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BackgroundIncreased success in the treatment of hematological cancers contributed to the increase of 5-year survival for most adolescent and young adults (AYAs) with these tumours. However, as 5-year survival increased, it became clear that AYA long-term survivors were at increased risk for severe late effects. Moreover, limited information on long-term cancer impact is available for AYAs, since most studies focused on children and adolescents. We aimed to assess various long-term outcomes on AYA survivors of hematological cancers.MethodsWe selected patients diagnosed with a first primary hematological cancer between 1997 and 2006, in the Italian nationwide population-based cohort of AYA cancer survivors (i.e. alive at least 5 years after cancer diagnosis). Long-term outcomes of interest were: second malignant neoplasms (SMNs), hospitalizations and overall mortality. We calculated standardized incidence ratios (SIRs), standardized hospitalization rate ratios (SHRs) and standardized mortality rate ratios (SMRs). To study morbidity patterns over time, we modeled observed incidence rates by fitting flexible parametric models for nonlinear patterns and we used linear regression for linear patterns.ResultsThe study cohort included 5,042 AYA hematological cancer survivors of which 1,237 and 3,805 had a leukaemia and lymphoma diagnosis, respectively. AYA survivors were at substantially increased risk for SMN (SIR=2.1; 95%CI=1.7; 2.6), hospitalisation (SHR=1.5; 95%CI=1.5; 1.6), and mortality (SMR=1.4; 95%CI=1.2; 1.6) with differences between leukaemia and lymphoma survivors. The highest excess risks of hospitalisations were for infectious diseases, respiratory diseases, and diseases of blood and blood-forming organs. The morbidity pattern differs over time by morbidity type.ConclusionsOur results support the need for strict follow-up plans for survivors, and call for further study to better personalised follow-up plans for AYA cancer survivors.

A 49-year-old man with no significant past medical history received dexamethasone as part of his treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Less than 3 weeks later, the patient developed acute respiratory distress syndrome. Radiological and serological testing led to a diagnosis of acute hypoxic miliary coccidioidomycosis. A 52-year-old man with a past medical history of chronic kidney disease (CKD) was treated with prednisone for focal segmental glomerulosclerosis (FSGS). Within 2 weeks, this patient developed bilateral lower extremity weakness. Radiology, serology, and lumbar puncture proved a diagnosis of reactivated coccidioidomycosis with miliary pattern and coccidioidomycosis meningoencephalitis with arachnoiditis. Whether treatment with glucocorticoids caused reactivation of coccidioidomycosis is discussed in this case series.

Abstract Background We report our experience in managing iatrogenic renal bleedings after nephrostomic procedures by transarterial embolization using Micro Vascular Plug (MVP) (Medtronic, USA) as single or complementary embolization device with parenchimal sparing. Materials and methods Five patients have been treated in a single center with transarterial embolization because of renal hemorrhages occurring after positioning of nephrostomic drainages. All patients presented with back pain, severe hematuria and/or bright red blood into the nephrostomic bag, with fall in hemoglobin value. After contrast enhanced CT scan confirming arterial active bleeding, rescue embolization was performed using MVP. The renal parenchimal loss was estimated on final postembolization DSA. Creatinine values were monitored before and after the procedure. Results Technical and clinical successes were obtained in all patients. Two patients presented with extraluminal blush, one with multiple pseudoaneurysms, one with pseudoaneurysm with arterovenous fistula, one with extraluminal blush with arterovenous fistula. MVP models were choosen oversized because of vasospasm that would underestimate the effective caliber of target vessel; MVP 3Q and MVP 7Q were adopted in one patient each, while MVP 5Q was released in three cases. MVP was the sole embolizing agent in four patients; in one patient, MVP was employed after microcoils failed to obtain complete embolization. The percentage of renal parenchimal lost was lower than 20%; no increase in Creatinine values was detected at dismission. Conclusions According to proposed data, MVP seems to be a safe, effective and fast embolizing device that interventionalists could consider when facing renal bleedings, even as sole agent.

Type 1 diabetes (T1D) is a chronic autoimmune disease resulting in progressive destruction of β-cells. Several factors affecting lymphocyte and antigen-presenting cells, including dendritic cells (DCs), contribute to defective maintenance of tolerance in T1D. DC-10 are a subset of human DCs involved in IL-10-mediated tolerance. A precise monitoring of DC-10 in the peripheral blood is possible thanks to the discovery of specific biomarkers. DC-10, being cells that naturally express HLA-G, may be used for the appropriate staging of the disease. By enumerating and phenotypically characterizing DC-10 in the peripheral blood of subjects at different stages of T1D development—first-degree relatives (FDRs) of T1D patients, without (Abneg) or with (Abpos) autoantibodies, T1D patients at onset, and age-matched healthy controls (HCs)—we showed that DC-10 contain a high proportion of HLA-G-expressing cells as compared with monocytes. We reported that a low frequency of DC-10 during disease development is paralleled with the increased proportion of pro-inflammatory cDC2 cells. Moreover, DC-10 number and phenotype differ from Abneg FDRs, Abpos FDRs, and T1D patients compared with HCs, and DC-10 from T1D patients express low levels of CD83. Finally, multiple regression analysis, considering DC-10 and HLA-G-related parameters, showed that Abneg FDRs are more similar to subjects with autoimmunity than to HCs. This is the first demonstration that impairment in DC-10 number and phenotype, specifically CD83 expression, is associated with risk of developing T1D, suggesting a possible use of CD83+ DC-10 to stratify individuals at risk of T1D in conjunction with classical prognostic factors.

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.

Since late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) have become a worldwide threat to public health [...]

This paper deals with a UAV LiDAR methodological approach for the identification and extraction of archaeological features under canopy in hilly Mediterranean environments, characterized by complex topography and strong erosion. The presence of trees and undergrowth makes the reconnaissance of archaeological features and remains very difficult, while the erosion, increased by slope, tends to adversely affect the microtopographical features of potential archaeological interest, thus making them hardly identifiable. For the purpose of our investigations, a UAV LiDAR survey has been carried out at Perticara (located in Basilicata southern Italy), an abandoned medieval village located in a geologically fragile area, characterized by complex topography, strong erosion, and a dense forest cover. All of these characteristics pose serious challenge issues and make this site particularly significant and attractive for the setting and testing of an optimal LiDAR-based approach to analyze hilly forested regions searching for subtle archaeological features. The LiDAR based investigations were based on three steps: (i) field data acquisition and data pre-processing, (ii) data post-processing, and (iii) semi-automatic feature extraction method based on machine learning and local statistics. The results obtained from the LiDAR based analyses (successfully confirmed by the field survey) made it possible to identify the lost medieval village that represents an emblematic case of settlement abandoned during the crisis of the late Middle Ages that affected most regions in southern Italy.

Goji berries are widely known for their outstanding nutritional and medicinal properties; they are usually found in the market as dried fruit or as juice because the fruit has a short shelf-life, and little information is available about its postharvest behavior at low temperatures. This study aimed to determine the storage performance of goji berry fruit by evaluating physicochemical, and sensorial attributes during storage at three different temperatures (0, 5, and 7 °C) for 12 days in a range that has not been extensively studied before. In addition, fruit respiration and ethylene production rates were also measured at the three temperatures. Fruit stored at 0 °C showed the lowest respiration rate and ethylene production (5.8 mg CO2 kg−1h−1 and 0.7 µg C2H4 kg−1h−1, respectively); however, at this temperature, the incidence and severity of pitting and electrolytic leakage were the highest. In contrast, 5 °C was found to be the best storage temperature for goji berry fruit; the fruit appeared fresh and healthy, had the highest scores during sensory analysis with an acceptable general impression, and had the lowest amount of damage attributable to chilling injury, with 17.1% fruit presenting with shriveling, 12.5% pitting, 6.7% mold, and 35% electrolytic leakage on day 9 of storage. Storage of goji berries at 7 °C resulted in the lowest marketability and the highest incidence of decay. Significant differences were also found in the phytochemical attributes, vitamin C content, soluble solid content (SSC), titratable acidity (TA), SSC/TA ratio, total polyphenol content, 2,2-diphenylpicrylhydrazy (DPPH), and anthocyanin content. This study revealed that a storage temperature of 5 °C for 9 days is recommended to maintain the quality of fresh goji berry. Thus, broadening the existing knowledge of the postharvest behavior of fresh goji berries; our results can help improve the commercial life of goji berries and ensure high-quality attributes throughout distribution.

The pomegranate (Punica granatum L.), which contains high levels of health-promoting compounds, has received much attention in recent decades. Fruit storage potential ranges from 3 to 4 months in air and from 4 to 6 months in Controlled Atmospheres (CA) with 3–5% oxygen and 10–15% carbon dioxide. Storage life is limited by decay, chilling injury, weight loss (WL), and husk scald. In particular, husk scald (HS) limits pomegranate long-term storage at favorable temperatures. HS appears as skin browning which expands from stem end towards the blossom end during handling or long-term storage (10–12 weeks) at 6–10 °C. Even though HS symptoms are limited to external appearance, it may still significantly reduce pomegranate fruit marketability. A number of postharvest treatments have been proposed to prevent husk scald, including atmospheric modifications, intermittent warming, coatings, and exposure to 1-MCP. Long-term storage may induce phenolic compounds accumulation, affect organelles membranes, and activate browning enzymes such as polyphenol oxidases (PPO) and peroxidases (POD). Due to oxidation of tannins and phenolics, scalding becomes visible. There is no complete understanding of the etiology and biochemistry of HS. This review discusses the hypothesized mechanism of HS based on recent research, its association to postharvest treatments, and their possible targets.

Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is α-galactosidase A (α-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers.

Coastal erosion and its impacts on the involved communities is a topic of great scientific interest that also reflects the need for modern as well as cost and time-effective methodologies to be integrated into or even to substitute traditional investigation methods. The present study is based on an integrated approach that involves the use of data derived from UAV (Unmanned Aerial Vehicle) surveys. The study illustrates the long- to short-term shoreline evolution of the Molise coast (southern Italy) and then focuses on two selected beach stretches (Petacciato and Campomarino beaches), for which annual UAV surveys were performed from 2019 to 2021, to assess their most recent shoreline and morpho-topographical changes and related effects on their coastal vulnerability. UAV data were processed using the Structure from Motion (SfM) image processing tool. Along the beach profiles derived from the produced DEMs, the coastal vulnerability of the selected beach stretches was evaluated by using the Coastal Vulnerability Assessment (CVA) approach. The results obtained highlight some significant worsening of CVA indexes from 2019 to 2021, especially for the Campomarino beach, confirming the importance of the periodic updating of previous data. In conclusion, the easy use of the UAV technology and the good quality of the derived data make it an excellent approach for integration into traditional methodologies for the assessment of short-term shoreline and beach changes as well as for monitoring coastal vulnerability.

Activated PI3K-kinase Delta Syndrome (APDS) is an autosomal-dominant primary immunodeficiency (PID) caused by the constitutive activation of the PI3Kδ kinase. The consequent hyperactivation of the PI3K-Akt-mTOR pathway leads to an impaired T- and B-cells differentiation and function, causing progressive lymphopenia, hypogammaglobulinemia and hyper IgM. Patients with APDS show recurrent sinopulmonary and chronic herpes virus infections, immune dysregulation manifestations, including cytopenia, arthritis, inflammatory enteropathy, and a predisposition to persistent non-neoplastic splenomegaly/lymphoproliferation and lymphoma. The recurrence of the lymphoproliferative disorder and the difficulties in the proper definition of malignancy on histological examination represents the main challenge in the clinical management of APDS patients, since a prompt and correct diagnosis is needed to avoid major complications. Targeted therapies with PI3Kδ-Akt-mTOR pathway pharmacologic inhibitors (i.e., Rapamycin, Theophylline, PI3K inhibitors) represent a good therapeutic strategy. They can also be used as bridge therapies when HSCT is required in order to control refractory symptoms. Indeed, treated patients showed a good tolerance, improved immunologic phenotype and reduced incidence/severity of immune dysregulation manifestations. Here, we describe our experience in the management of four patients, one male affected with APDS1 (P1) and the other three, a male and two females, with APDS2 (P2, P3, P4) presenting with chronic EBV replication, recurrent episodes of immune dysregulation manifestations and lymphomas. These cases highlighted the importance of a tailored and close follow-up, including serial endoscopic and lymph nodes biopsies control to detect a prompt and correct diagnosis and offer the best therapeutic strategy.

Summary: Often when biological entities are measured in multiple ways, there are distinct categories of information: some information is easy-to-obtain information (EI) and can be gathered on virtually every subject of interest, while other information is hard-to-obtain information (HI) and can only be gathered on some. We propose building a model to make probabilistic predictions of HI using EI. Our feature mapping GAN (FMGAN), based on the conditional GAN framework, uses an embedding network to process conditions as part of the conditional GAN training to create manifold structure when it is not readily present in the conditions. We experiment on generating RNA sequencing of cell lines perturbed with a drug conditioned on the drug's chemical structure and generating FACS data from clinical monitoring variables on a cohort of COVID-19 patients, effectively describing their immune response in great detail. The bigger picture: Many experiments face a trade-off between gathering easy-to-collect information on many samples or hard-to-collect information on a smaller number of samples due to costs in terms of both money and time. We demonstrate that a mapping between the easy-to-collect and hard-to collect information can be trained as a conditional GAN from a subset of samples with both measured. With our conditional GAN model known as feature mapping GAN (FMGAN), the results of expensive experiments can be predicted, saving on the costs of actually performing the experiment. We study two example settings where this could have impact: pharmaceutical drug discovery, where early phase experiments require casting a wide net to find just a few potential leads to follow. FMGAN can also have a major impact in clinical setting, where standard measurements early in a stay can predict values of later single-cell-resolution samples.

Changes in climate, land use, and land management impact the occurrence and severity of wildland fires in many parts of the world. This is particularly evident in Europe, where ongoing changes in land use have strongly modified fire patterns over the last decades. Although satellite data by the European Forest Fire Information System provide large-scale wildland fire statistics across European countries, there is still a crucial need to collect and summarize in-depth local analysis and understanding of the wildland fire condition and associated challenges across Europe. This article aims to provide a general overview of the current wildland fire patterns and challenges as perceived by national representatives, supplemented by national fire statistics (2009–2018) across Europe. For each of the 31 countries included, we present a perspective authored by scientists or practitioners from each respective country, representing a wide range of disciplines and cultural backgrounds. The authors were selected from members of the COST Action “Fire and the Earth System: Science & Society” funded by the European Commission with the aim to share knowledge and improve communication about wildland fire. Where relevant, a brief overview of key studies, particular wildland fire challenges a country is facing, and an overview of notable recent fire events are also presented. Key perceived challenges included (1) the lack of consistent and detailed records for wildland fire events, within and across countries, (2) an increase in wildland fires that pose a risk to properties and human life due to high population densities and sprawl into forested regions, and (3) the view that, irrespective of changes in management, climate change is likely to increase the frequency and impact of wildland fires in the coming decades. Addressing challenge (1) will not only be valuable in advancing national and pan-European wildland fire management strategies, but also in evaluating perceptions (2) and (3) against more robust quantitative evidence.

Down syndrome (DS) patients prematurely show clinical manifestations usually associated with aging. Their immune system declines earlier than healthy individuals, leading to increased susceptibility to infections and higher incidence of autoimmune phenomena. Clinical features of accelerated aging indicate that trisomy 21 increases the biological age of tissues. Based on previous studies suggesting immune senescence in DS, we hypothesized that induction of cellular senescence may contribute to early thymic involution and immune dysregulation. Immunohistochemical analysis of thymic tissue showed signs of accelerated thymic aging in DS patients, normally seen in older healthy subjects. Moreover, our whole transcriptomic analysis on human Epcam-enriched thymic epithelial cells (hTEC), isolated from three DS children, which revealed disease-specific transcriptomic alterations. Gene set enrichment analysis (GSEA) of DS TEC revealed an enrichment in genes involved in cellular response to stress, epigenetic histone DNA modifications and senescence. Analysis of senescent markers and oxidative stress in hTEC and thymocytes confirmed these findings. We detected senescence features in DS TEC, thymocytes and peripheral T cells, such as increased β-galactosidase activity, increased levels of the cell cycle inhibitor p16, telomere length and integrity markers and increased levels of reactive oxygen species (ROS), all factors contributing to cellular damage. In conclusion, our findings support the key role of cellular senescence in the pathogenesis of immune defect in DS while adding new players, such as epigenetic regulation and increased oxidative stress, to the pathogenesis of immune dysregulation.

Albeit the pathogenesis of COVID-19 remains unclear, host’s genetic polymorphisms in genes involved in infection and reinfection, inflammation, or immune stimulation could play a role in determining the course and outcome. We studied in the early phase of pandemic consecutive patients (N = 383) with SARS-CoV-2 infection, whose subsequent clinical course was classified as mild or severe, the latter being characterized by admission to intensive therapy unit or death. Five host gene polymorphisms (MERTK rs4374383, PNPLA3 rs738409, TLL-1 rs17047200, IFNL3 rs1297860, and INFL4 rs368234815) were assessed by using whole nucleic acids extracted from nasopharyngeal swabs. Specific protease cleavage sites of TLL-1 on the SARS-CoV-2 Spike protein were predicted in silico. Male subjects and older patients were significantly at higher risk for a severe outcome (p = 0.02 and p < 0.001, respectively). By considering patients ≤65 years, after adjusting for potential confounding due to sex, an increased risk of severe outcome was found in subjects with the GG genotype of PNPLA3 (adj-OR: 4.69; 95% CI = 1.01–22.04) or TT genotype of TLL-1 (adj-OR=9.1; 95% CI = 1.45–57.3). In silico evaluation showed that TLL-1 is potentially involved in the Spike protein cleavage which is essential for viral binding and entry into the host cells using the host receptor angiotensin-converting enzyme 2 (ACE2). Subjects carrying a GG genotype in PNPLA3 gene might have a constitutive upregulation of the NLRP3 inflammasome and be more prone to tissue damage when infected by SARS-CoV-2. The TT genotype in TLL-1 gene might affect its protease activity on the SARS-CoV-2 Spike protein, enhancing the ability to infect or re-infect host’s cells. The untoward effect of these variants on disease course is evident in younger patients due to the relative absence of comorbidities as determinants of prognosis. In the unresolved pathogenetic scenery of COVID-19, the identification of genetic variants associates with more prolonged course or with a severe outcome of infection would support the development of predictive tools useful to stratify subjects by risk class at presentation. Moreover, the individuation of key genes could contribute to a better understanding of the pathways involved in the pathogenesis, giving the basis for rational therapeutic approaches.

In the last decades, the endoplasmic reticulum (ER) has emerged as a key coordinator of cellular homeostasis, thanks to its physical interconnection to almost all intracellular organelles. In particular, an intense and mutual crosstalk between the ER and mitochondria occurs at the mitochondria–ER contacts (MERCs). MERCs ensure a fine-tuned regulation of fundamental cellular processes, involving cell fate decision, mitochondria dynamics, metabolism, and proteostasis, which plays a pivotal role in the tumorigenesis and therapeutic response of cancer cells. Intriguingly, recent studies have shown that different components of the unfolded protein response (UPR) machinery, including PERK, IRE1α, and ER chaperones, localize at MERCs. These proteins appear to exhibit multifaceted roles that expand beyond protein folding and UPR transduction and are often related to the control of calcium fluxes to the mitochondria, thus acquiring relevance to cell survival and death. In this review, we highlight the novel functions played by PERK, IRE1α, and ER chaperones at MERCs focusing on their impact on tumor development.

Invariant Natural Killer T (iNKT) cells are a small and distinct population of T cells crucial in immunomodulation. After activation by alpha-GalactosylCeramide (αGC), an exogenic glycolipid antigen, iNKT cells can rapidly release cytokines to enhance specific anti-tumor activity. Several human clinical trials on iNKT cell-based anti-cancer are ongoing, however results are not as striking as in murine models. Given that iNKT-based immunotherapies are dependent mainly on antigen-presenting cells (APC), a human tolerogenic molecule with no murine homolog, such as Human Leucocyte Antigen G (HLA-G), could contribute to this discrepancy. HLA-G is a well-known immune checkpoint molecule involved in fetal-maternal tolerance and in tumor immune escape. HLA-G exerts its immunomodulatory functions through the interaction with immune inhibitory receptors such as ILT2, differentially expressed on immune cell subsets. We hypothesized that HLA-G might inhibit iNKT function directly or by inducing tolerogenic APC leading to iNKT cell anergy, which could impact the results of current clinical trials. Using an ILT2-transduced murine iNKT cell line and human iNKT cells, we demonstrate that iNKT cells are sensitive to HLA-G, which inhibits their cytokine secretion. Furthermore, human HLA-G+ dendritic cells, called DC-10, failed at inducing iNKT cell activation compared to their autologous HLA-G‒ DCs counterparts. Our data show for the first time that the HLA-G/ILT2 ICP is involved in iNKT cell function modulation.

Multiple myeloma (MM) is an incurable malignancy of plasma cells that grow within a permissive bone marrow microenvironment (BMM). The bone marrow milieu supports the malignant transformation both by promoting uncontrolled proliferation and resistance to cell death in MM cells, and by hampering the immune response against the tumor clone. Hence, it is expected that restoring host anti-MM immunity may provide therapeutic benefit for MM patients. Already several immunotherapeutic approaches have shown promising results in the clinical setting. In this review, we outline recent findings demonstrating the potential advantages of targeting the immunosuppressive bone marrow niche to restore effective anti-MM immunity. We discuss different approaches aiming to boost the effector function of T cells and/or exploit innate or adaptive immunity, and highlight novel therapeutic opportunities to increase the immunogenicity of the MM clone. We also discuss the main challenges that hamper the efficacy of immune-based approaches, including intrinsic resistance of MM cells to activated immune-effectors, as well as the protective role of the immune-suppressive and inflammatory bone marrow milieu. Targeting mechanisms to convert the immunologically “cold” to “hot” MM BMM may induce durable immune responses, which in turn may result in long-lasting clinical benefit, even in patient subgroups with high-risk features and poor survival.

We present a 14-year-old boy with peritoneal epithelial malignant mesothelioma (PEMM). While pathology is required to make this diagnosis, radiology plays a crucial role throughout the clinical course of this disease. The key imaging characteristics of peritoneal mesothelioma have been previously well-described in the adult population, but there are rare reports in the pediatric population. This pediatric report highlights the multidimensional use of imaging in this disease, from the initial evaluation to therapeutic supplementation and subsequent follow-up.

This study examined factors that predicted children's gender intergroup attitudes at age 5 and the implications of these attitudes for intergroup behavior. Ethnically diverse children from low-income backgrounds (N = 246; Mexican-, Chinese-, Dominican-, and African American) were assessed at ages 4 and 5. On average, children reported positive same-gender and negative other-gender attitudes. Positive same-gender attitudes were associated with knowledge of gender stereotypes. In contrast, positive other-gender attitudes were associated with flexibility in gender cognitions (stereotype flexibility, gender consistency). Other-gender attitudes predicted gender-biased behavior. These patterns were observed in all ethnic groups. These findings suggest that early learning about gender categories shape young children's gender attitudes and that these gender attitudes already have consequences for children's intergroup behavior at age 5.

In recent years, the efficient numerical solution of Hamiltonian problems has led to the definition of a class of energy-conserving Runge–Kutta methods named Hamiltonian Boundary Value Methods (HBVMs). Such methods admit an interesting interpretation in terms of continuous-stage Runge–Kutta methods. In this review paper, we recall this aspect and extend it to higher-order differential problems.