NPP safety barriers Damage State (DS), ii) predict the grace time (GT) available to carry out mitigative actions, and iii) evaluate the effectiveness of the alternative candidate mitigative actions taking into account the safety barriers estimated DS and the predicted available GT. The proposed methodology is exemplified on a Loss of Coolant Accident (LOCA) in a WWER-1000. [ABSTRACT FROM AUTHOR]

• IUQ methodologies are employed to estimate the uncertainties affecting T-H codes through SETs data. • A distribution based global SA is proposed to tailor the IUQ to subregions of segmented ICs&BCs. • The tailoring of the IUQ is exemplified on two SETs, i.e., Sozzi-Sutherland and Super Moby Dick. • The novel IUQ methodology is superior to traditional IUQ for SETs highly sensitive to ICs&BCs. Within the Best Estimate Plus Uncertainty framework for the safety analysis of Nuclear Power Plants, the quantification of the uncertainties affecting the Thermal-Hydraulics (T-H) codes used is crucial. For this, Inverse Uncertainty Quantification (IUQ) methodologies are being developed for determining the probability density functions of relevant T-H codes input parameters, based on experimental data from Separate Effect Tests (SETs) experimental facilities. In practice, IUQ is challenged by the large range of variability of the experimental data in terms of Initial and Boundary Conditions (ICs & BCs), because the experimental campaigns are designed to cover the widest possible domain of conditions with the smallest number of experiments, so that same or similar ICs and BCs are seldomly repeated. To address this issue, we propose to use global sensitivity analysis, to tailor the IUQ on specific sub-regions described by segmented ICs & BCs domains. The methodology proposed is exemplified on two SETs, namely Sozzi-Sutherland and Super Moby Dick, whose experimental databases have been made available in the ATRIUM (Application Tests for Realization of Inverse Uncertainty quantification and validation Methodologies in thermal hydraulics) project promoted by the OECD/NEA/CSNI. The results obtained are superior to those of traditional IUQ methodologies for models highly sensitive to ICs & BCs. [ABSTRACT FROM AUTHOR]

A novel method to enhance and control bubble nucleation in poly(l‐lactic acid) (PLLA) foaming, not relying on external nucleating agents, is presented. Amorphous PLLA is annealed at temperatures close to its glass transition, to allow local alignment of polymer chains in the form of nanosized aggregates, called homogeneous crystal nuclei (HCN). PLLA containing HCN is then foamed after sorption of CO2 at 120 °C and 10 MPa. Under the chosen experimental conditions, HCN can promote growth of PLLA spherulites that can be controlled by thermal‐pressure history. Foam morphology is strongly affected by the presence of HCN, which act as heterogeneous nucleation sites for bubbles. Resulting foams are characterized by a bimodal morphology, with bubbles of about 50–70 µm in diameter developed in the bulk, and much smaller cells of few µm, grown upon pre‐existing crystal aggregates. The method detailed here to attain PLLA foams with tailored morphology can be exploited also for other semicrystalline polymers. [ABSTRACT FROM AUTHOR]

To assess the performance of the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria in stratifying the risk of bleeding and ischaemic events after percutaneous coronary intervention (PCI). MEDLINE, COCHRANE, Web of Sciences, and SCOPUS were searched for studies aimed at validating the ARC-HBR criteria in patients treated with PCI. The primary outcome measure of this meta-analysis was major bleeding. The analysis included 10 studies encompassing 67,862 patients undergoing PCI; the HBR definition was fulfilled in 44.7% of the cases. The risk of major bleeding was significantly higher in HBR vs. Non-HBR group (RR, 2.56, 95% CI 2.28–2.89). The average C-statistic was 0.64 (95% CI 0.60–0.68), indicating modest discrimination. The risk of intracranial hemorrhage, gastrointestinal bleeding, fatal bleeding, ischaemic stroke, cardiac death and all-cause death was higher in HBR vs. Non-HBR group. Despite a higher incidence of myocardial infarction and stent thrombosis in patients deemed at HBR, the rate of target lesion revascularization was comparable between groups (RR, 1.01, 95% CI 0.88–1.16). The mean effect size for the cumulative incidence of major bleeding exceeded the HBR cut-off value of 4% for all major criteria except one, and for two out of six minor criteria, namely age ≥ 75 years and moderate CKD. The ARC-HBR definition identifies patients at higher risk of major bleeding and other adverse cardiovascular events after PCI. Almost all major criteria, but also two of the minor criteria, were individually associated with rates of major bleeding above 4% thus fulfilling the definition of major HBR criteria. • The ARC-HBR definition identifies patients at high risk of adverse events. • The ARC-HBR definition is associated with a modest discrimination for major bleedings. • Higher rate of MI and ST does not correspond to higher rate of TLR in HBR patients. • Some minor criteria fulfill the definition of major HBR criteria. [ABSTRACT FROM AUTHOR]

Background: Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic. Method: Cohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls. Results: SARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interaction p‐value = 0.03). Although SARS‐CoV‐2 positive patients had a five‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a). Conclusions: SARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a). [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) is a recently recognized viral infective disease which can be complicated by acute respiratory stress syndrome (ARDS) and cardiovascular complications including severe arrhythmias, acute coronary syndromes, myocarditis and pulmonary embolism. The aim of the present study was to identify the clinical conditions and echocardiographic parameters associated with in‐hospital mortality in COVID‐19. Methods: This is a multicentre retrospective observational study including seven Italian centres. Patients hospitalized with COVID‐19 from 1 March to 22 April 2020 were included into study population. The association between baseline variables and risk of in‐hospital mortality was assessed through multivariable logistic regression and competing risk analyses. Results: Out of 1401 patients admitted at the participating centres with confirmed diagnosis of COVID‐19, 226 (16.1%) underwent transthoracic echocardiography (TTE) and were included in the present analysis. In‐hospital death occurred in 68 patients (30.1%). At multivariable analysis, left ventricular ejection fraction (LVEF, P <.001), tricuspid annular plane systolic excursion (TAPSE, P <.001) and ARDS (P <.001) were independently associated with in‐hospital mortality. At competing risk analysis, we found a significantly higher risk of mortality in patients with ARDS vs those without ARDS (HR: 7.66; CI: 3.95‐14.8), in patients with TAPSE ≤17 mm vs those with TAPSE >17 mm (HR: 5.08; CI: 3.15‐8.19) and in patients with LVEF ≤50% vs those with LVEF >50% (HR: 4.06; CI: 2.50‐6.59). Conclusions: TTE might be a useful tool in risk stratification of patients with COVID‐19. In particular, reduced LVEF and reduced TAPSE may help to identify patients at higher risk of death during hospitalization. [ABSTRACT FROM AUTHOR]

The dynamic response of a vehicle–bridge interaction (VBI) system is a noisy, nonstationary, and multicomponent response with closely spaced spectral components. Considering the ultimate goal as utilizing the VBI system instantaneous frequencies (IFs) for bridge condition monitoring, this paper carries out a systematic study to investigate the performance of four advanced time‐frequency analysis techniques on a series of VBI responses: Hilbert–Huang transformation (HHT), continuous wavelet transform (CWT), robust local mean decomposition (robust‐LMD), and wavelet synchrosqueezed transform (WSST). The novel contribution of this study is the application of the two latter techniques. The synthesized tests demonstrate that the WSST is the best method to precisely separate and localize in time the closely spaced resonances. Therefore, the WSST is applied to field measurements obtained from the Boyne viaduct in Ireland, as well. The results verify the capacity of this method to deal with time‐varying vibrations adequately. [ABSTRACT FROM AUTHOR]

An integrated approach that combines geophysical surveys and numerical simulations is proposed to study the processes that govern the fluid flow along active fault zones. It is based on the reconstruction of the architecture of the investigated fault system, as well as the identification of possible paths for fluid migration, according to the distribution of geophysical parameters retrieved by multi-methodological geophysical prospecting. The aim is to establish, thanks to constraints deriving from different types of data (e.g., geological, geochemical and/or hydrogeological data), an accurate 3D petrophysical model of the survey area to be used for simulating, by numerical modelling, the physical processes likely taking place in the imaged system and its temporal evolution. The effectiveness of the proposed approach is tested in an active fault zone in the Matese Mts (southern Italy), where recent, accurate geochemical measurements have registered very high anomalous values of non-volcanic natural emissions of CO2. In particular, a multi-methodological geophysical survey, consisting of electrical resistivity tomography, self-potential and passive seismic measurements, integrated with geological data, was chosen to define the 3D petrophysical model of the investigated system and to identify possible source geometries. Three different scenarios were assumed corresponding to three different CO2 source models. The one that hypothesizes a source located along the fault plane at the depth of the carbonate basement was found to be the best candidate to represent the test site. Indeed, the performed numerical simulations provide CO2 flow estimates comparable with the values observed in the investigated area. These findings are promising for gas hazards, as they suggest that numerical simulations of different CO2 degassing scenarios could forecast possible critical variations in the amount of CO2 emitted near the fault. [ABSTRACT FROM AUTHOR]

Growing evidence has unveiled the pathological significance of Tau in many cancers, including the most aggressive and lethal brain tumor glioblastoma multiform (GBM). In this regard, we have recently examined the structure–activity relationship of a new series of seventeen 2-aminothiazole-fused to flavonoid hybrid compounds (TZF) on Tau-overexpressing GBM cells. Here, we evaluated the anticancer activities of the two lead compounds 2 and 9 using multi-cellular spheroids (MCSs) which represent an easy 3D human cell model to mimic GBM organization, physical constraints and drug penetration. The two compounds reduced cell evasion from spheroids up to three times, especially for Tau-expressing cells. As a first step towards a therapeutic approach, we quantified the effects of these compounds on MCS growth using two complementary protocols: single and repeated treatments. A single injection with compound 9 slowed down the growth of MCSs formed with U87 shCTRL cells by 40% at 10 µM. More interestingly, multiple treatment with compound 9 slowed the growth of U87 shCTRL spheroids by 40% at a concentration of 5 µM, supporting the increased bioavailability of compound 9 within MCSs. In conclusion, compound 9 deserves particular attention as promising candidate for specifically targeting Tau-expressing cancers such as GBM. [ABSTRACT FROM AUTHOR]

Context. Stellar activity is comprised of various phenomena, mainly spots and faculae. It is one of the main sources of noise in exoplanetary observations because it affects both spectroscopic and photometric observations. In studying young active planetary systems, we need to model the activity of the host stars to remove astrophysical noise from our observational data. Aims. We model the contribution of stellar spots in photometric observations. Through the use of multi-band photometry, we aim to extract the geometric properties of the spots and constrain their temperatures. Methods. We analysed multi-band photometric observations acquired with the 80 cm Marcon telescope of the Osservatorio Polifunzionale del Chianti of V1298 Tau, assuming the photometric modulation observed in different bands is attributed to cold spots. Results We constrained the effective temperature of the active regions present on the surface of V1298 Tau, resulting from a combination of spots and faculae. We tested our hypothesis on solar data, verifying that we successfully measured the size of the dominant active region and its averaged effective temperature. [ABSTRACT FROM AUTHOR]

Aim: To assess the chemical and microstructural characteristics of dentine after the use of two irrigation protocols and correlate this with the antimicrobial properties of hydraulic calcium silicate cement (HCSC) sealers and changes to the dentine structure/chemistry after sealer placement. Methodology: Two irrigation protocols – Protocol A using 2% NaOCl used 5 mL/5 min and Protocol B with 2% NaOCl (5 mL/5 min) followed by 17% EDTA (5 mL/3 min) – were used to prepare dentine. The chemical and microstructural changes following irrigation were assessed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and Fourier transform infrared (FT‐IR) spectroscopy (n = 5) on dentine obtained from the mid‐root and coronal parts of extracted human teeth. Four sealers (AH Plus, BioRoot, MTA Fillapex, TotalFill) were characterized by SEM/EDS (n = 3). The ability of the sealers to eradicate intratubular Enterococcus faecalis biofilms was assessed by live/dead dye and confocal laser scanning microscopy to measure the percentage of living cells. The effect of combined irrigation and root filling on dentine was assessed by SEM and EDS analysis (n = 5). Statistical analysis was undertaken using one‐way anova and a number of post hoc tests to detect intergroup differences. The F‐test was used for comparison of variances in the microbiology testing. Results: The use of NaOCl alone left the smear layer intact, with traces of chlorine remaining on dentine. The use of BioRoot sealer restored the calcium levels of dentine which had been depleted by the irrigation with EDTA. BioRoot exhibited antimicrobial properties against intratubular bacteria even in the presence of smear layer (Protocol A). Smear layer removal improved the bactericidal effect of all sealers and Ca2+ leaching. The use of a chelating agent was important for the intratubular sealer penetration for AH Plus but not the other sealers. Conclusion: The removal of smear layer was necessary for penetration of AH Plus into the dentinal tubules. BioRoot was a more effective sealer in reducing the bacterial load in the dentinal tubules than the other materials tested and the presence of smear layer did not affect its activity. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to investigate the role of resistance‐associated substitutions (RASs) to direct‐acting‐antivirals (DAAs) in HCV genotype 3 (GT3). Methods: Within the Italian VIRONET‐C network, a total of 539 GT3‐infected patients (417 DAA‐naïve and 135 DAA‐failures, of them, 13 at both baseline and failure) were analysed. Sanger sequencing of NS3/NS5A/NS5B was performed following home‐made protocols. Results: The majority of patients were male (79.4%), 91.4% were injection drug users, 49.3% were cirrhotic and 13.9% were HIV co‐infected. Phylogenetic analysis classified sequences as GT3a‐b‐g‐h (98%‐0.4%‐0.2%‐1.2%) respectively. Overall, 135 patients failed a DAA regimen: sofosbuvir (SOF)/daclatasvir (DCV) or velpatasvir (VEL)±ribavirin (RBV) (N = 91/15) and glecaprevir (G)/pibrentasvir (P) (N = 9). Moreover, 14.8% of patients were treated with suboptimal regimens for GT3: 3D ± RBV (Paritaprevir/r + Ombitasvir+Dasabuvir, N = 15), SOF + Simeprevir (SIM) (N = 1) or SOF/Ledipasvir (LDV) ± RBV (N = 4). RAS prevalence was 15.8% in DAA‐naïve patients. At failure, 81.5% patients showed at least one RAS: 11/25 (44.0%) in NS3, 109/135 (80.7%) in NS5A, 7/111 (6.3%) in NS5B SOF‐failures. In NS5A‐failures, Y93H RAS was the most prevalent (68.5% vs 5.1% DAA‐naïve, P <.001) followed by A30K (12.7% vs 2.8% in DAA‐naïve, P <.001). Analysing baseline samples, a higher prevalence of NS5A‐RASs was observed before treatment in DAA‐failures (5/13, 38.5%) vs DAA‐naïves (61/393, 15.5%, P =.04). Regarding 228 DAA‐naïve patients with an available outcome, 93.9% achieved a SVR. Interestingly, patients with baseline Y93H and/or A30K had SVR rate of 72.2% vs 95.7% for patients without NS5A‐RASs (P =.002). Conclusions: In this real‐life GT3 cohort, the majority of failures harboured resistant variants carrying NS5A‐RASs, the most frequent being Y93H. The presence of natural NS5A‐RASs before treatment was associated with failure. Further analyses are needed to confirm this observation, particularly for the new current regimens. [ABSTRACT FROM AUTHOR]

This paper presents a technique for rapid diagnostics of structural integrity that exploits spectral sidebands measured by the continuous scanning LDV (CSLDV) measurement method. Structural integrity can be monitored by Operational Deflection Shapes ODSs, which can be quickly measurable at any excitation frequency when a laser continuously scans a vibrating surface. The LDV output time series is an amplitude modulated signal, and its spectral lines are used for recovering polynomial coefficients which build a polynomial function describing a deflection shape. The process of conversion from the time series to a polynomial function can be biased by measurement and analysis uncertainty which eventually will affect the quality of recovered ODS. This paper will show that an effective, rapid and straightforward diagnostics can be yielded by direct analysis of the spectral sidebands without the need to be transformed into polynomial coefficients. The Relative Amplitude of the Sidebands to the Total Amplitude Reference (RASTAR) method is an indicator that exploits the relative amplitude of the sidebands against a datum reference. The relative magnitudes of the sidebands will not change in the absence of any the structural change, and it is independent of the vibration response amplitudes set for the measurements. Such diagnostic method suits maintenance operations of structures which could be quickly scanned by an SLDV system providing an indicative level of structural integrity over the number of duty cycles. [ABSTRACT FROM AUTHOR]

As part of the activities performed by the DEMO Central Team (DCT) to study alternative configurations of the Water-Cooled Lead Lithium (WCLL) Breeding Blanket (BB), to overcome the open issues that emerged at the end of the Pre-Conceptual Design phase, a new concept, the WCLL BB "double bundle" (db), was developed. This concept adopts an array of db tubes poloidally distributed inside the breeding zone, mimicking the arrangement inside heat exchangers. These are coaxial pipes the gap between which is filled with PbBi (or alternatively with gas and fins), which avoids direct contact between PbLi and water in case of in-box LOCA events. Similarly, the First Wall channel cooling water is separated from the PbLi. The use of PbBi as an inert fluid makes the Segment Box (SB) sizing less stringent: in the case of an in-box LOCA due to a break of the water cooling circuit inside the BB SB, the pressurized volume is only the PbBi one, instead of the whole SB volume as in the reference WCLL design configuration. Consequently, the total amount of steel inside the BB can be reduced, with benefits in terms of increased tritium breeding ratio. Within this framework, University of Palermo, in support of the DCT and under the EUROfusion action, preliminarily analysed the steady-state thermal, thermo-hydraulic and normal and off-normal thermo-mechanical performances of this concept, following a theoretical-numerical approach based on finite volume and finite element methods, and adopting the ANSYS CFX and ANSYS Mechanical codes. The analyses carried out allowed a preliminary optimization of the design, improving the thermal and thermo-mechanical performances of the WCLL-db BB, in compliance with the design requirements, while reducing the total steel amount. Models, assumptions and main results are herewith reported and critically discussed. [ABSTRACT FROM AUTHOR]

• Data Adequacy (DA) is aimed at controlling the impact of user effect on Thermal-Hydraulics (T_H) code results. • A Multi Criteria Decision Making (MCDM) approach is proposed to overcome the expert judgement on DA assessment. • The approach is exemplified on experimental databases made available to the participants of the ATRIUM project. • The reliance on subjective expert-based evaluations is reduced and uncertainties are properly quantified. Data Adequacy (DA) assessment of experimental databases must be performed to control the impact of user effects on the results provided by the Thermal-Hydraulic (T-H) codes employed for the safety assessment of Nuclear Power Plants (NPPs). The activity is typically based on expert judgement, which, however, lacks a rigorous treatment of the uncertainties. With the objective to overcome this limitation, we propose a Multi-Criteria Decision Making (MCDM) approach to consider the Representativeness (R) and Completeness (C) of the databases by an Analytic Hierarchy Process (AHP) combined with Interval Analysis (IA) and Monte Carlo Simulation (MCS) to quantify the uncertainty. The approach for DA is exemplified on the databases made available to the participants of the ATRIUM (Application Tests for Realization of Inverse Uncertainty quantification and validation Methodologies in thermal hydraulics) project promoted by the WGAMA of the OECD-NEA, whose ultimate objective is the systematic application of Inverse Uncertainty Quantification (IUQ) methodologies to assess the uncertainties affecting the T-H model of an Intermediate Break Loss Of Coolant Accident (IBLOCA) of a Light Water Reactor (LWR). The outcomes of the application show that the proposed approach allows overcoming some of the limitations of expert-based approaches, reducing the reliance on subjective evaluations through the incorporation of quantitative metrics in the analysis and via the proper quantification of the uncertainty. [ABSTRACT FROM AUTHOR]

Objectives: To describe and estimate the frequency of pregnancy outcomes, clinical and laboratory characteristics of vertical transmission of CHIKV in the neonate. Study design: We performed a systematic review evaluating the clinical presentation of perinatally-acquired CHIKV infection in neonates. The search was performed using Medline (via PubMed), LILACS, Web of Science, Scielo, Google Scholar and Open grey to identify studies assessing vertical transmission of CHIKV up to November 3, 2020. There were no search restrictions regarding the study type, the publication date or language. Studies with no documented evidence of CHIKV infection in neonates (negative RT-PCR or absence of IgM) were excluded. Results: From the 227 studies initially identified, 42 were selected as follows: 28 case reports, 7 case series, 2 cross-sectional studies and 5 cohort studies, for a total of 266 CHIKV infected neonates confirmed by serological and/or molecular tests. The vertical transmission rate was 50% in the Reunion Island outbreak, which was the subject of the majority of the studies; the premature delivery were reported in 19 (45.2%) studies; the rate of fetal distress was 19.6% of infected babies and fetal loss occurred in 2% of the cases. Approximately 68.7% of newborns were diagnosed with encephalopathy or encephalitis after perinatally acquired CHIKV. Most of the infected neonates were born healthy, developing CHIKV sepsis clinical syndrome within the first week of life. Conclusions: We alert neonatologists to the late manifestations of neonatal CHIKV infection, relevant to the management and reduction of morbidity. A limitation of our review was that it was not possible to carry out meta-analysis due to differences in study design and the small number of participants. [ABSTRACT FROM AUTHOR]

There are limited data on patients with chronic HCV infection in whom combination voxilaprevir (VOX), velpatasvir (VEL), sofosbuvir (SOF) retreatment fails. Thus, we aimed to assess treatment failure and rescue treatment options in these patients. Samples from 40 patients with HCV genotypes (GT) 1-4 in whom VOX/VEL/SOF retreatment failed were collected within the European Resistance Study Group. Population-based resistance analyses were conducted and clinical parameters and retreatment efficacies were evaluated retrospectively in 22 patients. Most VOX/VEL/SOF failure patients were infected with HCV GT3a (n = 18, 45%) or GT1a (n = 11, 28%) and had cirrhosis (n = 28, 70%). Previous treatments included an NS3-inhibitor (30%), an NS5A-inhibitor (100%) and SOF (85%). Baseline RAS data from a subgroup of patients before VOX/VEL/SOF retreatment (78%) showed few NS3 RASs apart from Q80K in GT1a (40%), typical NS5A RAS patterns in most patients (74%) and no S282T in NS5B. Sequencing after VOX/VEL/SOF failure was available in 98% of patients and showed only minor changes for NS3 and NS5A RASs. In 22 patients, rescue treatment was initiated with glecaprevir, pibrentasvir alone (n = 2) or with SOF±ribavirin (n = 15), VOX/VEL/SOF±ribavirin (n = 4) or VEL/SOF and ribavirin (n = 1) for 12 to 24 weeks. Sustained virologic response was achieved in 17/21 (81%) patients with a final treatment outcome. Of these, 2 GT3a-infected patients had virologic failure after rescue treatment with VEL/SOF or glecaprevir/pibrentasvir+SOF+ribavirin, and 2 patients with cirrhosis died during treatment or before reaching SVR12. VOX/VEL/SOF failure was mainly observed in HCV GT3- and GT1a-infected patients with cirrhosis and was not associated with specific RAS patterns within NS3, NS5A or NS5B target regions. Rescue treatment with multiple targeted therapies was effective in most patients. The advent of direct-acting antivirals has enabled the effective cure of chronic hepatitis C in most patients. However, treatment failure occurs in some patients, who are often retreated with a combination regimen called VOX/VEL/SOF, which is associated with very high rates of cure. However, VOX/VEL/SOF retreatment also fails in some patients. Herein, we analysed samples from patients in whom VOX/VEL/SOF retreatment failed and we assessed the efficacy of different rescue therapies, showing that rescue treatment is effective in most patients (81%). [Display omitted] • In patients with VOX/VEL/SOF failure HCV GT3a infections and cirrhosis were overrepresented and HCC was present in 28% of patients • Sequencing after VOX/VEL/SOF failure showed minor changes in the NS3 and NS5A RAS pattern and no NS5B RASs were observed in comparison to baseline • Rescue treatment was conducted in 55% of patients and the main reasons were the presence of advanced liver disease and/or liver cancer • The majority of patients (68%) received G/P+SOF ± ribavirin • Rescue treatment was effective in the majority of patients with 81% SVR [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the retinal and choriocapillaris vascular networks in macular region and the central choroidal thickness (CCT) in patients affected by Huntington disease (HD), using optical coherence tomography angiography (OCTA) and enhanced depth imaging spectral-domain OCT (EDI SD-OCT).Methods: We assessed the vessel density (VD) in superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) using OCTA, while CCT was measured by EDI SD-OCT.Results: Sixteen HD patients (32 eyes) and thirteen healthy controls (26 eyes) were enrolled in this prospective study. No significant difference in retinal and choriocapillaris VD was found between HD patients and controls while CCT turned to be thinner in patients respect to controls. There were no significant relationships between OCTA findings and neurological parameters.Conclusion: The changes in choroidal structure provide useful information regarding the possible neurovascular involvement in the physiopathology of HD. Choroidal vascular network could be a useful parameter to evaluate the vascular impairment that occurs in this neurodegenerative disease. [ABSTRACT FROM AUTHOR]

I really appreciate the article by the National Comprehensive Cancer Network ePRO Workgroup, by Cracchiolo and colleagues who have proposed 10 guiding principles for the implementation of electronic patient-reported outcomes (ePROs) in the clinical management of patients with cancer.[1] Among the principles related to the collection of ePROs, the authors dedicate the fifth principle to the selection of patients who should routinely receive ePROs. Which patients should receive electronic patient-reported outcome measures in clinical practice? Importantly, this recommendation applies to both patients with advanced disease being treated with palliative intent and patients receiving systemic treatment within a strategy with potentially curative intent. [Extracted from the article]