Università degli Studi di Brescia
Recent publications
Nonlinear frequency generation at the nanoscale is a hot research topic which is gaining increasing attention in nanophotonics. The generation of harmonics in subwavelength volumes is historically associated with the enhancement of electric fields in the interface of plasmonic structures. Recently, new platforms based on high-index dielectric nanoparticles have emerged as promising alternatives to plasmonic structures for many applications. By exploiting optically induced electric and magnetic response via multipolar Mie resonances, dielectric nanoelements may lead to innovative opportunities in nanoscale nonlinear optics. Dielectric optical nanoantennas enlarge the volume of light–matter interaction with respect to their plasmonic counterpart, since the electromagnetic field can penetrate such materials, and therefore producing a high throughput of the generated harmonics. In this review, we first recap recent developments obtained in high refractive index structures, which mainly concern nonlinear second order effects. Moreover, we discuss configurations of dielectric nano-devices where reconfigurable nonlinear behavior is achieved. The main focus of this work concerns efficient Sum Frequency Generation in dielectric nano-platforms. The reported results may serve as a reference for the development of new nonlinear devices for nanophotonic applications.
Background Early start of highly active antiretroviral therapy (HAART) in perinatally HIV-1 infected children is the optimal strategy to prevent immunological and clinical deterioration. To date, according to EMA, only 35% of antiretroviral drugs are licenced in children < 2 years of age and 60% in those aged 2–12 years, due to the lack of adequate paediatric clinical studies on pharmacokinetics, pharmacodynamics and drug safety in children. Methods An observational retrospective study investigating the rate and the outcomes of off-label prescription of HAART was conducted on 225 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results 22.2% (50/225) of included children were receiving an off-label HAART regimen at last check. Only 26% (13/50) of off-label children had an undetectable viral load (VL) before the commencing of the regimen and the 52.0% (26/50) had a CD4 + T lymphocyte percentage > 25%. At last check, during the off label regimen, the 80% (40/50) of patients had an undetectable VL, and 90% (45/50) of them displayed CD4 + T lymphocyte percentage > 25%. The most widely used off-label drugs were: dolutegravir/abacavir/lamivudine (16%; 8/50), emtricitbine/tenofovir disoproxil (22%; 11/50), lopinavir/ritonavir (20%; 10/50) and elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (10%; 10/50). At logistic regression analysis, detectable VL before starting the current HAART regimen was a risk factor for receiving an off-label therapy (OR: 2.41; 95% CI 1.13–5.19; p = 0.024). Moreover, children < 2 years of age were at increased risk for receiving off-label HAART with respect to older children (OR: 3.24; 95% CI 1063–7.3; p = 0.001). Even if our safety data regarding off-label regimens where poor, no adverse event was reported. Conclusion The prescription of an off-label HAART regimen in perinatally HIV-1 infected children was common, in particular in children with detectable VL despite previous HAART and in younger children, especially those receiving their first regimen. Our data suggest similar proportions of virological and immunological successes at last check among children receiving off-label or on-label HAART. Larger studies are needed to better clarify efficacy and safety of off-label HAART regimens in children, in order to allow the enlargement of on-label prescription in children.
Background Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design. Methods A standardized neuropsychological test battery covering six cognitive domains was completed by 69 C9orf72 , 41 GRN , and 28 MAPT mutation carriers with CDR® plus NACC-FTLD ≥ 0.5 and 275 controls. Logistic regression was used to identify the combination of tests that distinguished best between each mutation carrier group and controls. The composite scores were calculated from the weighted averages of test scores in the models based on the regression coefficients. Sample size estimates were calculated for individual cognitive tests and composites in a theoretical trial aimed at preventing progression from a prodromal stage (CDR® plus NACC-FTLD 0.5) to a fully symptomatic stage (CDR® plus NACC-FTLD ≥ 1). Time-to-event analysis was performed to determine how quickly mutation carriers progressed from CDR® plus NACC-FTLD = 0.5 to ≥ 1 (and therefore how long a trial would need to be). Results The results from the logistic regression analyses resulted in different composite scores for each mutation carrier group (i.e. C9orf72 , GRN , and MAPT ). The estimated sample size to detect a treatment effect was lower for composite scores than for most individual tests. A Kaplan-Meier curve showed that after 3 years, ~ 50% of individuals had converted from CDR® plus NACC-FTLD 0.5 to ≥ 1, which means that the estimated effect size needs to be halved in sample size calculations as only half of the mutation carriers would be expected to progress from CDR® plus NACC FTLD 0.5 to ≥ 1 without treatment over that time period. Discussion We created gene-specific cognitive composite scores for C9orf72 , GRN , and MAPT mutation carriers, which resulted in substantially lower estimated sample sizes to detect a treatment effect than the individual cognitive tests. The GENFI-Cog composites have potential as cognitive endpoints for upcoming clinical trials. The results from this study provide recommendations for estimating sample size and trial duration.
Background Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICP tcd ) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICP tcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICP i ), in excluding the presence of intracranial hypertension. Methods This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICP tcd ) with a reference standard (ICP i ), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICP i monitoring, were enrolled in 16 international intensive care units. ICP i measurements (reference test) were compared to simultaneous ICP tcd measurements ( index test) at three different timepoints: before, immediately after and 2 to 3 h following ICP i catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICP i thresholds (> 20, > 22 and > 25 mmHg) to assess ICP tcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICP tcd. Results Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICP tcd and ICP i was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICP tcd in excluding intracranial hypertension. Concordance correlation between ICP tcd and ICP i was 33.3% (95% CI 25.6–40.5%), and Bland–Altman showed a mean bias of -3.3 mmHg. The optimal ICP tcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7–92.6%) and a specificity of 72% (95% CI 51.9–94.0%) with an AUC of 76% (95% CI 65.6–85.5%). Conclusions and relevance ICP tcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. Trial registration : NCT02322970 .
The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer’s or Parkinson’s disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.
Survival has been considered the cornerstone for clinical outcome evaluation in critically ill patients admitted to intensive care unit (ICU). There is evidence that ICU survivors commonly show impairments in long-term outcomes such as quality of life (QoL) considering them as the most relevant ones. In the last years, the concept of patient-important outcomes has been introduced and increasingly reported in peer-reviewed publications. In the present systematic review, we evaluated how many randomized controlled trials (RCTs) were conducted on critically ill patients and reporting a benefit on survival reported also data on QoL. All RCTs investigating nonsurgical interventions that significantly reduced mortality in critically ill patients were searched on MEDLINE/PubMed, Scopus and Embase from inception until August 2021. In a second stage, for all the included studies, the outcome QoL was investigated. The primary outcome was to evaluate how many RCTs analyzing interventions reducing mortality reported also data on QoL. The secondary endpoint was to investigate if QoL resulted improved, worsened or not modified. Data on QoL were reported as evaluated outcome in 7 of the 239 studies (2.9%). The tools to evaluate QoL and QoL time points were heterogeneous. Four interventions showed a significant impact on QoL: Two interventions improved survival and QoL (pravastatin in subarachnoid hemorrhage, dexmedetomidine in elderly patients after noncardiac surgery), while two interventions reduced mortality but negatively influenced QoL (caloric restriction in patients with refeeding syndrome and systematic ICU admission in elderly patients). In conclusion, only a minority of RCTs in which an intervention demonstrated to affect mortality in critically ill patients reported also data on QoL. Future research in critical care should include patient-important outcomes like QoL besides mortality. Data on this topic should be collected in conformity with PROs statement and core outcome sets to guarantee quality and comparability of results.
Background Cor triatriatum is a rare congenital heart disease representing the 0.4% of all congenital cardiac anomalies. To date, no specific genetic alteration has been associated to cor triatriatum. The left-sided presentation (cor triatriatum sinister (CTS)) generally consists in a fibromuscular membrane that divides the left atrium into two chambers, therefore generating a varying grade of flow obstruction depending on the shape, location, and membrane fenestration size. Cor triatriatum sinister can be isolated or associated to other congenital heart defects such as ostium secundum atrial septal defect, patent foramen ovale or abnormal pulmonary veins drainage. Case presentation Our case is a 63-year-old woman who was diagnosed with a non-restrictive membrane during a hospitalization for acute heart failure. In the following 6 months, she started to become symptomatic. However, the onset of symptoms was more likely related to mitral valve regurgitation worsening and previously unknown coronary artery disease, rather than to CTS. She underwent bi-atrial surgical ablation (Cox Maze IV procedure) for atrial fibrillation (AF), surgical resection of interatrial membrane with mitral annuloplasty, and myocardial revascularization. Conclusion The onset and severity of symptoms in patients with CTS mostly depend on membrane fenestration size, grade of stenosis generated and pulmonary veins drainage site. However, some cases may remain asymptomatic until adulthood; the degree of pulmonary hypertension and congestive heart failure is determined by the presence of additional cardiac anomalies and the fibromuscular membrane fenestration. In some cases, CTS may remain asymptomatic, thus the diagnosis can be incidental.
Adolescence is characterized by emotional instability and risk-taking behaviours that can lead to, among other things, an increased risk of developing pathological video-gaming and gambling habits. The aim of this Study is to assess the prevalence and type of video gaming and gambling habits in adolescent students attending Italian upper-secondary schools. The cross-sectional study was conducted via an online survey using validated questionnaires. The primary outcome measures were the prevalence of past-year video gaming and gambling activities. The sample consisted of 502 adolescent students from first- and second-grade secondary schools. A total of 40.8% of participants were video gamers, 4.8% were gamblers, 17.8% were both video gamers and gamblers, and the remaining 36.6% were not players. Among participants who reported video gaming activity ( n = 294), 68.0% were classified as nonproblem gamers, 24.5% as at-risk gamers, and 7.5% as disordered video gamers. Among the participants who reported gambling activity ( n = 113), 85.8% were not problematic gamblers, 8.9% were at-risk gamblers, and 5.3% were pathological gamblers. Only 0.2% of all subjects met the criteria for both pathological gambling and pathological video game use. The findings indicate that video gaming and gambling are common leisure times among adolescent students. However, a small but significant minority of these adolescents met the criteria for either severe problem gaming or gambling or both.
A code C⊆{0,1,2}n is said to be trifferent with length n when for any three distinct elements of C there exists a coordinate in which they all differ. Defining T(n) as the maximum cardinality of trifferent codes with length n, T(n) is unknown for n≥5. In this note, we use an optimized search algorithm to show that T(5)=10 and T(6)=13.
The growing demand for electric energy and the development of green sources such as photovoltaic and wind power are requiring the integration of new systems in the already developed transmission network. This task is not always straightforward, since when a large amount of power is not used, it gives rise to reactive loads. Usually, to put back into phase the voltage and the current, specific devices such as reactors are applied at the electric station level. One of the practices that are becoming increasingly common is the use of two autotransformers adopting the tap-staggering technique. In this way, already existing devices can be used to rearrange the electric line parameters. One of the downsides is that, related to the specific design of the transformers, high magnetic flux can occur in the core. Due to overexcitation, vibrations generated by magnetostriction can become extremely high and can bring to damages that in some cases can cause an impairment of the device. This article aims to find suitable parameters able to predict the approaching of a limit condition beyond which the autotransformer can undergo damage. For this purpose, experimental investigations considering the vibrations and the noise emitted by five autotransformers were carried out in different tap staggering conditions. It was found that the acceleration values very much depend on the position of the transducer, while the acoustic noise measurements give an average of the sound radiated by the different parts of the autotransformers but depend on the distance from the case of the device. For this reason, it is advised not to exceed an average overall value of 80 dB(A) sound pressure level at a 2 m distance from the autotransformer.
The addition of storage capacity to district heating systems increases flexibility and expands the range of usable heat sources. Despite their apparently simple nature, thermal energy storage (TES) tanks display a wide range of performances due to different construction and operation choices, as proven by numerous literature studies. However, most of the investigations focus on domestic-size tanks of few cubic metres or, on the other hand, very large seasonal storages of hundreds of thousands of cubic metres. In this work, the performances of a 5000 m³ TES recently introduced in a district heating network in Brescia, Italy, are experimentally analysed using temperature and flow rate measurements acquired over two months in the heating season. First-law efficiencies, exergy, and stratification parameters are calculated and discussed. Energy and exergy efficiencies computed for all examined cycles are above 90%, in line with literature values for smaller and larger TESs. The thermocline profile is generally stable through the cycle unless anomalous events occur, and its average thickness is below 4% of the water height. The combined analysis of single-point indicators, thermocline profiles, and qualitative temperature heatmaps shows that short partial charge/discharge events followed by long stand-by periods negatively affect performances. Stratification efficiency and stratification number give further time-dependent information on the vertical distribution of temperatures in the TES. Heat losses towards the outside are also estimated and discussed in the light of integrative measurements performed on other TESs with similar characteristics, showing that particular care must be paid to the top, where dissipation could be increased by evaporation phenomena if the water surface is not protected.
The aim of this work was to assess the impact of a novel P nanofertilizer (P-NF) on P solubility, microbial toxicity, soil respiration rate, soil enzyme activity and soil microbial community composition of two soils with contrasting properties in a laboratory incubation study. From the comparison with a commercial triple superphosphate (TSP), the P-NF induced lower release of soluble P, did not cause microbial toxicity, nor reduced soil respiration. Among the measured enzyme activities involved in C, N, P and S mineralization, only the protease activity was significantly inhibited by the P-NF in both the studied soils. Analysis of soil microbial communities showed no significant impacts on bacteria, fungi and archaea, after 1 and 7 d of incubation. We concluded that the tested novel P-NF could be safely used in agriculture.
Cutaneous sarcomas are a heterogeneous group of rare mesenchymal neoplasms representing less than 1% of malignant tumors. Histology report remains the cornerstone for the diagnosis of these tumors. The most important clinicopathologic parameters related to prognosis include larger tumor size, high mitotic index, head and neck location, p53 mutations, depth of infiltration and histological grade, vascular and perineural invasion as well as the surgical margins status. Applying advanced biopsy techniques might offer more precise assessment of surgical margins, which constitutes a significant precondition for the management of these tumors. The management of cutaneous soft tissue sarcomas requires a multidisciplinary approach. Surgery remains the standard treatment, nonetheless adjuvant therapy may be required, consisting of radiotherapy, chemotherapy, and molecular targeted therapies to improve treatment outcomes. The role of molecular profiling in the treatment of uncontrolled disease is promising, but it may be offered to a relatively small proportion of patients and its use is still considered experimental in this setting. Due to the rarity of the disease, there is a need for knowledge and experience to be shared, pooled, organized and rationalized so that recent developments in medical science can have a major impact on the disease course. Multicenter clinical trials are needed to improve the care of patients with cutaneous sarcomas.
This study aimed to examine the association between socioeconomic status (SES) and self-rated health (SRH) among US adults and the extent to which blood and urinary metal mixtures explain this association. We used 14 years of repeated cross-sectional data that consists of seven consecutive NHANES cycles from 2003 to 2016 (n = 9497). SRH was measured using a 5-point Likert scale, and SES was measured by family income to poverty ratio (FMPIR), levels of education, and employment status. Blood concentration of lead, mercury, and cadmium, and urinary concentrations of ten heavy metals (arsenic, barium, cadmium, cesium, cobalt, lead, mercury, molybdenum, thallium, tungsten) were used as metal mixtures. The total effect of SES on SRH was examined by linear regression model. The direct effect of SES on blood and urinary metal mixtures was examined by the weighted quantile sum (WQS) regression with repeated holdout validation method, and the average causal mediation effects of blood and urinary metal mixtures were examined by model-based causal mediation technique. Results showed that SES indicators [education β: 0.17; 95% Confidence Interval (CI): 0.15, 0.18; employment β: 0.16; 95% CI: 0.12, 0.21; and FMPIR β: 0.09; 95% CI: 0.08, 0.11] were significantly positively, and the WQS indices of blood and urine metal mixtures (blood β: −0.04; 95% CI: − 0.05, − 0.03, urine β: − 0.07; 95% CI: − 0.13, − 0.004) were significantly inversely associated with SRH in the US adults. The novel finding was the mechanism between SES and SRH that exposure to heavy metals may explain socioeconomic inequalities in SRH in the US general population. Longitudinal studies are needed to corroborate this study results.
People living with chronic disease (PLWCD) are the frailest category, both for the risk of severe COVID-19 illness and for the impact on the care continuum. Aim of this study was to analyze coping strategies and resilience in people living with HIV (PLWH) compared to people living with oncological diseases (PLWOD) during COVID-19 pandemic. We administrated an anonymous questionnaire, which explored the emotional experience, the demographic factors linked to a COVID-19-related stress syndrome, the patient’s perception about the adequacy of clinical undertaking from the hospital and the resilience. We analyzed 324 questionnaires. There were no significant differences in prevalence of psychological distress among the whole cohort; however, PLWOD were calmer, less troubled, and more serene than PLWH. Moreover, PLWH smoked more, ate more, and gained more weight than PLWOD. Most patients didn’t feel lonely and continued to take pleasure from their activities. No differences in resilience were found between the groups. In the whole cohort lower levels of resilience were found in patients that were unemployed, with history of psychological disorders and in those who experienced more feelings of anger, anxiety and concern. In our study, patients seemed to preserve their well-being, and to activate adaptive coping during the pandemic.
Cognitive impairment in schizophrenia represents one of the main obstacles to clinical and functional recovery. This expert group paper brings together experts in schizophrenia treatment to discuss scientific progress in the domain of cognitive impairment to address cognitive impairments and their consequences in the most effective way. We report on the onset and course of cognitive deficits, linking them to the alterations in brain function and structure in schizophrenia and discussing their role in predicting the transition to psychosis in people at risk. We then address the assessment tools with reference to functioning and social cognition, examining the role of subjective measures and addressing new methods for measuring functional outcomes including technology based approaches. Finally, we briefly review treatment options for cognitive deficits, focusing on cognitive remediation programs, highlighting their effects on brain activity and conclude with the potential benefit of individualized integrated interventions combing cognitive remediation with other approaches.
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3,648 members
Giovanna Mazzoleni
  • Department of Clinical and Experimental Sciences
Rita Rezzani
  • Department of Clinical and Experimental Sciences
Isabella Zanella
  • Department of Molecular and Translational Medicine
Filippo Marciano
  • Department of Mechanical and Industrial Engineering
via san Faustino 74b, 25122, Brescia, Italy
Head of institution
Prof. Maurizio Tira
+39-030 3717315