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Summary: Background: Oral tauroursodeoxycholic acid (TUDCA) is a commercial drug currently tested in patients with amyotrophic lateral sclerosis (ALS) both singly and combined with sodium phenylbutyrate. This retrospective study aimed to investigate, in a real-world setting, whether TUDCA had an impact on the overall survival of patients with ALS who were treated with this drug compared to those patients who received standard care only. Methods: This propensity score–matched study was conducted in the Emilia Romagna Region (Italy), which has had an ALS regional registry since 2009. Out of 627 patients with ALS diagnosed from January 1st, 2015 to June 30th, 2021 and recorded in the registry with available information on death/tracheostomy, 86 patients took TUDCA and were matched in a 1:2 ratio with patients who received only usual care according to age at onset, sex, phenotype, diagnostic latency, ALS Functional Rating Scale-Revised (ALSFRS-R) at first visit, disease progression rate at first visit, and BMI at diagnosis. The primary outcome was survival difference (time from onset of symptoms to tracheostomy/death) between TUDCA exposed and unexposed patients. Findings: A total of 86 patients treated with TUDCA were matched to 172 patients who did not receive treatment. TUDCA-exposed patients were stratified based on dosage (less than or equal to 1000 mg/day or greater) and duration (less than or equal to 12 months or longer) of treatment. The median overall survival was 49.6 months (95% CI 41.7–93.5) among those treated with TUDCA and 36.2 months (95% CI 32.7–41.6) in the control group, with a reduced risk of death observed in patients exposed to a higher dosage (defined as ≥ 1000 mg/day) of TUDCA (HR 0.56; 95% CI 0.38–0.83; p = 0.0042) compared to both the control group and those with lower TUDCA dosages (defined as

Abstract To achieve sustainable development worldwide, the United Nations set 17 Sustainable Development Goals (SDGs) for humanity to reach by 2030. Society is involved in the challenge, with firms playing a crucial role. Thus, a key question is to what extent firms engage with the SDGs. Efforts to map firms’ contributions have mainly focused on analysing companies’ reports based on limited samples and non-real-time data. We present a novel interdisciplinary approach based on analysing big data from an online social network (Twitter) with complex network methods from statistical physics. By doing so, we provide a comprehensive and nearly real-time picture of firms’ engagement with SDGs. Results show that: (1) SDGs themes tie conversations among major UK firms together; (2) the social dimension is predominant; (3) the attention to different SDGs themes varies depending on the community and sector firms belong to; (4) stakeholder engagement is higher on posts related to global challenges compared to general ones; (5) large UK companies and stakeholders generally behave differently from Italian ones. This paper provides theoretical contributions and practical implications relevant to firms, policymakers and management education. Most importantly, it provides a novel tool and a set of keywords to monitor the influence of the private sector on the implementation of the 2030 Agenda.

Vibration analysis of wing-box structures is a crucial aspect of the aeronautic design to avoid aeroelastic effects during normal flight operations. The deformation of a wing structure can induce nonlinear couplings, causing a different dynamic behavior from the linear counterpart, and nonlinear effects should be considered for more realistic simulations. Moreover, composite materials and aeroelastic tailoring require new simulation tools to include bending–torsion coupling effects. In this research, a beam finite element with bending–torsion coupling formulation is used to investigate the effects of the deflection of beam structures with different aspect ratios. The nonlinear effects are included in the finite element formulation. The geometrical effect is considered, applying a deformation dependent transformation matrix. Stiffness effects are introduced in the stiffness matrix with Hamilton’s Principle and a perturbation approach. The results obtained with the beam finite element model are compared with numerical and experimental evidence.

Torquetenovirus (TTV) is a negative sense, single-stranded DNA virus present in many body fluids of apparently healthy individuals. At present, it is considered a non-pathogenic endogenous virus. TTV can be detected in the vagina of pregnant women, its abundance being modulated with the extent of immune system activation. Until now, there is only scarce information regarding the association between TTV and the composition of the vaginal environment. Therefore, this study aimed to assess the presence of TTV in the vaginal ecosystem of a cohort of white women with a normal pregnancy (n = 60) at different gestational stages (first, second and third trimester) and in 9 subjects suffering a first trimester miscarriage. For each woman, we determined (i) the presence and titer of TTV, (ii) the vaginal bacterial composition by means of Nugent score and 16S rRNA gene sequencing, (iii) the vaginal metabolic profiles through 1H-NMR spectroscopy, and (iv) the vaginal concentration of two pro-inflammatory cytokines (IL-6 and IL-8). More than one third of women were found negative for TTV at all gestational stages. Although not statistically significant, the positivity for TTV dropped from 53.3% in the first to 36.6% in the third trimester. TTV loads varied greatly among vaginal samples, ranging between 2 × 101 and 2 × 105 copies/reaction. No difference in TTV prevalence and loads was observed between women with normal pregnancies and miscarriages. The presence of TTV was more common in women with a higher vaginal leucocyte count (p = 0.02). The levels of IL-6 (p = 0.02), IL-8 (p = 0.03), propionate (p = 0.001) and cadaverine (p = 0.006) were significantly higher in TTV-positive samples. TTV titer was positively correlated with the concentrations of 4-hydroxyphenyllactate (p < 0.0001), isoleucine (p = 0.01) and phenylalanine (p = 0.04). TTV-positive samples were characterized by a higher relative abundance of Sneathia (p = 0.04) and Shuttleworthia (p = 0.0009). In addition, a trend toward a decrease of Lactobacillus crispatus and Lactobacillus jensenii, and an increase of Lactobacillus iners was observed for TTV-positive samples. In conclusion, we found that TTV is quite common in women with normal pregnancy outcomes, representing a possible predictor of local immune status.

Acute myeloid leukemia (AML) is an aggressive hematologic neoplasia with a complex polyclonal architecture. Among driver lesions, those involving the FLT3 gene represent the most frequent mutations identified at diagnosis. The development of tyrosine kinase inhibitors (TKIs) has improved the clinical outcomes of FLT3-mutated patients (Pt). However, overcoming resistance to these drugs remains a challenge. To unravel the molecular mechanisms underlying therapy resistance and clonal selection, we conducted a longitudinal analysis using a single-cell DNA sequencing approach (MissionBioTapestri® platform, San Francisco, CA, USA) in two patients with FLT3-mutated AML. To this end, samples were collected at the time of diagnosis, during TKI therapy, and at relapse or complete remission. For Pt #1, disease resistance was associated with clonal expansion of minor clones, and 2nd line TKI therapy with gilteritinib provided a proliferative advantage to the clones carrying NRAS and KIT mutations, thereby responsible for relapse. In Pt #2, clonal architecture was less complex, and 1st line TKI therapy with midostaurin was able to eradicate the leukemic clones. Our results corroborate previous findings about clonal selection driven by TKIs, highlighting the importance of a deeper characterization of individual clonal architectures for choosing the best treatment plan for personalized approaches aimed at optimizing outcomes. [ABSTRACT FROM AUTHOR]

A deep comprehension of the vaginal ecosystem may hold promise for unraveling the pathophysiology of pregnancy and may provide novel biomarkers to identify subjects at risk of maternal-fetal complications. In this prospective study, we assessed the characteristics of the vaginal environment in a cohort of pregnant women throughout their different gestational ages and puerperium. Both the vaginal bacterial composition and the vaginal metabolic profiles were analyzed. A total of 63 Caucasian women with a successful pregnancy and 9 subjects who had a first trimester miscarriage were enrolled. For the study, obstetric examinations were scheduled along the three trimester phases (9-13, 20-24, 32-34 gestation weeks) and puerperium (40-55 days after delivery). Two vaginal swabs were collected at each time point, to assess the vaginal microbiome profiling (by Nugent score and 16S rRNA gene sequencing) and the vaginal metabolic composition (1H-NMR spectroscopy). During pregnancy, the vaginal microbiome underwent marked changes, with a significant decrease in overall diversity, and increased stability. Over time, we found a significant increase of Lactobacillus and a decrease of several genera related to bacterial vaginosis (BV), such as Prevotella, Atopobium and Sneathia. It is worth noting that the levels of Bifidobacterium spp. tended to decrease at the end of pregnancy. At the puerperium, a significantly lower content of Lactobacillus and higher levels of Gardnerella, Prevotella, Atopobium, and Streptococcus were observed. Women receiving an intrapartum antibiotic prophylaxis for Group B Streptococcus (GBS) were characterized by a vaginal abundance of Prevotella compared to untreated women. Analysis of bacterial relative abundances highlighted an increased abundance of Fusobacterium in women suffering a first trimester abortion, at all taxonomic levels. Lactobacillus abundance was strongly correlated with higher levels of lactate, sarcosine, and many amino acids (i.e., isoleucine, leucine, phenylalanine, valine, threonine, tryptophan). Conversely, BV-associated genera, such as Gardnerella, Atopobium, and Sneathia, were related to amines (e.g., putrescine, methylamine), formate, acetate, alcohols, and short-chain fatty-acids (i.e., butyrate, propionate).

Few studies have focused on elderly (>80 years) amyotrophic lateral sclerosis (ALS) patients, who represent a fragile subgroup generally not included in clinical trials and often neglected because they are more difficult to diagnose and manage. We analyzed the clinical and genetic features of very late-onset ALS patients through a prospective, population-based study in the Emilia Romagna Region of Italy. From 2009 to 2019, 222 (13.76%) out of 1613 patients in incident cases were over 80 years old at diagnosis, with a female predominance (F:M = 1.18). Elderly ALS patients represented 12.02% of patients before 2015 and 15.91% from 2015 onwards (p = 0.024). This group presented with bulbar onset in 38.29% of cases and had worse clinical conditions at diagnosis compared to younger patients, with a lower average BMI (23.12 vs. 24.57 Kg/m2), a higher progression rate (1.43 vs. 0.95 points/month), and a shorter length of survival (a median of 20.77 vs. 36 months). For this subgroup, genetic analyses have seldom been carried out (25% vs. 39.11%) and are generally negative. Finally, elderly patients underwent less frequent nutritional- and respiratory-supporting procedures, and multidisciplinary teams were less involved at follow-up, except for specialist palliative care. The genotypic and phenotypic features of elderly ALS patients could help identify the different environmental and genetic risk factors that determine the age at which disease onset occurs. Since multidisciplinary management can improve a patient’s prognosis, it should be more extensively applied to this fragile group of patients.

This research presents a new beam finite element capable of predicting static and dynamic behavior of beam structures with bending-torsion coupling. The model here derived establishes a relation between the bending and torsional nodal degree of freedom of a two node beam element. The equilibrium equations are derived neglecting the non-linear terms while the stiffness and mass matrices are derived with Galerkin’s method. The shape functions are obtained considering Timoshenko’s hypothesis and the torsional moment constant along the element. The model has been validated through numerical and experimental results for static and dynamic simulation. The comparison revealed a relative difference mostly lower than 5% for static deformations and natural frequency prediction, while the Modal Assurance Criterion (MAC) confirmed the consistency with numerical and experimental results in terms of mode shape similarity.

Gardnerella vaginalis (GV) is an anaerobic bacterial species involved in the pathogenesis of bacterial vaginosis (BV), a condition of vaginal dysbiosis associated with adverse pregnancy outcomes. GV strains are categorized into four clades, characterized by a different ability to produce virulence factors, such as sialidase. We investigated the distribution of GV clades and sialidase genes in the vaginal ecosystem of a cohort of pregnant women, assessing the correlations between GV clades and the whole vaginal microbiome. A total of 61 Caucasian pregnant women were enrolled. Their vaginal swabs, collected both at the first and third trimester of pregnancy, were used for (i) evaluation of the vaginal status by Nugent score, (ii) vaginal microbiome profiling by 16S rRNA sequencing, (iii) detection and quantification of GV clades and sialidase A gene by qPCR assays. DNA of at least one GV clade was detected in most vaginal swabs, with clade 4 being the most common one. GV clade 2, together with the presence of multiple clades (>2 simultaneously), were significantly associated with a BV condition. Significantly higher GV loads and sialidase gene levels were found in BV cases, compared to the healthy status. Clade 2 was related to the major shifts in the vaginal microbial composition, with a decrease in Lactobacillus and an increase in several BV-related taxa. As the number of GV clades detected simultaneously increased, a group of BV-associated bacteria tended to increase as well, while Bifidobacterium tended to decrease. A negative correlation between sialidase gene levels and Lactobacillus, and a positive correlation with Gardnerella, Atopobium, Prevotella, Megasphaera, and Sneathia were observed. Our results added knowledge about the interactions of GV clades with the inhabitants of the vaginal microbiome, possibly helping to predict the severity of BV and opening new perspectives for the prevention of pregnancy-related complications.

FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations of the FLT3 receptor include internal tandem duplications (ITD) that map to the auto-inhibitory juxtamembrane (JM) domain or point mutations within the tyrosine kinase domain (TKD). Several FLT3 tyrosine kinase inhibitors have been developed in the last few years, but midostaurin is currently the only one approved for the treatment of newly diagnosed patients harboring FLT3 mutations. Here we describe for the first time a novel in-frame deletion in exon 14 (JM domain) of the FLT3 gene, that we identified in a young woman with CBFb-MYH11-positive AML. We demonstrated that this novel FLT3 variant is pathogenic, since it is responsible for constitutive activation of FLT3 receptor. Finally, ex-vivo studies demonstrated that this novel mutation is sensitive to midostaurin.

Vaginal microbes and their metabolic products have crucial functions, affecting local immunity development and maternal-fetal health. The composition of the vaginal microbiome can vary in response to various factors, including body mass index (BMI), and diet. In this study we get new insights into the vaginal ecosystem of Caucasian women (n = 24) at the first trimester of pregnancy, assessing whether pre-pregnancy diet can affect the structure of the vaginal environment in terms of bacterial composition and vaginal metabolite concentration. We characterized 1) the vaginal bacterial composition (Nugent score), 2) the vaginal metabolic profiles (1H-NMR spectroscopy), and 3) the dietary nutrient intake by means of a validated food frequency questionnaire. Pre-pregnancy BMI was negatively related to vaginal health status, indicating that women who begin pregnancy overweight/obese have a greater occurrence of vaginal dysbiosis during pregnancy. A lactobacilli-dominated vaginal microbiota was negatively associated with higher pre-pregnancy intake of animal-sourced protein. Conversely, a higher pre-pregnancy consumption of total carbohydrates and sugars seemed to be a protective factor for vaginal health. The vaginal environment of BV-women was characterized by higher levels of biogenic amines and organic acids, whereas higher levels of phenylpropionate and diverse amino acids were fingerprints of a healthy vaginal status. A significant association between a higher pre-pregnancy BMI and several dysbiosis-related vaginal metabolites was also found. Our study shed light on the role of pre-pregnancy BMI and diet on the vaginal environment during pregnancy, underlining the importance of limiting protein intake from animal foods to maintain a healthy lactobacilli-dominated microbiota.

During pregnancy, the vaginal ecosystem undergoes marked changes, including a significant enrichment with Lactobacillus spp. and profound alterations in metabolic profiles. A deep comprehension of the vaginal environment may shed light on the physiology of pregnancy and may provide novel biomarkers to identify subjects at risk of complications (e.g., miscarriage, preterm birth). In this study, we characterized the vaginal ecosystem in Caucasian women with a normal pregnancy (n = 64) at three different gestational ages (i.e., first, second and third trimester) and in subjects (n = 10) suffering a spontaneous first trimester miscarriage. We assessed the vaginal bacterial composition (Nugent score), the vaginal metabolic profiles (1H-NMR spectroscopy) and the vaginal levels of two cytokines (IL-6 and IL-8). Throughout pregnancy, the vaginal microbiota became less diverse, being mainly dominated by lactobacilli. This shift was clearly associated with marked changes in the vaginal metabolome: over the weeks, a progressive reduction in the levels of dysbiosis-associated metabolites (e.g., biogenic amines, alcohols, propionate, acetate) was observed. At the same time, several metabolites, typically found in healthy vaginal conditions, reached the highest concentrations at the end of pregnancy (e.g., lactate, glycine, phenylalanine, leucine, isoleucine). Lower levels of glucose were an additional fingerprint of a normal vaginal environment. The vaginal levels of IL-6 and IL-8 were significantly associated with the number of vaginal leukocytes, as well as with the presence of vaginal symptoms, but not with a condition of dysbiosis. Moreover, IL-8 concentration seemed to be a good predictor of the presence of vaginal Candida spp. Cytokine concentrations were negatively correlated to lactate, serine, and glycine concentrations, whereas the levels of 4-hydroxyphenyllactate, glucose, O-acetylcholine, and choline were positively correlated with Candida vaginal loads. Finally, we found that most cases of spontaneous abortion were associated with an abnormal vaginal microbiome, with higher levels of selected metabolites in the vaginal environment (e.g., inosine, fumarate, xanthine, benzoate, ascorbate). No association with higher pro-inflammatory cytokines was found. In conclusion, our analysis provides new insights into the pathophysiology of pregnancy and highlights potential biomarkers to enable the diagnosis of early pregnancy loss.

This paper offers insights on the major issues and challenges firms face in the Covid-19 pandemic and their concerns for Corporate Social Responsibility (CSR) themes. To do so, we investigate large Italian firms' discussions on Twitter in the first nine months of the pandemic. Specifically, we ask: How is firms' Twitter discussion developing during the Covid-19 pandemic? Which CSR dimensions and topics do firms discuss? To what extent do they resonate with the public? We downloaded Twitter posts by the accounts of large Italian firms, and we built the bipartite network of accounts and hashtags. Using an entropy-based null model as a benchmark, we projected the information contained in the network into the accounts layers, identifying a network of accounts. We find that the network is composed of 13 communities and accounts at the core of the network focus on environmental sustainability, digital innovation, and safety. Firms' ownership type does not seem to influence the conversation. While the relevance of CSR hashtags and stakeholder engagement is relatively small, peculiarities arise in some communities. Overall, our paper highlights the contribution of online social networks and complex networks methods for management and strategy research, showing the role of online social media in understanding firms' issues, challenges, and responsibilities, with common narratives naturally emerging from data.

During pregnancy, the vaginal microbiome plays an important role in both maternal and neonatal health outcomes. Throughout pregnancy, the vaginal microbial composition undergoes significant changes, including a decrease in overall diversity and enrichment with Lactobacillus spp. In turn, the modifications in the microbial profiles are associated with shifts in the composition of vaginal metabolites. In this study, we characterized the vaginal metabolic profiles throughout pregnancy at two different gestational ages, correlating them with a microscopic evaluation of the vaginal bacterial composition. A total of 67 Caucasian pregnant women presenting to the Family Advisory Health Centres of Ravenna (Italy) were enrolled and a vaginal swab was collected at gestational ages 9-13 weeks (first trimester) and 20-24 weeks (second trimester). The composition of the vaginal microbiome was assessed by Nugent score and women were divided in 'H' (normal lactobacilli-dominated microbiota), 'I' (intermediate microbiota), and 'BV' (bacterial vaginosis) groups. Starting from the cell-free supernatants of the vaginal swabs, a metabolomic analysis was performed by means of a 1H-NMR spectroscopy. From the first to the second trimester, a greater number of women showed a normal lactobacilli-dominated microbiota, with a reduction of cases of dysbiosis. These microbial shifts were associated with profound changes in the vaginal metabolic profiles. Over the weeks, a significant reduction in the levels of BV-associated metabolites (e.g. acetate, propionate, tyramine, methylamine, putrescine) was observed. At the same time, the vaginal metabolome was characterized by higher concentrations of lactate and of several amino acids (e.g. tryptophan, threonine, isoleucine, leucine), typically found in healthy vaginal conditions. Over time, the vaginal metabolome became less diverse and more homogeneous: in the second trimester, women with BV showed metabolic profiles more similar to the healthy/intermediate groups, compared to the first trimester. Our data could help unravel the role of vaginal metabolites in the pathophysiology of pregnancy.

Increased incidence rates of amyotrophic lateral sclerosis (ALS) have been recently reported across various Western countries, although geographic and temporal variations in terms of incidence, clinical features and genetics are not fully elucidated. This study aimed to describe demographic, clinical feature and genotype–phenotype correlations of ALS cases over the last decade in the Emilia Romagna Region (ERR). From 2009 to 2019, our prospective population-based registry of ALS in the ERR of Northern Italy recorded 1613 patients receiving a diagnosis of ALS. The age- and sex-adjusted incidence rate was 3.13/100,000 population (M/F ratio: 1.21). The mean age at onset was 67.01 years; women, bulbar and respiratory phenotypes were associated with an older age, while C9orf72-mutated patients were generally younger. After peaking at 70–75 years, incidence rates, among women only, showed a bimodal distribution with a second slight increase after reaching 90 years of age. Familial cases comprised 12%, of which one quarter could be attributed to an ALS-related mutation. More than 70% of C9orf72-expanded patients had a family history of ALS/fronto-temporal dementia (FTD); 22.58% of patients with FTD at diagnosis had C9orf72 expansion (OR 6.34, p = 0.004). In addition to a high ALS incidence suggesting exhaustiveness of case ascertainment, this study highlights interesting phenotype–genotype correlations in the ALS population of ERR.

Vibration analysis of wing-box structures is a crucial aspect of the aeronautic design to avoid aeroelastic effects during normal flight operations. The deformation of a wing structure can induce nonlinear couplings, causing a different dynamic behavior from the linear counterpart, and nonlinear effects should be considered for more realistic simulations. Moreover, composite materials and aeroelastic tailoring require new simulation tools to include bending–torsion coupling effects. In this research, a beam finite element with bending–torsion coupling formulation is used to investigate the effects of the deflection of beam structures with different aspect ratios. The nonlinear effects are included in the finite element formulation. The geometrical effect is considered, applying a deformation dependent transformation matrix. Stiffness effects are introduced in the stiffness matrix with Hamilton's Principle and a perturbation approach. The results obtained with the beam finite element model are compared with numerical and experimental evidence. [ABSTRACT FROM AUTHOR]

The inhabitants of the vaginal ecosystem can harbor genetic determinants conferring antimicrobial resistance. However, detailed data about the distribution of resistance genes in the vaginal microbiome of pregnant women are still lacking. Therefore, we assessed the presence of macrolide (i.e., erm genes) and tetracycline (i.e., tet genes) resistance markers in the vaginal environment of Caucasian women at different gestational ages. Furthermore, the detection of resistance genes was related to the composition of the vaginal microbiota. A total of 228 vaginal samples, collected at different trimesters of pregnancy or during the puerperium, were tested for the presence of ermB, ermF, tet(W), and tet(M) by in-house end-point PCR assays. The composition of the vaginal microbiota was assessed through a microscopic evaluation (i.e., Nugent score) and by means of sequencing V3–V4 hypervariable regions of the bacterial 16 rRNA gene. Overall, the most detected resistance gene was tet(M) (76.7%), followed by ermB (55.2%). In 17% of women, mainly with a ‘normal’ vaginal microbiota, no resistance genes were found. Except for tet(W), a significant correlation between the positivity of resistance genes and a dysbiotic vaginal status (i.e., bacterial vaginosis (BV)) was noticed. Indeed, samples positive for at least one resistance determinant were characterized by a decrease in Lactobacillus spp. and an increase of BV-related genera (Prevotella, Gardnerella, Atopobium, Sneathia). A high predominance of vaginal Lactobacillus spp. (>85%) was associated with a lower risk of tet(W) gene detection, whereas the presence of Megasphaera (>1%) increased the risk of positivity for all analyzed genes. Different types of vaginal microbiota are associated with peculiar resistance profiles, being a lactobacilli-dominated ecosystem poor in or free of resistance genes. These data could open new perspectives for promoting maternal and neonatal health.

Chile es uno de los países OCDE que exhibe mayor grado de segregación socioeconómica en su sistema escolar. Esto se explicaría por la incidencia de tres factores: institucionales (como los cobros y procesos de selección de estudiantes por parte de las escuelas), socioculturales (valoraciones y comportamientos de las familias frente a la elección de escuela) y de contexto, entre los que la segrega - ción residencial aparece como el más relevante. Este trabajo analiza la relación entre localización de las escuelas, composición socioeconómica del alumnado y pro - cedencia (movilidad) del mismo. La información utilizada proviene de 1 631 encuestas a familias de alumnos de ense - ñanza primaria. Los resultados evidencian que la segregación residencial influye sólo parcialmente sobre la segregación socioeconómica escolar porque la capacidad de movilización es un factor determinante para “romper” la asociación entre ambos fenómenos. La segregación residencial afectaría en mayor medida a estudiantes de nivel socioeconómico bajo que asisten a escuelas en las inmediaciones de sus hogares, recorriendo distancias menores que niños de niveles socioe - conómicos superiores quienes tienden a movilizarse más entre casa y escuela. Sin embargo, el análisis comparativo de los casos complejiza esa conclusión, porque estudiantes del mismo nivel socioeconómico pueden recorrer diferentes distancias. Las características de los territorios donde se loca - lizan las escuelas parecen tener relación con tales diferencias. A partir de los resultados del estudio se plantea rediscutir el uso del concepto de segregación residencial para explicar fenómenos como la segregación escolar dada la compleji - dad de las interrelaciones entre procesos de fragmentación territorial y movilidad cotidiana.

Summary: NPM1‐mutated acute myeloid leukaemia (NPM1mut AML) represents a mostly favourable/intermediate risk disease that benefits from allogeneic haematopoietic stem cell transplantation (HSCT) in case of measurable residual disease (MRD) relapse or persistence after induction chemotherapy. Although the negative prognostic role of pre‐HSCT MRD is established, no recommendations are available for the management of peri‐transplant molecular failure (MF). Based on the efficacy data of venetoclax (VEN)‐based treatment in NPM1mut AML older patients, we retrospectively analysed the off‐label combination of VEN plus azacitidine (AZA) as bridge‐to‐transplant strategy in 11 NPM1mut MRD‐positive fit AML patients. Patients were in MRD‐positive complete remission (CRMRDpos) at the time of treatment: nine in molecular relapse and two in molecular persistence. After a median number of two cycles (range 1–4) of VEN–AZA, 9/11 (81.8%) achieved CRMRD‐negative (CRMRDneg). All 11 patients proceeded to HSCT. With a median follow‐up from treatment start of 26 months, and a median post‐HSCT follow‐up of 19 months, 10/11 patients are alive (1 died from non‐relapse mortality), and 9/10 patients are in MRDneg status. This patient series highlights the efficacy and safety of VEN–AZA to prevent overt relapse, achieve deep responses and preserve patient fitness before HSCT, in patients with NPM1mut AML in MF. [ABSTRACT FROM AUTHOR]

Dimensional accuracy of selective laser melting (SLM) parts is one of manufacturers' major concerns. The additive manufacturing (AM) process is characterized by high-temperature gradients, consolidation, and thermal expansion, which induce residual stress on the part. These stresses are released by separating the part from the baseplate, leading to plastic deformation. Thermo-mechanical finite elements (FE) simulation can be adopted to determine the effect of process parameters on final geometrical accuracy and minimize non-compliant parts. In this research, a geometry for process parameter calibration is presented. The part has been manufactured and then analyzed with industrial computed tomography (iCT). An FE process simulation has been performed considering material removal during base plate separation, and the computed distortions have been compared with the results of the iCT, revealing good accordance between the final product and its digital twin. [ABSTRACT FROM AUTHOR]

This research presents the application of a beam finite element, specifically derived for simulating bending–torsion coupling in equivalent box-beam structures with curvilinear stiffeners. The stiffener path was simulated and optimized to obtain an expected coupling effect with respect to four typical static load cases, including geometric constraints related to the additive manufacturing production method. The selected load condition was applied to the centroid of the beam section, and the structure performance was consequently determined. A variation in load position up to one-fourth of the beam width was considered for investigating the stiffener path variation corresponding to a minimum bending–torsion coupling effect. The results demonstrated the capability of such a beam finite element to correctly represent the static behavior of beam structures with curvilinear stiffeners and show the possibility to uncouple its bending–torsion behavior using a specific stiffener orientation. The simulation of a laser powder bed fusion process showed new opportunities for the application of this technology to stiffened panel manufacturing. [ABSTRACT FROM AUTHOR]

This editorial launches REGION, the new online and open-access journal of ERSA. REGION aims to be a high-quality academic journal in the field of regional science. To its contributors, it offers a solid peer-review process and immediate publication upon acceptance. Also, it will be a flexible outlet, not bound by traditional journal formats or strict page limits. To its readers, the journal offers high-standard publications on current issues in regional science that are easily accessible through its website. Both submitting to the journal and accessing the contributions are free of charge to everyone.

Nonlinear estimation of the gravity model with Poisson-type regression methods has become popular for modelling international trade flows, because it permits a better accounting for zero flows and extreme values in the distribution tail. Nevertheless, as trade flows are not independent from each other due to spatial and network autocorrelation, these methods may lead to biased parameter estimates. To overcome this problem, eigenvector spatial filtering (ESF) variants of the Poisson/negative binomial specifications have been proposed in the literature on gravity modelling of trade. However, no specific treatment has been developed for cases in which many zero flows are present. This paper contributes to the literature in two ways. First, by employing a stepwise selection criterion for spatial filters that is based on robust (sandwich) p-values and does not require likelihood-based indicators. In this respect, we develop an ad hoc backward stepwise function in R. Second, using this function, we select a reduced set of spatial filters that properly accounts for importer-side and exporter-side specific spatial effects, as well as network effects, both at the count and the logit processes of zero-inflated methods. Applying this estimation strategy to a cross-section of bilateral trade flows between a set of 64 countries for the year 2000, we find that our specification outperforms the benchmark models in terms of model fitting, both considering the AIC and in predicting zero (and small) flows.

This research presents a new beam finite element capable of predicting static and dynamic behavior of beam structures with bending-torsion coupling. The model here derived establishes a relation between the bending and torsional nodal degree of freedom of a two node beam element. The equilibrium equations are derived neglecting the non-linear terms while the stiffness and mass matrices are derived with Galerkin's method. The shape functions are obtained considering Timoshenko's hypothesis and the torsional moment constant along the element. The model has been validated through numerical and experimental results for static and dynamic simulation. The comparison revealed a relative difference mostly lower than 5% for static deformations and natural frequency prediction, while the Modal Assurance Criterion (MAC) confirmed the consistency with numerical and experimental results in terms of mode shape similarity. [ABSTRACT FROM AUTHOR]