University of Cagliari

This paper describes new approaches to the solution of a sequence of large linear systems of equations or large linear least squares problems with the same matrix and several right-hand side vectors that represent data. We consider both the situations when the matrix of the systems to be solved is fairly well-conditioned and when the matrix is very ill-conditioned. In the latter case regularization is applied. We are concerned with the situation when the matrix is too large to make the application of direct solution methods possible or attractive. Our solution methods apply flexible Arnoldi or flexible Golub-Kahan decompositions. These decompositions allow the solution subspace computed during the solution of a seed system to be expanded by residual vectors that are computed during the solution of subsequent systems. Computed examples illustrate the competitiveness of the proposed methods.

Guiding molecular assembly of peptides into rationally engineered nanostructures remains a major hurdle against the development of functional peptide‐based nanomaterials. Various non‐covalent interactions come into play to drive the formation and stabilization of these assemblies, of which electrostatic interactions are key. Here, the atomistic mechanisms by which electrostatic interactions contribute toward controlling self‐assembly and lateral association of ultrashort β‐sheet forming peptides are deciphered. Our results show that this is governed by charge distribution and ionic complementarity, both affecting the interaction patterns between charged residues: terminal, core, and/or terminal‐to‐core attraction/repulsion. Controlling electrostatic interactions enabled fine‐tuning nanofiber morphology for the 16 examined peptides, resulting into versatile nanostructures ranging from extended thin fibrils and thick bundles to twisted helical “braids” and short pseudocrystalline nanosheets. This in turn affected the physical appearance and viscoelasticity of the formed materials, varying from turbid colloidal dispersions and viscous solutions to soft and stiff self‐supportive hydrogels, as revealed from oscillatory rheology. Atomistic mechanisms of electrostatic interaction patterns were confirmed by molecular dynamic simulations, validating molecular and nanoscopic characterization of the developed materials. In essence, detailed mechanisms of electrostatic interactions emphasizing the impact of charge distribution and ionic complementarity on self‐assembly, nanostructure formation, and hydrogelation are reported.

Study Objectives This study aimed to investigate the effect of dopamine agonists (DA) and Clonazepam on Large Muscle Group Movements during sleep (LMM), a distinct motor phenomenon, in Restless Legs Syndrome (RLS). Methods A retrospective analysis was conducted on 51 drug-free adult patients with RLS, divided into three groups: 33 received a DA (pramipexole or ropinirole), 15 received clonazepam, and 18 received a placebo. Each patient underwent two consecutive nocturnal polysomnographic (PSG) recordings: one baseline and one following treatment administration. LMM and periodic leg movements during sleep (PLMS) were scored. Differences between groups were analyzed using ANCOVA, with the International Restless Legs Syndrome Study Group severity scale as a covariate, and within-group changes were assessed using paired t-tests. Results At baseline, no significant difference in LMM or PLMS was observed between groups. Following treatment, DA significantly reduced PLMS and periodicity indexes but did not significantly alter LMM indexes, except for a small increase in LMM duration. The placebo group exhibited a significant decrease in LMM index during the second night, potentially reflecting a first-night effect (FNE). Clonazepam did not significantly affect either PLMS or LMM. Conclusions DA effectively reduced PLMS but did not significantly impact LMM, suggesting that LMM may involve different neurophysiological mechanisms. The potential FNE observed in the placebo group underscores the need for careful consideration of adaptation effects in sleep studies. Future research should explore alternative or adjunctive therapies targeting LMM and residual sleep disturbances in RLS.

Much has been written to address the increasing complexity of youth temporalities, especially through a focus on when adulthood is reached, an approach that informs the tradition of youth studies called “youth transitions.” This article discusses some of the shortcomings of this approach that were revealed during the global pandemic, through the social distancing measures that were put in place in response to it and how young people reacted to new imposed rhythms. The pandemic has predominantly been seen as a “suspension,” with implications in particular on two different temporal dimensions: on the one hand, young people have experienced profound changes in their everyday lives due to lockdown restrictions; and, on the other hand, at the biographical level, a search for alternative lifestyles has emerged, impacting on mid-term perspectives. These changes urge us to reconsider various phenomena of time suspension associated with youth, such as moratorium and waithood, paying attention to the value that young people attribute them. Borrowing from Flaherty’s work on time work, this article discusses various nuances of time suspensions that allow us to examine agency transformations during the pandemic. It does so by looking at a case study of young people in Italy, and how a disregard for the temporalities that are typical of value to youth appears to have taken place, based on documentary sources and qualitative material analyzed for a project called IANG. By reflecting on the changes in the ways of looking at young people during the pandemic, and zooming in on some rituals that were reworked due to lockdown restrictions such as the final school exam, I conclude that we should shift attention from “timing transitions,” to “times” in transition, and look more attentively at the meanings attributed to various forms of time suspension that make up youth through specific youth temporalities.

This article aims to discuss the issue of political agency in the context of the climate crisis. In this regard, the article reports and analyzes the outlines of the debate on the relationship between human beings and the non-human world, and takes Bruno Latour’s theoretical proposal and some criticisms of it as a reference. For the most part, this debate revolves around ontological questions concerning the status of human beings in the world. Such questions provide arguments for better understanding whether politics represents an autonomous dimension in which human agency possesses a peculiar meaning or not.

Background Stiff Person Spectrum Disorders (SPSD) are classically defined by the presence of muscle stiffness, spasms and hyperactivity of the central nervous system. There is a notable correlation between neurophysiological features and the clinical hallmark of SPSD, which has greatly encouraged the use of these techniques for diagnostic purposes. Besides, electrophysiological techniques allow for a functional evaluation of the ‘hyperactivity of the CNS’, thus offering the opportunity to clarify the mechanisms underlying this disorder. This review delves into the current knowledge on the electrophysiological aspects of SPSD, highlighting the pivotal role of various studies in unravelling its pathophysiology. Methods Literature review for studies on SPSD that included a neurophysiological evaluation. Results We first examined the abnormal neurophysiological findings of SPSD across the central nervous system, from the spinal circuit to the motor cortex. Subsequently, we discussed their pathological implications and explored how these findings can be interpreted within the framework of an immune-mediated disorder. Conclusions Two primary questions remain unanswered: the localization of the primary abnormality within the central nervous system and the connection between the autoimmune basis of SPSD and its neurophysiological aspects. Addressing these questions could provide invaluable insights into SPSD etiology and targeted therapeutic strategies.

Purpose To evaluate the incidence and to describe the characteristics of the intrableb pigmentation (IBP) following XEN63 implantation. Methods Retrospective case series of three eyes presenting a pigment dispersion in the filtering bleb after a XEN63 implantation for uncontrolled IOP. Demographic, clinical and imaging data were obtained from medical records. Results Three out of 40 patients who underwent XEN implantation (average age 70.67 years) showed an IBP during the 12 months postoperative period. The mean time of IBP onset was 50 days (range, 15–90). The slit lamp examination showed two IBP patterns: a “diffuse” pattern (2 patients) with multiple spots of pigmentation inside the bleb; a “punctiform” pattern (1 patient), with a single spot at the distal end of the device. The AS-OCT imaging confirmed the presence of IBP appearing as a hyperreflective spot/s in the context of the filtering bleb. The patient with the punctiform IBP experienced a distal XEN ostium obstruction with a decrease in bleb function. In one case the diffuse IBP occurred after a successful needling procedure. All the patients’ IOP reported at the end of the follow-up was below 21 mmHg. Conclusion The development of IBP might occur after XEN implantation in various times and with different patterns. The IBP pattern can provide meaningful clues on the bleb filtering function. A proper follow-up based on slit lamp biomicroscopy, IOP measurement, and AS-OCT imaging is recommended to manage potential complications related to IBP.

Background Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents. Objectives We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics. Design This is a retrospective real-world cohort study of BRAF V600E mutated mCRC patients treated with second-line EC ± B at 20 Italian centres. Methods Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients. Results A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases (p = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR)DpR ⩾30%: 0.52, 95% CI: 0.30–0.90, p = 0.02) and median cut-off values (HRDpR⩾15%: 0.55, 95% CI: 0.33–0.92, p = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78–0.98, p = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR (pDpR⩾30% = 0.04; pDpR⩾15% = 0.04; pcont. = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected. Conclusion A DpR of at least 15% independently predicts PFS benefit in BRAF V600E mutated mCRC patients treated with second-line EC ± B.

Myeloid sarcoma (MS) is an extramedullary localization of immature granulocyte cells that can occur in association with acute myeloid leukemia (AML). Gastrointestinal involvement is relatively common in MS, but exclusive colonic localization is a rare occurrence. Here, we report on a 53-year-old male patient affected by AML developing a severe abdominal pain caused by intestinal perforation requiring surgical intervention. The post-mortem examination revealed an infiltrate consistent with MS. Diagnosis of colonic MS can be difficult due to non-specific symptoms and complicated by the challenges associated with exploring this area. Clinical acumen is crucial to promptly establish adequate management due to the potentially life-threatening nature of this condition.

In an increasingly complex world, the development of logical reasoning skills is vital for students of all ages. This study investigates the impact of the Logical Intelligence Enhancement Program (LIEP) on the logical reasoning skills of a large sample of primary school students aged between eight and eleven. The research encompasses 54 classes across nine Italian state primary schools, with half of the classes participating in the LIEP training and the other half forming the control group. Results demonstrate significant improvements in logical reasoning abilities among the students who participated in the LIEP training, as indicated by both near and far effects on tasks assessing logical reasoning (an LIEP-like task for near effect and the Matrix Reasoning subtest of the WISC-IV for far effect). Student and teacher feedback reinforces the programme’s positive influence on cognitive development and learning experiences. These findings underscore the potential value of LIEP for strengthening critical thinking skills in primary education.

The precious red coral Corallium rubrum (Linnaeus, 1758) is a charismatic species living in the Mediterranean Sea and its Atlanticsurroundings, known for its slow growth and long lifespan. The development of a reliable method for assessing colony age hasenabled the comparison of average annual growth rates, minimising age-related variability. This study aimed to investigate thepotential effect of depth on colony growth by analysing a set of morphometric parameters - basal diameter, height, weight, totalbranch length (TBL), and number of apexes - normalised per year. The analysis was conducted on 59 specimens collected fromshallow (<60 m) and mesophotic (>60 m) banks along the Italian coast, which are subject to diverse environmental conditions.The colonies’ estimated average age was approximately 30 years, regardless of depth. Notably, the annual growth rate in weightwas significantly higher in colonies from the deeper depth range, while growth rates for the other morphometric parametersshowed no variation with depth. (PDF) Are colony growth rates depth-dependent in the Mediterranean red coral?. Available from: https://www.researchgate.net/publication/387784360_Are_colony_growth_rates_depth-dependent_in_the_Mediterranean_red_coral [accessed Jan 10 2025].

Pain is one of the most frequently reported symptoms in hemodialyzed (HD) patients, with prevalence rates between 33% and 82%. Risk factors for chronic pain in HD patients are older age, long-lasting dialysis history, several concomitant diseases, malnutrition, and others. However, chronic pain assessment in HD patients is rarely performed by specialists in pain medicine, with relevant consequences in terms of diagnostic and treatment accuracy. Furthermore, no study has used the recently introduced International Association for the Study of Pain (IASP) pathophysiological classification. In this observational, cross-sectional study in a tertiary HD center in Northern Italy, we analyzed data regarding HD patients, evaluated for 5 months in 2021 by specialists in pain medicine and aimed to identify and characterize chronic pain according to the IASP definition and the last 2019 classification of chronic pain for ICD-11. Pain severity was evaluated by the pain severity score of the brief pain inventory tool. Among 213 patients, 65 (31%) suffered from chronic pain. The average age was 73.1 years; 55.5% of the patients were male; 53.7% had diabetes, and 39.2% had arterial hypertension. Of the 54 patients subjected to an in-depth evaluation, data regarding 113 pain diagnoses were extracted, particularly related to osteoarthritis, obliterating arterial disease, and low back pain with or without radiculopathy. On the basis of these diagnoses, the pain classification according to the IASP pathophysiological definition highlighted a predominant nociceptive pain type (53.9% of all the diagnoses), followed by neuropathic (22.1%), mixed (22.1%), nociplastic (2.6%), and idiopathic (2.6%) pain. According to the IASP classification for ICD-11, the clinical diagnosis of chronic pain secondary to obliterating arterial disease and diabetes-related foot ulcers could not be assigned to any diagnostic category as a result of the lack of a specific item in the aforementioned classification. This study confirmed that chronic pain is a common, burdening issue in hemodialysis patients and that it is of a prevalent nociceptive nature. Our study highlights some limitations of the last IASP ICD-11 classification, especially the lack of specific items for some pain features that are very frequent in hemodialysis patients, and not only in that population. Finally, this study underlines the importance of mutual collaboration between pain physicians and nephrologists for the well-being of patients of high clinical complexity, such as those undergoing chronic hemodialysis.

Background Cognitive reserve (CR) represents the susceptibility to age‐related brain changes or Alzheimer’s disease‐related pathology. It is the ability to withstand the effects of aging and neurological damage. Several factors influence CR, including education, work, activites, mental activity, and social networks, which play a crucial role in an individual’s ability to preserve the global cognitive functioning and counteract cognitive decline. Boosting cognitive reserve has become a relevant focus in our efforts. In this study, we aim to investigate how cognitive reserve could influence the cognitive decline in the elderly. Method Targeted neuropsychological assessment were administered to patients with Mild cognitive Impairment and dementia. We analyse through software R 4.3.2., the relationship between of cognitive reserve and other cognitive functions such as attention and memory capabilities. Results Our preliminary findings suggest a clear correlation between higher cognitive reserve and improved performance on these tests. This connection appeared particularly significant in the early stages of deterioration (Mild Cognitive Impairment). In other words the notion of cognitive reserve posits the prospect of interventions capable of mitigating cognitive aging or diminishing the susceptibility to dementia. Conclusions CR has a key role across the aging. In particular individuals with MCI could prevent and contrast cognitive decline boosting their CR, for example doing more activities, learning new language, gaining new skills, doing physical activities. Further research is needed to fully grasp this relationship and devise methods to extend cognitive reserve in order to promote cognitive health.

Ovarian lesions are common and often incidentally detected. A critical shortage of expert ultrasound examiners has raised concerns of unnecessary interventions and delayed cancer diagnoses. Deep learning has shown promising results in the detection of ovarian cancer in ultrasound images; however, external validation is lacking. In this international multicenter retrospective study, we developed and validated transformer-based neural network models using a comprehensive dataset of 17,119 ultrasound images from 3,652 patients across 20 centers in eight countries. Using a leave-one-center-out cross-validation scheme, for each center in turn, we trained a model using data from the remaining centers. The models demonstrated robust performance across centers, ultrasound systems, histological diagnoses and patient age groups, significantly outperforming both expert and non-expert examiners on all evaluated metrics, namely F1 score, sensitivity, specificity, accuracy, Cohen’s kappa, Matthew’s correlation coefficient, diagnostic odds ratio and Youden’s J statistic. Furthermore, in a retrospective triage simulation, artificial intelligence (AI)-driven diagnostic support reduced referrals to experts by 63% while significantly surpassing the diagnostic performance of the current practice. These results show that transformer-based models exhibit strong generalization and above human expert-level diagnostic accuracy, with the potential to alleviate the shortage of expert ultrasound examiners and improve patient outcomes.

The study has investigated the implications of three estimation methods, namely L-moments, Maximum Likelihood, and Maximum Product of Spacing (MPS), for fitting the four-parameter Kappa Distribution (KAPD) in extreme value analysis using Monte Carlo simulations. The accuracy of the estimates has been evaluated using root mean square error (RMSE) and bias. The paper also includes an analysis of the effect of the estimation method on the estimated quantiles considering a real-life example of annual maximum peak flows and the Generalized Normal Distribution as the error distribution. Assessment metrics of the empirical analysis include standard error, L-scale, and 90% confidence limits of the estimated quantiles. The results reveal that MPS is a preferred method of estimation of parameters for KAPD, i.e. having the lowest RMSE values, especially in the presence of heavier tail and significant positive skewness for small to very large sample sizes. Secondly, the method of L-moments is recommended due to its low bias while analyzing the distribution of shape parameters having a slightly heavier tail, and slight or moderate positive skewness. The results associated with the quality of estimated quantiles using real-life data are consistent with the findings of simulation outcomes.

The use of cold plasma is effective in overcoming seed dormancy. However, its effects, both in the long-term and during storage, is still not fully understood. The aim of this study, therefore, was to evaluate the immediate and post-storage effect of atmospheric plasma on the seeds of Pityrocarpa moniliformis in overcoming seed coat dormancy. The seeds were treated with plasma for 0, 1.0, 2.0, 3.0, 4.0 and 5.0 minutes. Following application, 50% of the seeds were stored for two years while the remainder were submitted to immediate analysis. The seeds were evaluated for germination and the germination speed index, in addition to seedling length and dry weight. The experimental design was completely randomised, and included regression analysis. The plasma treatment resulted in an increase in the germination rate and vigour of the seeds, both immediately after exposure and after two years of storage. In particular, the seeds treated for five minutes showed around 39% germination, which was outstanding compared to seeds from other exposure times. Plasma is effective in overcoming seed coat dormancy in seeds of P. moniliformis treated for five minutes and tested immediately. The effect of plasma on the seeds of P. moniliformis after storage was less for all the conditions under test. Key words: Atmospheric plasma; Germination potential; Forest species; Post-storage viability; Tegumentary dormancy.

Dry eye disease (DED) is a multifactorial, chronic, and often relapsing condition with a significant impact on patient quality of life (QoL). Symptoms such as ocular discomfort and visual disturbances are diverse and frequently misaligned with objective clinical signs, complicating diagnosis and management. DED not only interferes with daily activities like reading, driving, and computer use but also imposes a substantial economic burden due to direct healthcare costs and reduced work productivity. Beyond its ocular manifestations, DED has been associated with higher prevalence rates of depression and anxiety, with a complex bidirectional relationship. Patients with DED may experience psychological distress that exacerbates symptoms, leading to a vicious cycle that further impairs QoL. This underscores the importance of integrating mental health screening into the management of DED, particularly for high-risk populations. Optimizing the care of DED patients requires empathy, effective communication, and the establishment of a therapeutic alliance that acknowledges patient experiences and involves them in personalized treatment plans. Such an approach can improve patient satisfaction, enhance treatment adherence, and address both ocular and psychological dimensions of the disease. This paper highlights current evidence on the impact of DED symptoms and its association with mental health and recommends strategies to improve clinical management through a patient-centered approach.