Search

Erosion and entrainment of material by debris flows determine debris-flow volume growth and therefore hazard potential. Recent advances in field, laboratory, and modelling studies have distilled two driving forces behind debris-flow erosion; impact and shear forces. A third factor influencing the (relative) importance of these forces is the viscosity and abundance of the interstitial fluid in the debris flow and the bed. However, how erosion and these forces depend on the composition of the debris flow itself and the composition of the bed remains unclear. Here, we present results of small-scale flume experiments with a loosely packed erodible bed that highlight the far-reaching effects of debris-flow and bed composition on erosion processes and magnitude. We quantify the effects of gravel, clay, and solid fraction in the debris flow on bed erosion. In addition, we quantify the effects of water and clay content of the unconsolidated bed on erosion by a debris flow. We show that debris flow erosion increases linearly when the gravel fraction of a debris flow is increased, which is linked to an increase in both impact and shear forces. We find that debris flow erosion, and the related forces, are non-linearly impacted by the clay and water content of the debris flow and those of the bed. For both the clay content of the debris flow and the bed, an optimum in erosion exists around a specific clay percentage that does not directly relate to an optimum in either shear or impact forces. When the water content of the bed and/or the debris flow is increased, erosion becomes largest when supersaturated conditions occur. These conditions are unrelated to the magnitude of the two erodible forces. This shows that both clay and water content affect erosion by affecting the transfer of pore pressures from the debris flow to the bed. We can therefore conclude that impact and shear forces dictate debris flow erosion in most cases but that their (relative) importance is significantly altered by the means and effectivity of pore pressure transfer from the debris flow to the bed. The latter is highly influenced by the viscosity and abundance of the interstitial fluid of the debris flow and the composition of the bed.

Despite being a fundamental concept in biology, evolution continues to be one of the most challenging topics to teach in science education. Ideas of evolution emphasising anatomical or behavioural features of individuals, as opposed to the interplay between genetics and the environment, are reinforced through language and culture, making them robust and persistent in the student population at all educational levels. Model-based reasoning has been reported to be useful for students to make sense of process-based science content, combining epistemological with linguistic and value dimensions. However, there is a dearth of evidence in biology education showing how modelling can instigate epistemological maturity, specifically about issues of agency and design in evolution by natural selection. Drawing on this perspective, this study focuses on describing the nature of students' ideas while modelling the resistance developed by a population of mosquitoes in a lagoon after an insecticide is introduced. Data collection includes students' written reports and drawings, which were analysed with content and discourse analysis. The findings show that, at first, students believed adaptation to feature at will was a behavioural characteristic instigated by a pre-existing design. After modelling the process of natural selection, the explanations appeared to improve (from Lamarckian to Neo-Darwinian views), and most groups showed accurate explanations about adaptation.

Monica Valente,1 Maura Colucci,2 Virginia Vegni,3 Valentina Croce,2 Cristiana Bellan,4 Giulia Rossi,1 Giulia Gibilisco,2 Francesco Frongia,2 Raffaella Guazzo,4 Claudia Ghiribelli,5 Elena Bargagli,6 Vinno Savelli,7 Matteo Ravara,2 Tommaso Sani,2 Elena Simonetti,2 Michele Maio,1– 3 Luana Calabrò,8,9 Anna Maria Di Giacomo1– 3 1Department of Oncology, Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy; 2Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy; 3NIBIT Foundation Onlus, Siena, Italy; 4Department of Medical Biotechnology, Pathology Unit, University Hospital of Siena, Siena, Italy; 5Cardio-Thoracic-Vascular Department, Interventional and Diagnostic Bronchoscopy Unit, University Hospital of Siena, Siena, Italy; 6Department of Medicine, Surgery and Neurosciences, Respiratory Diseases Unit, University of Siena, Siena, Italy; 7Department of Medicine, Surgery and Neurosciences, Surgical Oncology Unit, University Hospital of Siena, Siena, Italy; 8Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 9Department of Medical Oncology, University Hospital of Ferrara, Ferrara, ItalyCorrespondence: Anna Maria Di Giacomo, Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy, Tel +39-0577-586336, Fax +39-0577-586303, Email annamaria.digiacomo@unisi.itPurpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy.Patients and Methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification.Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4– 51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity.Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN. Keywords: immunotherapy, immune-checkpoint inhibitors, immune-mediated pneumonitis, cancer

Abstract Background The rise of a new generation of intelligent neuroprostheses, brain-computer interfaces (BCI) and adaptive closed-loop brain stimulation devices hastens the clinical deployment of neurotechnologies to treat neurological and neuropsychiatric disorders. However, it remains unclear how these nascent technologies may impact the subjective experience of their users. To inform this debate, it is crucial to have a solid understanding how more established current technologies already affect their users. In recent years, researchers have used qualitative research methods to explore the subjective experience of individuals who become users of clinical neurotechnology. Yet, a synthesis of these more recent findings focusing on qualitative methods is still lacking. Methods To address this gap in the literature, we systematically searched five databases for original research articles that investigated subjective experiences of persons using or receiving neuroprosthetics, BCIs or neuromodulation with qualitative interviews and raised normative questions. Results 36 research articles were included and analysed using qualitative content analysis. Our findings synthesise the current scientific literature and reveal a pronounced focus on usability and other technical aspects of user experience. In parallel, they highlight a relative neglect of considerations regarding agency, self-perception, personal identity and subjective experience. Conclusions Our synthesis of the existing qualitative literature on clinical neurotechnology highlights the need to expand the current methodological focus as to investigate also non-technical aspects of user experience. Given the critical role considerations of agency, self-perception and personal identity play in assessing the ethical and legal significance of these technologies, our findings reveal a critical gap in the existing literature. This review provides a comprehensive synthesis of the current qualitative research landscape on neurotechnology and the limitations thereof. These findings can inform researchers on how to study the subjective experience of neurotechnology users more holistically and build patient-centred neurotechnology.

Family-integrated care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of an augmented FICare program, FICare Plus, in critically ill infants in the first few weeks of life. Resources were specifically developed for staff and parents to support earlier parental engagement in infant care. Infant health outcomes and standardized measures of parental stress, anxiety and parenting self-efficacy were also collected using standardized questionnaires: State -Trait Anxiety Inventory (STAI), Parental Stressor Scale: NICU (PSS: NICU), Perceived Parenting Self-Efficacy Tool and Family Centered Care Survey. The t-test or Wilcoxon rank-sum test were used to compare continuous variables, while the Chi-square or Fisher exact test were used for categorical variables, respectively. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in standard care (SC) and 24 in the FICare Plus group. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infants with no increase in adverse events and no increase in parental stress. Parents in the FICare Plus cohort felt confident to participate in their infants care. The staff also found this model of care acceptable and well adopted. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrollment (87 (67-94) vs. 70.5 (66-86); p-value 0.22). However, the scores prior to discharge were lower in FICare Plus group (78 (71-90) vs. 63 (52-74.5); p-value 0.02). This pilot study showed that it is feasible and safe to implement family-integrated care in critically ill infants.

L’articolo presenta i risultati di un’indagine che ha coinvolto persone con disabilità e studenti universitari sul tema della città pubblica inclusiva. A fare da cornice il progetto VIVIinclusi, promosso dal Politecnico di Milano – Polo territoriale di Lecco in collaborazione con il Comune di Lecco ed Enti del Terzo Settore. Il progetto ha lo scopo di attivare percorsi di ricerca-azione e di coproduzione con gli attori del territorio per individuare strategie e strumenti di innovazione urbana per una città pubblica inclusiva. L’indagine si è avvalsa del metodo delle passeggiate sensobiografiche e ha coinvolto persone con disabilità frequentanti i servizi socio-educativi diurni e residenziali al fine di conoscere il loro punto di vista sulla città. La ricerca, oltre ad avere fornito elementi per la seconda fase di co-progettazione, ha permesso di riflettere criticamente sulla qualità inclusiva della città e dei servizi.

Background: Early thromboprophylaxis does not prevent hospital admissions and death among outpatients with symptomatic COVID-19. Its impact on long-term outcomes, including long COVID symptoms and performance status, is unknown. Objectives: To assess the long-term effects of thromboprophylaxis given at the time of acute COVID-19 in outpatients. Methods: The OVID (enoxaparin for outpatients with COVID-19) trial randomized outpatients older than 50 years with acute COVID-19 to receive either subcutaneous enoxaparin 40 mg once daily for 14 days or standard of care (no thromboprophylaxis). In this follow-up study, we assessed the 2-year outcomes, including all-cause hospitalization and death, cardiovascular events, long COVID symptoms, and functional limitations based on the Post–COVID-19 Functional Status (PCFS) scale and EuroQol-5 Dimensions-5 Levels scale. Results: Of 469 potentially eligible patients, 468 survived, of whom 439 (mean age 59 years; 54% men) participated in the Post-OVID study. There was no difference in terms of hospitalization and death (8.3% in the treatment group vs 10% in controls; relative risk, 0.83; 95% CI, 0.5-1.5) and of cardiovascular events between groups. The risk of presenting with long COVID symptoms was similar in the 2 groups (44% in the treatment group vs 47% in the standard of care group), with no difference between groups also concerning individual symptoms. A PCFS grade of 1 to 3, indicating light-to-moderate functional limitation, was recorded in 15% of patients in each group (odds ratio, 0.98; 95% CI, 0.6-1.7). No patients reported severe limitations (PCFS grade 4). Median EuroQol visual analog scale score was 85 on 100 points (IQR, 80-90 for the standard of care group and 75-90 for the enoxaparin group). Conclusion: Early thromboprophylaxis does not improve long-term, 2-year clinical and functional outcomes among symptomatic ambulatory patients with acute COVID-19.

Addressing the critical question posed by Gudrun Jonsdottir and Anne Kristine Byhring who are asking what place for a common future in the science classroom, this paper focuses on and expands on the construct of "dialogical space." Not simply as an abstract concept to describe the presence of divergent ideas or the exchange of idioms, but a space filled with metaphors and material artefacts that exist "in the world." On this basis, science education takes seriously the affordances of sensorial perception in space, as physical and material "doings," arising from and deeply concerned with the lived experiences of people. By making visible the material relations that give life to human experience, and by giving life to different imaginations, science education can thus become profoundly dialogical: turning away from the expectation of sameness, it houses in itself the invitation of taking authorship and to give form, that being a narrative, a personal journey, or a different way of looking at the world. This is what I call gesturing in plain sight, a science education that critically engages with material artefacts and their relations; one that inhabits the realm of the symbolic and the experiential, and one that speaks to sustainable futures in general, repurposing and reconceiving the work of science education in particular.

Our incomplete knowledge of maternal–fetal interface (MFI) physiology impedes a better understanding of the pathological mechanisms leading to pregnancy complications, such as pre-eclampsia and fetal growth restriction. At the MFI, uterine natural killer (uNK) cells do not attack fetal cells but engage in crosstalk with both fetal and maternal cells to support feto-placental development. However, mother and fetus are genetically half-mismatched and certain combinations of variable immune genes—human leukocyte antigens (HLAs) and killer-cell immunoglobulin-like receptor (KIR), indeed, the most variable gene sets in the genome—associate with pregnancy outcomes, suggesting that these interactions regulate uNK cell function. How do these interactions influence the physiology and pathology at the MFI? Uterine NK cell function is regulated by both maternal and fetal Major Histocompatibility Complex (MHC); however, evidence for fetal cells educating uNK cells is lacking, and new evidence shows that maternal rather than fetal MHC class I molecules educate uNK cells. Furthermore, uNK cell education works through self-recognition by the ancient and conserved NKG2A receptor. Pregnant mice lacking this receptor produce normal litter sizes, but a significant portion of the offspring have low birthweight and abnormal brain development. Evidence from a genome-wide association study of over 150,000 human pregnancies validates the finding because women whose NKG2A receptor is genetically determined to engage their own MHC class I molecules are exposed to lower risk of developing pre-eclampsia, suggesting that maternal uNK cell education is a pre-requisite for a healthy pregnancy and, likely, for healthy offspring too.

Background/Objectives: Cognitive impairment in spinocerebellar ataxia patients has been reported since the early-disease stage. We aimed to assess cognitive differences in SCA1 and SCA2 patients. Methods: We performed neuropsychological (NPS) and neurophysiological (auditory event-related potentials, aERPs) assessments in 16 SCA1 and 18 SCA2 consecutive patients. Furthermore, clinical information (age at onset, disease duration, motor disability) was collected. Results: NPS tests yielded scores in the normal range in both groups but with lower scores in the Frontal Assessment Battery (p < 0.05) and Visual Analogue Test for Anosognosia for motor impairment (p < 0.05) in SCA1, and the Trail Making Test (p < 0.01), Raven’s progressive matrices (p < 0.01), Stroop (p < 0.05), and emotion attribution tests (p < 0.05) in SCA2. aERPs showed lower N100 amplitude (p < 0.01) and prolonged N200 latency (p < 0.01) in SCA1 compared with SCA2. Clinically, SCA2 had more severe motor disability than SCA1 in the Assessment and Rating of Ataxia Scale. Conclusions: SCA2 showed more significant difficulties in attentional, visuospatial, and emotional function, and greater motor impairment. In contrast, SCA1 showed less cognitive flexibility/phasic ability, probably affected by a more severe degree of dysarthria. The same group revealed less neural activity during nonconscious attentional processing (N100-N200 data), suggesting greater involvement of sensory pathways in discriminating auditory stimuli. NFS did not correlate with NPS findings, implying an independent relationship. However, the specific role of the cerebellum and cerebellar symptoms in NPS test results deserves more focus.

To date, not many studies have presented evidence of SARS-CoV-2 infecting the female reproductive system. Furthermore, so far, no effect of the administration of anti-COVID 19 vaccines has been reported to affect the quality of oocytes retrieved from women who resorted to assisted reproduction technology (ART). The FF metabolic profiles of women who had been infected by SARS-CoV-2 before IVF treatments or after COVID-19 vaccination were examined by 1H NMR. Immunochemical characterization of proteins and cytokines involved in the redox and inflammatory pathways was performed. The increased expression of SOD2 and NQO1, the lack of alteration of IL-6 and CXCL10 levels, as well as the increased expression of CD39, suggested that, both sharing similar molecular mechanisms or proceeding along different routes, the redox balance is controlled in the FF of both vaccinated and recovered women compared to controls. The lower amount of metabolites known to have proinflammatory activity, i.e., TMAO and lipids, further supported the biochemical results, suggesting that the FF microenvironment is controlled so as to guarantee oocyte quality and does not compromise the outcome of ART. In terms of the number of blastocysts obtained after ICSI and the pregnancy rate, the results are also comforting.

Noradrenergic activation of the basolateral amygdala (BLA) by emotional arousal enhances different forms of recognition memory via functional interactions with the insular cortex (IC). Human neuroimaging studies have revealed that the anterior IC (aIC), as part of the salience network, is dynamically regulated during arousing situations. Emotional stimulation first rapidly increases aIC activity but suppresses it in a delayed fashion. Here, we investigated in male Sprague-Dawley rats whether the BLA influence on recognition memory is associated with an increase or suppression of aIC activity during the postlearning consolidation period. We first employed anterograde and retrograde viral tracing and found that the BLA sends dense monosynaptic projections to the aIC. Memory-enhancing norepinephrine administration into the BLA following an object training experience suppressed aIC activity 1 h later, as determined by a reduced expression of the phosphorylated form of the transcription factor cAMP response element-binding (pCREB) protein and neuronal activity marker c-Fos. In contrast, the number of perisomatic γ-aminobutyric acid (GABA)ergic inhibitory synapses per pCREB-positive neuron was significantly increased, suggesting a dynamic up-regulation of GABAergic tone. In support of this possibility, pharmacological inhibition of aIC activity with a GABAergic agonist during consolidation enhanced object recognition memory. Norepinephrine administration into the BLA did not affect neuronal activity within the posterior IC, which receives sparse innervation from the BLA. The evidence that noradrenergic activation of the BLA enhances the consolidation of object recognition memory via a mechanism involving a suppression of aIC activity provides insight into the broader brain network dynamics underlying emotional regulation of memory.

IntroductionTreatment options in patients with myelofibrosis (MF) presenting with thrombocytopenia are limited. Final results of the phase 2 study (NCT01348490) of ruxolitinib in patients with MF and low baseline platelet counts (50 - 100 × 109/L) are reported.Patients and methodsPatients received ruxolitinib 5 mg twice daily (BID), with optional up-titration to a maximum of 15 mg BID, provided platelet count remained ≥40 × 109/L. Assessments included spleen volume and length, Total Symptom Score (TSS), quality of life, and safety.ResultsOf 66 patients, 52 (78.8%) completed the first 24 weeks of treatment. Median (range) percentage change from baseline in spleen volume and TSS (coprimary endpoints) were -20.5% (-55.8% to 38.5%, n=51) and -39.8% (-98.6% to 226.4%, n=53), respectively; greatest median reductions were in the 10 mg BID final titrated dose group. Of patients achieving ≥35% or ≥10% reduction in spleen volume, 8/11 (72.7%) and 21/34 (61.8%), respectively, were in the 10 mg BID final titrated dose group. Thirty-seven of 65 patients (56.9%) had ≥20% improvement in TSS, and 35/66 patients (53.0%) were Patient Global Impression of Change responders. Treatment-emergent adverse events led to dose interruption in 17/66 patients (25.8%), most commonly thrombocytopenia (n=3).ConclusionA starting dose of ruxolitinib 5 mg BID with gradual up-titration and dose optimization based on hematologic parameters and response was efficacious and generally well-tolerated in patients with MF and low platelet counts. Median improvement in spleen volume and symptoms was greatest for patients receiving ruxolitinib 10 mg BID.