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Daytime atmospheric boundary layer (ABL) dynamics—including potential temperature budgets, water vapour budgets, and entrainment rates—are presented from in situ flight data taken on six afternoons near Fresno in the San Joaquin Valley (SJV) of California during July/August 2016. The flights took place as a part of the California Baseline Ozone Transport Study aimed at investigating transport pathways of air entering the Central Valley from offshore and mixing down to the surface. Midday entrainment velocity estimates ranged from 0.8 to 5.4 cm s−1 and were derived from a combination of continuously determined ABL heights during each flight and model-derived subsidence rates, which averaged -2.0 cm s−1 in the flight region. A strong correlation was found between entrainment velocity (normalized by the convective velocity scale) and an inverse bulk ABL Richardson number, suggesting that wind shear at the ABL top plays a significant role in driving entrainment. Similarly, we found a strong correlation between the entrainment efficiency (the ratio of entrainment to surface heat fluxes with an average of 0.23 ± 0.15) and the wind speed at the ABL top. We explore the synoptic conditions that generate higher winds near the ABL top and propose that warm anomalies in the southern Sierra Nevada mountains promote increased entrainment. Additionally, a method is outlined to estimate turbulence kinetic energy, convective velocity scale (w*), and the surface sensible heat flux in the ABL from a slow, airborne wind measurement system using mixed-layer similarity theory.

Purpose Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. Methods PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. Results Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59–88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. Conclusion The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

Strychnine is a natural product that, through isolation, structural elucidation and synthetic efforts, shaped the field of organic chemistry. Currently, strychnine is used as a pesticide to control rodents1 because of its potent neurotoxicity2,3. The polycyclic architecture of strychnine has inspired chemists to develop new synthetic transformations and strategies to access this molecular scaffold4, yet it is still unknown how plants create this complex structure. Here we report the biosynthetic pathway of strychnine, along with the related molecules brucine and diaboline. Moreover, we successfully recapitulate strychnine, brucine and diaboline biosynthesis in Nicotiana benthamiana from an upstream intermediate, thus demonstrating that this complex, pharmacologically active class of compounds can now be harnessed through metabolic engineering approaches.

Background Racial, ethnic, religious, and cultural diversity in Australia is rapidly increasing. Although Indigenous Australians account for only approximately 3.5% of the country’s population, over 50% of Australians were born overseas or have at least one migrant parent. Migration accounts for over 60% of Australia’s population growth, with migration from Asia, Sub-Saharan African and the Americas increasing by 500% in the last decade. Little is known about Australian mental health care practitioners’ attitudes toward this diversity and their level of cultural competence. Aim Given the relationship between practitioner cultural competence and the mental health outcomes of non-White clients, this study aimed to identify factors that influence non-White and White practitioners’ cultural competence. Methods An online questionnaire was completed by 139 Australian mental health practitioners. The measures included: the Balanced Inventory of Desirable Responding (BIDR); the Multicultural Counselling Inventory (MCI); and the Color-blind Racial Attitudes Scale (CoBRAS). Descriptive statistics were used to summarise participants’ demographic characteristics. One-way ANOVA and Kruskal–Wallis tests were conducted to identify between-group differences (non-White compared to White practitioners) in cultural competence and racial and ethnic blindness. Correlation analyses were conducted to determine the association between participants’ gender or age and cultural competence. Hierarchical multiple regression analysis was conducted to predict cultural competence. Results The study demonstrates that non-White mental health practitioners are more culturally aware and have better multicultural counselling relationships with non-White people than their White counterparts. Higher MCI total scores (measuring cultural competence) were associated with older age, greater attendance of cultural competence-related trainings and increased awareness of general and pervasive racial and/or ethnic discrimination. Practitioners with higher MCI total scores were also likely to think more highly of themselves (e.g., have higher self-deceptive positive enhancement scores on the BIDR) than those with lower MCI total scores. Conclusion The findings highlight that the current one-size-fits-all and skills-development approach to cultural competence training ignores the significant role that practitioner diversity and differences play. The recommendations from this study can inform clinical educators and supervisors about the importance of continuing professional development relevant to practitioners’ age, racial/ethnic background and practitioner engagement with prior cultural competence training.

The ageing of the population is reshaping a large part of the economic and social order, with pervasive and transversal consequences that reflect on production, consumption, labour, and especially on welfare. To govern a development of this kind, it is essential to have an innovative approach, capable of stimulating targeted and systematic policies, and capable of facing the structural change of ageing, transforming it from a burden to a resource for our society. Since the beginning of the new millennium, there has been a gradual attention to the phenomenon of demographic ageing at an international level, which has prompted the European Union to proclaim 2012 as the European Year for Active Ageing and Solidarity between Generations. Recommendations from the international organizations to individual countries on adopting active ageing policies led to the creation of the Active Ageing Index (AAI). Istat has extensively contributed to the AAI interacting with its international partners (UNECE and the European Commission).There is no doubt that AAI is a useful tool, both for measuring achieved progress in the area of active ageing, and for promoting the implementation and the evaluation of policies aimed at improving any potential aspect that does not show satisfactory results. AAI consists of four dimensions and 22 indicators. Using nationally representative data, it was first disseminated in Italy as the product of an experiment intended to provide overall and individual domain data on a subnational level placing Istat at the forefront among European statistical institutes.

Oral health care can be a difficult experience for a child with Autism Spectrum Disorder (ASD), for their family and for the dentist. The purpose of this study is to provide an understanding of the challenges experienced by the three aforementioned figures during oral care treatment. A cohort of 275 parents of typical development children (TD), 57 parents of children with ASD (3–15 years old) and by 61 dentists, completed two different multiple choices questionnaires. The data obtained show a great difficulty in the treatment of children with ASD as seen by the dentists and by the parents. This is due to: caregivers’ demographic issues; difficulties encountered before and during the dental examination; scarce presence of experts in ASD treatment.

Earliest craniates possess a newly enlarged, elaborated forebrain with new cell types and neuronal networks. A key question in vertebrate evolution is when and how this cerebral expansion took place. The exon-junction complex (EJC) plays an essential role in mRNA processing of all Eukarya. Recently, it has been proposed that the EJC represses recursive RNA splicing in Deuterostomes, with implication in human brain diseases like microcephaly and depression. However, the EJC or EJC subunit contribution to brain development in non-vertebrate Deuterostomes remained unknown. Being interested in the evolution of chordate characters, we focused on the model species, Branchiostoma lanceolatum (Cephalochordata) and Ciona robusta (Tunicata), with the aim to investigate the ancestral and the derived expression state of Magoh orthologous genes. This study identifies that Magoh is part of a conserved syntenic group exclusively in vertebrates and suggests that Magoh has experienced duplication and loss events in mammals. During early development in amphioxus and ascidian, maternal contribution and zygotic expression of Magoh genes in various types of progenitor cells and tissues are consistent with the condition observed in other Bilateria. Later in development, we also show expression of Magoh in the brain of cephalochordate and ascidian larvae. Collectively, these results provide a basis to further define what functional role(s) Magoh exerted during nervous system development and evolution.

Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.

BackgroundHealthcare workers (HCW) are at increased risk of being infected with SARS-CoV-2, yet limited information is available on risk factors of infection.MethodsWe pooled data on occupational surveillance of 10,654 HCW who were tested for SARS-CoV-2 infection in six Italian centers. Information was available on demographics, job title, department of employment, source of exposure, use of personal protective equipment (PPE), and COVID-19-related symptoms. We fitted multivariable logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI).FindingsThe prevalence of infection varied across centers and ranged from 3.0% to 22.0%, being strongly correlated with that of the respective areas. Women were at lower risk of infection compared to men. Fever, cough, dyspnea and malaise were the symptoms most strongly associated with infection, together with anosmia and ageusia. No differences in the risk of infection were detected between job titles, or working in a COVID-19 designated department. Reported contact with a patient inside or outside the workplace was a risk factor. Use of a mask was strongly protective against risk of infection as was use of gloves. The use of a mask by the source of exposure (patient or colleague) had an independent effect in reducing infection risk.

Recent studies have focused their attention on conjunctivitis as one of the symptoms of coronavirus disease 2019 (COVID-19). Therefore, tear samples were taken from COVID-19 patients and the presence of SARS-CoV-2 was evidenced using Real Time reverse transcription polymerase chain reaction. The main aim of this study was to analyze mRNA expression in the tears of patients with COVID-19 compared with healthy subjects using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 25 genes that differ statistically between healthy individuals and patients affected by COVID-19. In particular, the NGS analysis identified the presence of several genes involved in B cell signaling and keratinization. In particular, the genes involved in B cell signaling were downregulated in the tears of COVID-19 patients, while those involved in keratinization were upregulated. The results indicated that SARS-CoV-2 may induce a process of ocular keratinization and a defective B cell response.

Background Goats (Capra hircus), one of the first domesticated species, are economically important for milk and meat production, and their broad geographical distribution reflects their successful adaptation to diverse environmental conditions. Despite the relevance of this species, the genetic research on the goat traits is limited compared to other domestic species. Thanks to the latest goat reference genomic sequence (ARS1), which is considered to be one of the most continuous assemblies in livestock, we deduced the genomic structure of the T cell receptor beta (TRB) and gamma (TRG) loci in this ruminant species. Results Our analyses revealed that although the organization of the goat TRB locus is broadly similar to that of the other artiodactyl species, with three in-tandem D-J-C clusters located at the 3′ end, a complex and extensive series of duplications have occurred in the V genes at the 5′ end, leading to a marked expansion in the number of the TRBV genes. This phenomenon appears to be a feature of the ruminant lineage since similar gene expansions have also occurred in sheep and cattle. Likewise, the general organization of the goat TRG genes is typical of ruminant species studied so far, with two paralogous TRG loci, TRG1 and TRG2, located in two distinct and distant positions on the same chromosome as result of a split in the ancestral locus. Each TRG locus consists of reiterated V-J-J-C cassettes, with the goat TRG2 containing an additional cassette relative to the corresponding sheep and cattle loci. Conclusions Taken together, these findings demonstrate that strong evolutionary pressures in the ruminant lineage have selected for the development of enlarged sets of TRB and TRG genes that contribute to a diverse T cell receptor repertoire. However, differences observed among the goat, sheep and cattle TRB and TRG genes indicate that distinct evolutionary histories, with independent expansions and/or contractions, have also affected each ruminant species.

Background COVID-19 in Italy has led to the need to reorganize hospital protocols with a significant risk of interruption to cancer treatment programs. In this report, we will focus on a management model covering the two phases of the COVID-19 emergency, namely lockdown-phase I and post-lockdown-phase II. Methods The following steps were taken in the two phases: workload during visits and radiotherapy planning, use of dedicated routes, measures for triage areas, management of suspected and positive COVID-19 cases, personal protective equipment, hospital environments and intra-institutional meetings and tumor board management. Due to the guidelines set out by the Ministry of Health, oncological follow-up visits were interrupted during the lockdown-phase I; consequently, we set about contacting patients by telephone, with laboratory and instrumental exams being viewed via telematics. During the post-lockdown-phase II, the oncological follow-up clinic reopened, with two shifts operating daily. Results By comparing our radiotherapy activity from March 9 to May 4 2019 with the same period in 2020 during full phase I of the COVID-19 emergency, similar results were achieved. First radiotherapy visits, Simulation Computed Tomography and Linear Accelerator treatments amounted to 123, 137 and 151 in 2019 compared with 121, 135 and 170 in 2020 respectively. There were no cases of COVID-19 positivity recorded either in patients or in healthcare professionals, who were all negative to the swab tests performed. Conclusion During both phases of the COVID-19 emergency, the planned model used in our own experience guaranteed both continuity in radiotherapy treatments whilst neither reducing workload nor interrupting treatment and, as such, it ensured the safety of cancer patients, hospital environments and staff.

Background Exosomes are extracellular vesicles containing a variety of biological molecules including microRNAs (miRNAs). We have recently demonstrated that certain miRNA species are selectively and highly enriched in pancreatic cancer exosomes with miR-1246 being the most abundant. Exosome miRNAs have been shown to mediate intercellular communication in the tumor microenvironment and promote cancer progression. Therefore, understanding how exosomes selectively enrich specific miRNAs to initiate exosome miRNA signaling in cancer cells is critical to advancing cancer exosome biology. Results The aim of this study was to identify RNA binding proteins responsible for selective enrichment of exosome miRNAs in cancer cells. A biotin-labeled miR-1246 probe was used to capture RNA binding proteins (RBPs) from PANC-1 cells. Among the RBPs identified through proteomic analysis, SRSF1, EIF3B and TIA1 were highly associated with the miR-1246 probe. RNA immunoprecipitation (RIP) and electrophoretic mobility shift assay (EMSA) confirmed the binding of SRSF1 to miR-1246. Lentivirus shRNA knockdown of SRSF1 in pancreatic cancer cells selectively reduced exosome miRNA enrichment whereas GFP-SRSF1 overexpression enhanced the enrichment as analyzed by next generation small RNA sequencing and qRT-PCR. miRNA sequence motif analysis identified a common motif shared by 36/45 of SRSF1-associated exosome miRNAs. EMSA confirmed that shared motif decoys inhibit the binding of SRSF1 to the miR-1246 sequence. Conclusions We conclude that SRSF1 mediates selective exosome miRNA enrichment in pancreatic cancer cells by binding to a commonly shared miRNA sequence motif. Graphical abstract