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Professional Growth Plans (PGPs), a model of professional development for educators, were completed in the context of Professional Learning Communities (PLCs) as part of a grant from a state Professional Educator Standards Board. Participants were in the Pacific Northwest of the United States and represented different educator roles in two urban elementary schools. The PGP process was introduced in PLCs and focused on the implementation of High Leverage Practices (HLPs) for inclusive classrooms (McLeskey et al., 2019). In a collaborative effort with university facilitators, educators engaged in tenets of Participatory Action Research (PAR) through the enactment of the PGP process to implement and reflect on outcomes related to their use of HLPs. Educators selected PGP goals focused on areas of instructional growth and improvement of student performance. PAR was enacted in the context of educators' individual instructional settings through the implementation of PGPs. The purpose of the grant was to familiarize and support educators in the PGP process. The purpose of the study was to identify educators' perceived benefits and challenges with the implementation of PGPs within the context of a collaborative PLC. Educators indicated that collaboration with educators across roles, including university partners, and the structure of the PGP process within the context of a PLC positively influenced their professional growth and student outcomes.

Abstract Optical materials play a key role in enabling modern optoelectronic technologies in a wide variety of domains such as the medical or the energy sector. Among them, nonlinear optical crystals are of primary importance to achieve a broader range of electromagnetic waves in the devices. However, numerous and contradicting requirements significantly limit the discovery of new potential candidates, which, in turn, hinders the technological development. In the present work, the static nonlinear susceptibility and dielectric tensor are computed via density-functional perturbation theory for a set of 579 inorganic semiconductors. The computational methodology is discussed and the provided database is described with respect to both its data distribution and its format. Several comparisons with both experimental and ab initio results from literature allow to confirm the reliability of our data. The aim of this work is to provide a relevant dataset to foster the identification of promising nonlinear optical crystals in order to motivate their subsequent experimental investigation.

A total of 209 events of quasi-monochromatic atmospheric gravity waves (QMGWs) were acquired over 5 years of gravity waves (GWs) observation in southern Brazil. The observations were made by measuring the OH (hydroxyl radical) emission using an all-sky imager hosted by the Southern Space Observatory (SSO) coordinated by the National Institute for Space Research at São Martinho da Serra (RS) (29.44° S, 53.82° W). Using a two-dimensional fast-Fourier-Transform-based spectral analysis, it has been shown that the QMGWs have horizontal wavelengths of 10–55 km, periods of 5–74 min, and phase speeds up to 100 m s−1. The waves exhibited clear seasonal dependence on the propagation direction with anisotropic behavior, propagating mainly toward the southeast during the summer and autumn seasons and mainly toward the northwest during the winter. On the other hand, the propagation directions in the spring season exhibited a wide range from northwest to south. A complementary backward ray-tracing result revealed that the significant factors contributing to the propagation direction of the QMGWs are their source locations and the dynamics of the background winds per season. Three case studies in winter were selected to investigate further the propagation dynamics of the waves and determine their possible source location. We found that the jet stream associated with the cold front and their interaction generated these three GW events.

Abstract Background Circulating cell-free DNA (cfDNA, liquid biopsy) is a powerful tool to detect molecular alterations. However, depending on tumor characteristics, biology and anatomic localization, cfDNA detection and analysis may be challenging. Gliomas are enclosed into an anatomic sanctuary, which obstacles the release of cfDNA into the peripheral blood. Therefore, the advantages of using liquid biopsy for brain tumors is still to be confirmed. The present study evaluates the ability of liquid biopsy to detect IDH1 mutations and its correlation with survival and clinical characteristics of glioma patients. Methods Blood samples obtained from glioma patients were collected after surgery prior to the adjuvant therapy. cfDNA was extracted from plasma and IDH1 p.R132H mutation analysis was performed on a digital droplet PCR. χ2-test and Cohen k were used to assess the correlation between plasma and tissue IDH1 status, while Kaplan Meier curve and Cox regression analysis were applied to survival analysis. Statistical calculations were performed by MedCalc and GraphPad Prism software. Results A total of 67 samples were collected. A concordance between IDH1 status in tissue and in plasma was found (p = 0.0024), and the presence of the IDH1 mutation both in tissue (138.8 months vs 24.4, p

Lorenzo Viselli,1,* Fabiana Festucci,1,* Maria Chiara Pino,1 Aurora D’Atri,1 Federico Salfi,1 Giulia Amicucci,1,2 Domenico Corigliano,1,2 Federica Naccarato,1 Michele Ferrara,1 Daniela Tempesta1 1Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 2Department of Psychology, Sapienza University of Rome, Rome, Italy*These authors contributed equally to this workCorrespondence: Michele Ferrara, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy, Email michele.ferrara@univaq.itPurpose: The present study aimed to validate the Italian version of the Iowa Resistance to Sleeplessness Test (iREST), a 16-item self-report assessing resilience to sleep debt in the affective, cognitive, and somatic domains.Participants and Methods: We examined its factor structure, assessed internal consistency and criterion validity, and established test-retest reliability on 768 Italian native speakers (65.8% of women) with a mean age of 25.98 years old.Results: Confirmatory factor analysis (CFA) revealed a new 13-item structure for the Italian iREST (iREST-13), demonstrating more satisfactory goodness-of-fit values, and exhibiting good internal consistency (Cronbach’s α ranging from 0.73 to 0.89), relative to the 16-item original version. Results supported the iREST convergent validity, showing significant independence from established measures of sleep; low correlations with conceptually unrelated measures supported divergent validity, indicating that the iREST effectively measures resistance to sleeplessness without confounding with other constructs. Lastly, test-retest reliability was evaluated by administering the iREST to the same sample with a 2-week interval: the significant correlations supported its temporal stability.Conclusion: Further studies are needed to evaluate the applicability of the iREST in diverse populations and explore its relationship with objective sleep measures. Nevertheless, the Italian iREST provides a valuable tool for assessing resistance to sleep loss, offering insights into individual differences in resilience. Additionally, the iREST can assist in identifying individuals who require interventions to enhance resilience to sleep debt, as well as help clinicians evaluate the impact of chronic sleep disruption and deliver targeted interventions.Keywords: sleeplessness, resilience, sleep loss, vulnerability, individual differences, Italian validation

This article argues for a gradient approach to word order, which treats word order preferences, both within and across languages, as a continuous variable. Word order variability should be regarded as a basic assumption, rather than as something exceptional. Although this approach follows naturally from the emergentist usage-based view of language, we argue that it can be beneficial for all frameworks and linguistic domains, including language acquisition, processing, typology, language contact, language evolution and change, and formal approaches. Gradient approaches have been very fruitful in some domains, such as language processing, but their potential is not fully realized yet. This may be due to practical reasons. We discuss the most pressing methodological challenges in corpus-based and experimental research of word order and propose some practical solutions.

This essay combines the notions of creative paratopy and discursive ethos in order to shed light on aspects of the work of Benjamin Fondane, a Jewish writer of Romanian origin who chose French as his language of writing. Le Mal des fantômes, a collection of poems written in his adopted language, integrates the various dimensions of creative paratopy : in addition to the paratopy of identity, which in some cases becomes “maximal”, there is a spatial paratopy, a temporal paratopy and a linguistic paratopy. The analysis focuses on his poem Ulysse, which representatively includes most of his typologies, and shows that this unstable and erratic “localisation” is involved in the emergence of a “physicality” and a “character” which belong to a specific “ethical world” and point to “a dynamic of positioning” which is spread over several planes at the same time.

Purpose: Clinical evidence suggests an association between comorbidities and outcome in patients with glioblastoma (GBM). We hypothesised that the internal carotid artery (ICA) calcium score could represent a promising prognostic biomarker in a competing risk analysis in patients diagnosed with GBM. Methods: We validated the use of the ICA calcium score as a surrogate marker of the coronary calcium score in 32 patients with lung cancer. Subsequently, we assessed the impact of the ICA calcium score on overall survival in GBM patients treated with radio-chemotherapy. Results: We analysed 50 GBM patients. At the univariate analysis, methyl-guanine-methyltransferase gene (MGMT) promoter methylation (p = 0.048), gross total tumour resection (p = 0.017), and calcium score (p = 0.011) were significant prognostic predictors in patients with GBM. These three variables also maintained statistical significance in the multivariate analysis. Conclusions: the ICA calcium score could be a promising prognostic biomarker in GBM patients.

Abstract The COVID-19 global pandemic has changed considerably the way time-sensitive disorders are treated. Home isolation, people’s fear of contracting the virus and hospital reorganisation have led to a significant decrease in contacts between citizens and the healthcare system, with an expected decrease in calls to the Emergency Medical Services (EMS) of the Friuli-Venezia Giulia (FVG) region. However, mortality in clinical emergencies like acute ST-elevation myocardial infarction (STEMI), stroke and out-of-hospital cardiopulmonary arrest (OHCA) remained high. An observational retrospective cross-sectional study was carried out in FVG, taking into account the period between March 1, 2020, and May 31, 2020, the first wave of the COVID-19 pandemic, and comparing it with the same period in 2019. The flow of calls to the EMS was analysed and COVID-19 impact on time-sensitive disorders (STEMIs, ischemic strokes and OHCPAs) was measured in terms of hospitalisation, treatment and mortality. Despite a −8.01% decrease (p value ˂0.001) in emergency response, a 10.89% increase in calls to the EMS was observed. A lower number of advanced cardiopulmonary resuscitations (CPR) (75.8 vs 45.2%, p=0.000021 in April) and ROSC (39.1 vs 11.6%, p=0.0001 in April) was remarked, and survival rate dropped from 8.5 to 5%. There were less strokes (−27.5%, p value=0.002) despite a more severe onset of symptoms at hospitalisation with NHISS˃10 in 38.47% of cases. Acute myocardial infarctions decreased as well (−20%, p value=0.05), but statistical significances were not determined in the variables considered and in mortality. Despite a lower number of emergency responses, the number of calls to the EMS was considerably higher. The number of cardiac arrests treated with advanced CPR (ALS) was lower, but mortality was higher. The number of strokes decreased as well, but at the time of hospitalisation the clinical picture of the patient was more severe, thus affecting the outcome when the patient was discharged. Finally, STEMI patients decreased; however, no critical issues were observed in the variables taken into account, neither in terms of response times nor in terms of treatment times.

The studies on the sources of three concentric gravity waves (CGWs) excited by a moving mesoscale convective system (MCS) on the night of 1–2 October 2019 are investigated. These CGWs were observed using a hydroxyl (OH) all-sky imager, whereas the MCS was observed by the Geostationary Operational Environmental Satellite (GOES). Using 2D spectral analysis, we observed that the three CGWs have horizontal wavelength λH between ∼30–55 km, phase speed cH∼70–90 m s−1, and period τ∼7–12 min. Using backward ray tracing, we found that two of the CGWs were excited from convective cores within the MCS. We also found that the epicenters of the two waves were close to the tropopause positions of the ray-traced paths and nearby convective cores. Regarding the source, we verified that on this night the tropopause was ∼-80 ∘C, which was ∼10 ∘C colder than the days preceding and after the MCS and also colder than usually observed. Since the tropopause height and temperature are fundamental parameters underlying the analysis of the overshooting extent, we developed our own methodology to establish a reference tropopause that would enable a quantitative estimate of this parameter. Since the MCS (CGWs source) was moving, the overshooting convective cores were tracked in space and time. Using the tracking of the overshooting tops (OTs) in space and time with the aid of reverse ray tracing, we found that two out of the three CGWs were excited by the MCS, whereas the source of the remaining one was not directly associated with the MCS.

Implication Statement We developed a pharmacist-led one-month teaching rotation for medical residents to learn HIV pharmacotherapy. This interprofessional education (IPE) was deemed extremely valuable by postgraduate-year-3 residents who intended to have a future practice in HIV care. The overarching concept of this rotation was for the medical trainee to “become-the-pharmacist”, learning to recognize, prevent, and manage drug-related issues in HIV patients. Pharmacist-led IPE should be considered to support medical training in other highly specialized pharmacotherapeutic areas.

Cerebral venous thrombosis (CVT) is a rare cause of stroke, particularly in young adults. Several known thrombophilic conditions may lead to an increased CVT risk. Interestingly, few cases in the literature have reported an association between CVT and thyrotoxicosis. Here, we describe the case of a young woman with CVT and concomitant thyrotoxicosis, without any other known prothrombotic conditions. We also performed a literature review of CVT cases and hyperthyroidism, searching for all articles published in peer-reviewed journals. We identified 39 case reports/case series concerning patients with CVT associated with thyrotoxicosis, highlighting, in most cases, the association with additional known prothrombotic factors. We then discussed the possible mechanisms by which hyperthyroidism could underlie a pro-coagulative state resulting in CVT. Thyroid disease might be a more common prothrombotic risk factor than expected in determining CVT. However, in most cases, a coexistence of multiple risk factors was observed, suggesting a multifactorial genesis of the disorder. We hope that this work may alert clinicians to consider thyrotoxicosis as a potential risk factor for CVT, even in patients who apparently have no other pro-coagulative conditions.

Mercury (Hg) fate and transport research requires more effort to obtain a deep knowledge of its biogeochemical cycle, particularly in the Southern Hemisphere and Tropics that are still missing of distributed monitoring sites.Continuous monitoring of atmospheric Hg concentrations and trend worldwide is relevant for the effectiveness evaluation of the Minamata Convention on Mercury (MCM) actions. In this context, Gaseous Elemental Mercury (GEM) and total mercury (THg) in precipitations were monitored from 2013 to 2019 at the Amsterdam Island Observatory (AMS - 37°48′S, 77°34′E) to provide insights into the Hg pathway in the remote southern Indian Ocean, also considering ancillary dataset of Rn-222, CO2, CO, and CH4. GEM average concentration was 1.06 ± 0.07 ng m−3, with a slight increase during the austral winter due to both higher wind speed over the surface ocean and contributions from southern Africa. In wet depositions, THg average concentration was 2.39 ± 1.17 ng L−1, whereas the annual flux averaged 2.04 ± 0.80 μg m−2 year−1. In general, both GEM and Volume-Weighted Mean Concentration (VWMC) of THg did not show an increasing/decreasing trend over the seven-year period, suggesting a substantial lack of evolution about emission of Hg reaching AMS.Air masses Cluster Analysis and Potential Source Contribution Function showed that oceanic evasion was the main Hg contributor at AMS, while further contributions were attributable to long-range transport events from southern Africa, particularly when the occurrence of El Niño increased the frequency of wildfires.

Abstract Background Approximately one third of cancer patients will develop spinal metastases, that can be associated with back pain, neurological symptoms and deterioration in performance status. Stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT) have been offered in clinical practice mainly for the management of oligometastatic and oligoprogressive patients, allowing the prescription of high total dose delivered in one or few sessions to small target volumes, minimizing the dose exposure of normal tissues. Due to the high delivered doses and the proximity of critical organs at risk (OAR) such as the spinal cord, the correct definition of the treatment volume becomes even more important in SBRT treatment, thus making it necessary to standardize the method of target definition and contouring, through the adoption of specific guidelines and specific automatic contouring tools. An automatic target contouring system for spine SBRT is useful to reduce inter-observer differences in target definition. In this study, an automatic contouring tool was evaluated. Methods Simulation CT scans and MRI data of 20 patients with spinal metastases were evaluated. To evaluate the advantage of the automatic target contouring tool (Elements SmartBrush Spine), which uses the identification of different densities within the target vertebra, we evaluated the agreement of the contours of 20 spinal target (2 cervical, 9 dorsal and 9 lumbar column), outlined by three independent observers using the automatic tool compared to the contours obtained manually, and measured by DICE similarity coefficient. Results The agreement of GTV contours outlined by independent operators was superior with the use of the automatic contour tool compared to manually outlined contours (mean DICE coefficient 0.75 vs 0.57, p = 0.048). Conclusions The dedicated contouring tool allows greater precision and reduction of inter-observer differences in the delineation of the target in SBRT spines. Thus, the evaluated system could be useful in the setting of spinal SBRT to reduce uncertainties of contouring increasing the level of precision on target delivered doses.

Background: Student-run health initiatives in the community setting have been utilized to provide practical experience for undergraduate students to develop professional competencies, gain exposure to diverse populations, and to engage in activities of social accountability. There is much literature on student-run health initiatives; however, there is no consensus on a definition of this concept or a comprehensive synthesis of the literature that describes student-run health initiatives offered by students in pre-licensure healthcare education programs. Purpose: To provide a concept analysis of, and propose a definition for, student-run health initiatives that provide community-based services for students during pre-licensure health discipline education. Methods: A systematic literature search and review process was used to identify and synthesize peer-reviewed articles from 7 academic databases covering a range of pre-licensure health disciplines and education. Walker and Avant’s framework for concept analysis was used to guide exploration of attributes, antecedents and consequences of student-run initiatives, and to inform development of a definition for this concept. Results: The review yielded 222 articles for data extraction and represented 17 distinct pre-licensure health disciplines, 18 health-related disciplines, and a range of other baccalaureate and graduate programs. Our analysis revealed 16 definitions, 5 attributes, 6 antecedents, and consequences identified for student-run health initiatives. Attributes were Provision of Service, Service is Free, Target Clientele, Volunteerism, and Student Governance. Antecedents included Purpose/Rationale, Affiliation with Academic Unit, Location and Partnerships, Funding and Resources, Professional Oversight, and Preparation for Student Role. Consequences were improved access to services and outcomes for clients; competency development, personal gains and interprofessional learning for students; and positive outcomes for broader systems, such as decrease of service utilization and cost/benefit. Conclusions: There was no clear conceptual definition for student-run health initiatives, but many defining characteristics and well-described exemplars in the literature. Given the variations in purpose and scope of these initiatives, particularly to distinguish degree of students’ roles in operations and the involvement of academic institutions, we propose 3 distinct conceptual definitions: student-run, student-led, and student-infused health initiatives.

Introduction Clinical trials, although academically accepted as the most effective treatment available for cancer patients, poor accrual to clinical trials remains a significant problem. A clinical trials navigator (CTN) program was piloted where patients and/or their healthcare professionals could request a search and provide a list of potential cancer clinical trials in which a patient may be eligible based on their current status and disease. Objectives This study examined the outcomes of a pilot program to try to improve clinical trials accrual with a focus on patients at medium to small sized cancer programs. Outcomes examined included patient disposition (referral to and accrual to interventional trials), patient survival, sites of referral to the CTN program. Methods One 0.5 FTE navigator was retained. Stakeholders referred to the CTN through the Canadian Cancer Clinical Trials Network. Demographic and outcomes data were recorded. Results Between March 2019 and February 2020, 118 patients from across Canada used the program. Seven per cent of patients referred were enrolled onto treatment clinical trials. No available trial excluded 39% patients, and 28% had a decline in their health and died before they could be referred or enrolled onto a clinical trial. The median time from referral to death was 109 days in those that passed. Conclusion This novel navigator pilot has the potential to increase patient accrual to clinical trials. The CTN program services the gap in the clinical trials system, helping patients in medium and small sized cancer centres identify potential clinical trials at larger centres.

BackgroundGlioblastoma (GB) is the most severe form of brain cancer, with a 12-15 month median survival. Surgical resection, temozolomide (TMZ) treatment, and radiotherapy remain the primary therapeutic options for GB, and no new therapies have been introduced in recent years. This therapeutic standstill is primarily due to preclinical approaches that do not fully respect the complexity of GB cell biology and fail to test efficiently anti-cancer treatments. Therefore, better treatment screening approaches are needed. In this study, we have developed a novel functional precision medicine approach to test the response to anticancer treatments in organoids derived from the resected tumors of glioblastoma patients.MethodsGB organoids were grown for a short period of time to prevent any genetic and morphological evolution and divergence from the tumor of origin. We chose metabolic imaging by NAD(P)H fluorescence lifetime imaging microscopy (FLIM) to predict early and non-invasively ex-vivo anti-cancer treatment responses of GB organoids. TMZ was used as the benchmark drug to validate the approach. Whole-transcriptome and whole-exome analyses were performed to characterize tumor cases stratification.ResultsOur functional precision medicine approach was completed within one week after surgery and two groups of TMZ Responder and Non-Responder tumors were identified. FLIM-based metabolic tumor stratification was well reflected at the molecular level, confirming the validity of our approach, highlighting also new target genes associated with TMZ treatment and identifying a new 17-gene molecular signature associated with survival. The number of MGMT gene promoter methylated tumors was higher in the responsive group, as expected, however, some non-methylated tumor cases turned out to be nevertheless responsive to TMZ, suggesting that our procedure could be synergistic with the classical MGMT methylation biomarker.ConclusionsFor the first time, FLIM-based metabolic imaging was used on live glioblastoma organoids. Unlike other approaches, ex-vivo patient-tailored drug response is performed at an early stage of tumor culturing with no animal involvement and with minimal tampering with the original tumor cytoarchitecture. This functional precision medicine approach can be exploited in a range of clinical and laboratory settings to improve the clinical management of GB patients and implemented on other cancers as well.

The increasing use of agrochemicals, including fertilizers and herbicides, has led to worrying metal contamination of soils and waters and raises serious questions about the effects of their transfer to different levels of the trophic web. Accumulation and biomagnification of essential (K, Na, Mg, Zn, Ca), nonessential (Sr, Hg, Rb, Ba, Se, Cd, Cr, Pb, As), and rare earth elements (REEs) were investigated in newly emerged adults of Tenebrio molitor exposed to field-admitted concentrations of a metribuzin-based herbicide and an NPK blend fertilizer. Chemical analyses were performed using inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) supported by unsupervised pattern recognition techniques. Physiological parameters such as cuticle melanization, cellular (circulating hemocytes), and humoral (phenoloxidase enzyme activity) immune responses and mass loss were tested as exposure markers in both sexes. The results showed that NPK fertilizer application is the main cause of REE accumulation in beetles over time, besides toxic elements (Sr, Hg, Cr, Rb, Ba, Ni, Al, V, U) also present in the herbicide-treated beetles. The biomagnification of Cu and Zn suggested a high potential for food web transfer in agroecosystems. Gender differences in element concentrations suggested that males and females differ in element uptake and excretion. Differences in phenotypic traits show that exposure affects metabolic pathways involving sequestration and detoxification during the transition phase from immature-to-mature beetles, triggering a redistribution of resources between sexual maturation and immune responses. Our findings highlight the importance of setting limits for metals and REEs in herbicides and fertilizers to avoid adverse effects on species that provide ecosystem services and contribute to soil health in agroecosystems.

One of the most relevant prognostic factors in cancer staging is the presence of lymph node (LN) metastasis. Evaluating lymph nodes for the presence of metastatic cancerous cells can be a lengthy, monotonous, and error-prone process. Owing to digital pathology, artificial intelligence (AI) applied to whole slide images (WSIs) of lymph nodes can be exploited for the automatic detection of metastatic tissue. The aim of this study was to review the literature regarding the implementation of AI as a tool for the detection of metastases in LNs in WSIs. A systematic literature search was conducted in PubMed and Embase databases. Studies involving the application of AI techniques to automatically analyze LN status were included. Of 4584 retrieved articles, 23 were included. Relevant articles were labeled into three categories based upon the accuracy of AI in evaluating LNs. Published data overall indicate that the application of AI in detecting LN metastases is promising and can be proficiently employed in daily pathology practice.

Passive air samplers (PASs), which provide time-averaged concentrations of gaseous mercury over the timescale of weeks to months, are promising for filling a gap in the monitoring of atmospheric mercury worldwide. Their usefulness will depend on their ease of use and robustness under field conditions, their availability and affordability, and most notably, their ability to provide results of acceptable precision and accuracy. Here we describe a comparative evaluation of three PASs with respect to their ability to precisely and accurately record atmospheric background mercury concentrations at sites in both southern Italy and southern Ontario, Canada. The study includes the CNR-PAS with gold nanoparticles as a sorbent, developed by the Italian National Research Council, the IVL-PAS using an activated carbon-coated disk, developed by the Swedish Environmental Research Institute, and the MerPAS® using a sulfur-impregnated activated carbon sorbent, developed at the University of Toronto and commercialized by Tekran. Detection limits are deduced from the variability in the amount of mercury quantified in more than 20 field blank samples for each PAS. Analytical and sampling precision is quantified through 22 triplicate deployments for each PAS, ranging in duration from 2 to 12 weeks. Accuracy and bias are assessed through comparison with gaseous elemental mercury concentrations recorded by Tekran 2537 automated mercury analyzers operating alongside the PASs at both locations. The performance of the PASs was significantly better in Italy, with all of them providing concentrations that are not significantly different from the average concentrations of the Tekran 2537 instruments. In Canada, where weather conditions were much harsher and more variable during the February through April deployment period, there are differences amongst the PASs. At both sites, the MerPAS® is currently the most sensitive, precise, and accurate among the three PASs. A key reason for this is the larger size and the radial configuration of the MerPAS®, which results in lower blank levels relative to the sequestered amounts of mercury when compared to the other two PASs, which rely on axial diffusion geometries. Since blank correction becomes relatively smaller with longer deployments, performance tends to be closer amongst the PASs during deployments of 8 and 12 weeks.

Purpose: Adaptive stereotactic body radiation therapy (SBRT) for prostate cancer (PC) by the 1.5 T MR-linac currently requires online planning by an expert user. A fully automated and user-independent solution to adaptive planning (mCycle) of PC-SBRT was compared with user's plans for the 1.5 T MR-linac. Methods and Materials: Fifty adapted plans on daily magnetic resonance imaging scans for 10 patients with PC treated by 35 Gy (prescription dose [Dp]) in 5 fractions were reoptimized offline from scratch, both by an expert planner (manual) and by mCycle. Manual plans consisted of multicriterial optimization (MCO) of the fluence map plus manual tweaking in segmentation, whereas in mCycle plans, the objectives were sequentially optimized by MCO according to an a-priori assigned priority list. The main criteria for planning approval were a dose ≥95% of the Dp to at least 95% of the planning target volume (PTV), V33.2 (PTV) ≥ 95%, a dose less than the Dp to the hottest cubic centimeter (V35 ≤ 1 cm3) of rectum, bladder, penile bulb, and urethral planning risk volume (ie, urethra plus 3 mm isotropically), and V32 ≤ 5%, V28 ≤ 10%, and V18 ≤ 35% to the rectum. Such dose-volume metrics, plus some efficiency and deliverability metrics, were used for the comparison of mCycle versus manual plans. Results: mCycle plans improved target dose coverage, with V33.2 (PTV) passing on average (±1 SD) from 95.7% (±1.0%) for manual plans to 97.5% (±1.3%) for mCycle plans (P < .001), and rectal dose sparing, with significantly reduced V32, V28, and V18 (P ≤ .004). Although at an equivalent number of segments, mCycle plans consumed moderately more monitor units (+17%) and delivery time (+9%) (P < .001), whereas they were generally faster (–19%) in terms of optimization times (P < .019). No significant differences were found for the passing rates of locally normalized γ (3 mm, 3%) (P = .059) and γ (2 mm, 2%) (P = .432) deliverability metrics. Conclusions: In the offline setting, mCycle proved to be a trustable solution for automated planning of PC-SBRT on the 1.5 T MR-linac. mCycle integration in the online workflow will free the user from the challenging online-optimization task.

BackgroundProstate re-irradiation is an attractive treatment option in the case of local relapse after previous radiotherapy, either in the definitive or in the post-operative setting. In this scenario, the introduction of MR-linacs may represent a helpful tool to improve the accuracy and precision of the treatment.MethodsThis study reports the preliminary data of a cohort of 22 patients treated with 1.5T MR-Linacs for prostate or prostate bed re-irradiation. Toxicity was prospectively assessed and collected according to CTCAE v5.0. Survival endpoints were measured using Kaplan-Meier method.ResultsFrom October 2019 to October 2021, 22 patients received 1.5T MR-guided stereotactic body radiotherapy for prostate or prostate-bed re-irradiation. In 12 cases SBRT was delivered to the prostate, in 10 to the prostate bed. The median time to re-RT was 72 months (range, 12-1460). SBRT was delivered concurrently with ADT in 4 cases. Acute toxicity was: for GU G1 in 11/22 and G2 in 4/22; for GI G1 in 7/22, G2 in 4/22. With a median follow-up of 8 months (3-21), late G1 and G2 GU events were respectively 11/22 and 4/22. Regarding GI toxicity, G1 were 6/22, while G2 3/22. No acute/late G≥3 GI/GU events occurred. All patients are alive. The median PSA-nadir was 0.49 ng/ml (0.08-5.26 ng/ml), for 1-year BRFS and DPFS rates of 85.9%. Twenty patients remained free from ADT with 1-year ADT-free survival rates of 91.3%.ConclusionsOur experience supports the use of MR-linacs for prostate or prostate bed re-irradiation as a feasible and safe treatment option with minimal toxicity and encouraging results in terms of clinical outcomes.

Abstract Recent evidence suggests that a loss of expression of caveolin in the stromal compartment (sCav-1) of human invasive breast carcinoma (IBC) may be a predictor of disease recurrence, metastasis and poor outcome. At present, there is little knowledge regarding the expression of sCav-1 at the metastatic sites. We therefore studied sCav-1 expression in IBCs and in their axillary lymph nodes to seek a correlation with cancer metastasis. 189 consecutive invasive IBCs (53 with axillary lymph node metastases and 136 without) were studied by immunohistochemistry, using a rabbit polyclonal anti-Cav-1 antibody. In IBCs sCav-1 was evaluated in fibroblasts scattered in the tumor stroma whereas in lymph nodes sCav-1 was assessed in fibroblast-like stromal cells. For the first time, we observed a statistically significant progressive loss of sCav-1 from normal/reactive axillary lymph nodes of tumors limited to the breast to metastatic axillary lymph nodes, through normal/reactive axillary lymph nodes of tumors with axillary metastatic spread. These data indicate that Cav-1 expressed by the stromal compartment of lymph nodes, somehow, may possibly contribute to metastatic spread in IBC.

Knowledge of long-term population trends is still incomplete at the global scale. In this perspective, human and animal ecology has intensively studied the relationship between the Mean (M) size and the Variance (V) of specific attributes of subpopulations within a given regional system. One of the best-known relationships between these two attributes suitable to describe long-term population trends is governed by Taylor’s law (TL). The present article contributes to the recent literature on population trends worldwide by testing the long-term relationship (1950–2015) between the overall variance and mean in the total population of 1857 metropolitan agglomerations in 155 countries classified into 9 world macro-regions. To estimate the unknown parameter(s) of the V–M relation we made use of a simultaneous equation system using both linear (classical TL) and quadratic specifications, with the aim of ascertaining a wide range of simplified (or more complex) association rules between the two dimensions of demographic change. The empirical results show that TL is verified in all nine cases, although a quadratic relationship provides slightly better results than the classical, linear relationship. More specifically, similar estimates for both linear and quadratic relationships were characteristic of ‘new’ demographic continents with more recent and intense urbanization processes (the Americas, and African and Asian countries). The predominance of quadratic relationships characterized regions with long-established urbanization processes, such as Europe, Russia, and, partly, China and the Middle East. The relevance of the TL for a refined understanding of urbanization mechanisms worldwide, and the importance of a quadratic term for distinguishing metropolitan systems that have experienced different development paths, were finally discussed.

Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated. Moreover, the impact of other clinico-pathological features was evaluated. The number of CD4+ and CD8+ is higher in GBM tissue compared to normal brain tissue (p < 0.0001 and p = 0.0005 respectively). A positive correlation between CD4+ and CD8+ in GBM is present (rs = 0.417—p = 0.001). CD4+ TILs are inversely related to overall survival (OS) (HR = 1.79, 95% CI 1.1–3.1, p = 0.035). The presence of low CD4+ TILs combined with low CD8+ TILs is an independent predictor of longer OS (HR 0.38, 95% CI 0.18–0.79, p = 0.014). Female sex is independently related to longer OS (HR 0.42, 95% CI 0.22–0.77, p = 0.006). Adjuvant treatment, methylguanine methyltransferase (MGMT) promoter methylation, and age remain important prognostic factors but are influenced by other features. Adaptive cell-mediated immunity can affect the outcomes of GBM patients. Further studies are needed to elucidate the commitment of the CD4+ cells and the effects of different TILs subpopulations in GBM.

Substance Use Disorder (SUD) is understood as the persistent use of substances to the detriment of the individual's livelihood and wellness. SUD can have serious mental, physical, and social ramifications if not properly addressed. Though SUD can develop at any age, it is especially important to address in adolescents, given rising prevalence of certain substances (e.g. cannabis) in that age group and poor prognosis associated with early-onset SUD. Data from the National Survey on Drug Use and Health show the lifetime use of illicit drugs in people ages 12-17 is 20.9%. The same survey found the rate of Substance Use Disorder in the past year for people ages 12-17 who used illicit drugs or alcohol to be 6.3% in 2020. This paper is intended for clinicians and lay people to gain a deeper understanding of SUD in adolescents, particularly relating to alcohol, cannabis, nicotine, and opioids. Though alcohol, cannabis, and nicotine are the substances most commonly used by this age demographic nationally, opioid use – and resulting deaths – have been on the rise. According to the Centers for Disease Control and Prevention (CDC), opioids were connected to about 75% of the nearly 92,000 drug deaths in 2020. Beyond significant death rates in the general population, recent spikes in adolescent death rate tied to the synthetic opioid fentanyl – which held a relatively stable death rate from 2010 to 2019 until seeing a 94% increase from 2019 to 2020 and additional 20% increase to 2021 - warrants inquiry into opioids for this population. Each of these substances can have adverse, long-lasting effects on health if not managed properly, resulting in seriously compromised lifelong wellbeing. This article explores SUD prevalence and reviews diagnostic criteria in relation to adolescence, including a synopsis of changes in SUD classification between the DSM-IV and DSM-5 and discussion of ICD-11 and the Research Domain Criteria (RDoC) as a basis for research related to substance use. Effective assessment and consideration of co-occurring disorders are covered as well. Although the prognosis of SUD varies by an individual's environment and circumstances, a modal developmental course for SUD is discussed. Finally, a curated list of nationally recognized resources including hotlines, treatment locators, informational sites, and support groups is provided, along with tools to compile local resources. By addressing these aspects of adolescent SUD, the research team offers a broader view of its prevalence in the United States, key warning signs and comorbidities, and possible assessments and treatments for adolescents with SUD.

Analytical chemistry is bound to face growing challenges in the near future, especially for the quantification of trace analytes in complex matrices [...]

Annually, severe weather phenomena are responsible for tens of thousands of deaths and tens of billions of dollars of damage around the world. In Brazil, unlike other hydrometeorological events, severe atmospheric events are random and, therefore, do not have a sociospatial pattern. Because of that, there is a significant motivation to improve the prediction techniques for this kind of events, using high resolution numerical models. A large amount of high-quality observational data is required, including lightning data in a very short-range. In addition, the detection of lightning flashes produced by storms is important for a wide variety of applications and in some areas of scientific research, which include the understanding of the human action on the climate and how the climate change can affect the behavior of storms in long range. One method to monitor the lightning flashes is the implementation of sensors in satellites to obtain data. In this sense, the objective of the RaioSat project is to develop national technology for detecting lightning flashes from the space, in order to complement the existing data from the ground detection network, BrasilDAT. The main objective of this article is to present a methodology for the development of the RaioSat mission including some parts of the preliminary design and operational modes. Additionally, the article describes the expected results and the continuity of the project and a preliminary analysis of a constellation for future projects.

BackgroundDue to the high prevalence of malnutrition among hospitalized patients, screening and assessment of nutritional status should be routinely performed upon hospital admission. The main objective of this observational study was to evaluate the prevalence of and the risk for malnutrition, as identified by using three nutritional screening tests, and to observe whether some anthropometric and functional parameters used for nutritional evaluation were related to these test scores.MethodsThis single-center observational study included 207 patients admitted from the emergency department for hospitalization in either the internal medicine or surgery units of our institution from September 2017 to December 2018. The prevalence of malnutrition among this patient sample was evaluated by using the Nutritional Risk Screening (NRS-2002), the Subjective Global Assessment (SGA) and the Global Leadership Initiative on Malnutrition (GLIM) criteria. Body mass index (BMI), bioimpedance analysis (BIA), handgrip strength (HGS) and calf circumference (CC) assessments were also performed.ResultsAccording to the NRS-2002, 93% of the patients were at no risk or at low nutritional risk (NRS score < 3), and 7% were at a high nutritional risk (NRS score ≥ 3). On the other hand, according to the SGA, 46.3% of the patients were well-nourished (SGA-a), 49.8% were moderately malnourished (SGA-b), and 3.9% were severely malnourished (SGA-c). Finally, according to the GLIM criteria, 18% patients were malnourished. Body weight, body mass index (BMI), phase angle (PhA), CC and HGS were significantly lower in the patients with NRS scores ≥ 3, SGA-c and in patients with stage 1 and stage 2 malnutrition, according to the GLIM criteria.ConclusionThe NRS-2002, the SGA and the GLIM criteria appear to be valuable tools for the screening and assessment of nutritional status. In particular, the lowest NRS-2002, SGA and GLIM scores were associated with the lowest PhA and CC. Nevertheless, a weekly re-evaluation of patients with better screening and assessment scores is recommended to facilitate early detection of changes in nutritional status.

Abstract Background Unity Elekta is a unique magnetic resonance (MR)-linac that conjugates a 1.5 Tesla MR unit with a 7 MV flattening filter free accelerator.A prospective observational study for the clinical use of Elekta Unity is currently ongoing in our department. Herein, we present our preliminary report on the feasibility, quality of life, and patient-reported outcomes measures (PROMs) for localized prostate cancer (PC) treated with stereotactic body radiotherapy (SBRT). Methods The SBRT protocol consisted of a 35 Gy schedule delivered in 5 fractions within 2 weeks. Toxicity and quality of life (QoL) were assessed at baseline and after treatment using the Common Terminology Criteria for Adverse Events v5.0, International Prostatic Symptoms Score (IPSS), ICIQ-SF, IIEF-5, and EORTC-QLQ-C30 and PR-25 questionnaires. Results Between October 2019 and January 2020, 25 patients with localized PC were recruited. The median age was 68 years (range, 54–82); 4 were low risk, 11 favorable intermediate risk (IR) and 10 unfavorable IR. Median iPSA was 6.8 ng/ml (range, 1–19), and 9 of these patients (36%) received concurrent androgen deprivation therapy. Median prostate volume was 36 cc (range, 20–61); median baseline IPSS was 5 (range, 0–10). Median time for fraction was 53 min (range, 34–86); adaptive strategy with daily critical structure and target re-contouring and daily replanning (adapt to shape) was performed in all cases. No grade ≥ 3 adverse event was observed, three patients (12%) reported grade 2 acute genitourinary toxicity (urinary frequency, urinary tract pain and urinary retention), while only one patient reported mild rectal pain. No relevant deteriorations were reported in PROMs. Conclusion To the best of our knowledge, this is the first experience reporting feasibility, clinician-reported outcome measurements, and PROMs for 1.5 T MR-guided adaptive SBRT for localized prostate cancer. The preliminary data collected here report optimal safety and excellent tolerability, as also confirmed by PROMs questionnaires. Moreover, the data on technical feasibility and timing of online daily adapted planning and delivery are promising. More mature data are warranted. Trial registration Date of approval April 2019 and numbered MRI/LINAC n°23,748.

Human norovirus is the first cause of foodborne disease worldwide, leading to extensive outbreaks of acute gastroenteritis, and causing around 200,000 children to die annually in developing countries. No specific vaccines or antiviral agents are currently available, with therapeutic options limited to supportive care to prevent dehydration. The infection can become severe and lead to life-threatening complications in young children, the elderly and immunocompromised individuals, leading to a clear need for antiviral agents, to be used as treatments and as prophylactic measures in case of outbreaks. Due to the key role played by the viral RNA-dependent RNA polymerase (RdRp) in the virus life cycle, this enzyme is a promising target for antiviral drug discovery. In previous studies, following in silico investigations, we identified different small-molecule inhibitors of this enzyme. In this study, we rationally modified five identified scaffolds, to further explore structure–activity relationships, and to enhance binding to the RdRp. The newly designed compounds were synthesized according to multiple-step synthetic routes and evaluated for their inhibition of the enzyme in vitro. New inhibitors with low micromolar inhibitory activity of the RdRp were identified, which provide a promising basis for further hit-to-lead optimization.

Purpose: The present study reports the preliminary outcomes in terms of adverse events and quality of life in the first 100 patients treated with 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. Methods: From October 2019 to December 2020, 100 patients, enrolled in a prospective study, received MR-guided SBRT for prostate cancer. Rectal spacer insertion was optional and administered in 37 patients. In total, 32 patients received androgen deprivation therapy in accordance with international guidelines. A prospective collection of data regarding toxicity and quality of life was performed. Results: The median age was 71 years (range, 52–84). The median total dose delivered was 35 Gy (35–36.25 Gy) in five sessions, either on alternate days (n = 25) or consecutive days (n = 75). For acute toxicity, we recorded: seven cases of acute G2 urinary pain and four cases of G2 gastrointestinal events. The median follow-up was 12 months (3–20), recording three late G2 urinary events and one G3 case, consisting of a patient who required a TURP 8 months after the treatment. For gastrointestinal toxicity, we observed 3 G ≥ 2 GI events, including one patient who received argon laser therapy for radiation-induced proctitis. Up to the last follow-up, all patients are alive and with no evidence of biochemical relapse, except for an M1 low-volume patient in distant progression two months after radiotherapy. QoL evaluation reported a substantial resolution of any discomfort within the second follow-up after radiotherapy, with the only exception being sexual items. Notably, after one year, global health items were improved compared to the baseline assessment. Conclusions: This study reports very promising outcomes in terms of adverse events and QoL, supporting the role of 1.5T MR-guided SBRT for prostate cancer. To date, this series is one of the first and largest available in the literature. Long-term results are warranted.

Tumor biopsy is still the gold standard for diagnosing and prognosis renal cell carcinoma (RCC). However, its invasiveness, costs, and inability to accurately picture tumor heterogeneity represent major limitations to this procedure. Analysis of circulating cell-free DNA (cfDNA) is a non-invasive cost-effective technique that has the potential to ease cancer detection and prognosis. In particular, a growing body of evidence suggests that cfDNA could be a complementary tool to identify and prognosticate RCC while providing contemporary mutational profiling of the tumor. Further, recent research highlighted the role of cfDNA methylation profiling as a novel method for cancer detection and tissue-origin identification. This review synthesizes current knowledge on the diagnostic, prognostic, and predictive applications of cfDNA in RCC, with a specific focus on the potential role of cell-free methylated DNA (cfMeDNA).