Development of a High-Efficiency Device for Thermal Neutron Detection Using a Sandwich of Two High-Purity 10B Enriched Layers.

The shortage of 3He, a crucial element widely used as a neutron converter in neutron detection applications, has sparked significant research efforts aimed at finding alternative materials, developing appropriate deposition methods, and exploring new detector architectures. This issue has required the exploration of novel approaches to address the challenges faced in neutron detection. Among the available conversion materials, 10B has emerged as one of the most promising choices due to its high neutron-capture cross-section and relatively high Q value. In our previous papers, we delved into the possibility of depositing neutron conversion layers based on 10B using Pulsed Laser Deposition (PLD). We investigated and evaluated the performance of these layers based on various factors, including deposition conditions, substrate properties, and film thickness. Moreover, we successfully developed and tested a device that employed a single conversion layer coupled with a silicon particle detector. In this current study, we present the development of a new device that showcases improved performance in terms of efficiency, sensitivity, and discrimination against γ background signals. The background signals can arise from the environment or be associated with the neutron field. To achieve these advancements, we considered a new detection geometry that incorporates the simultaneous use of two 10B conversion layers, each with a thickness of 1.5 µm, along with two solid-state silicon detectors. The primary objective of this design was to enhance the overall detection efficiency when compared to the single-layer geometry. By employing this novel setup, our results demonstrate a significant enhancement in the device's performance when exposed to a neutron flux from an Am-Be neutron source, emitting a flux of approximately 2.2 × 106 neutrons per second. Furthermore, we established a noteworthy agreement between the experimental data obtained and the simulation results.

Hydrogenated amorphous silicon high flux x-ray detectors for synchrotron microbeam radiation therapy.

Objective. Microbeam radiation therapy (MRT) is an alternative emerging radiotherapy treatment modality which has demonstrated effective radioresistant tumour control while sparing surrounding healthy tissue in preclinical trials. This apparent selectivity is achieved through MRT combining ultra-high dose rates with micron-scale spatial fractionation of the delivered x-ray treatment field. Quality assurance dosimetry for MRT must therefore overcome a significant challenge, as detectors require both a high dynamic range and a high spatial resolution to perform accurately.Approach. In this work, a series of radiation hard a-Si:H diodes, with different thicknesses and carrier selective contact configurations, have been characterised for x-ray dosimetry and real-time beam monitoring applications in extremely high flux beamlines utilised for MRT at the Australian Synchrotron.Results. These devices displayed superior radiation hardness under constant high dose-rate irradiations on the order of 6000 Gy s-1, with a variation in response of 10% over a delivered dose range of approximately 600 kGy. Dose linearity of each detector to x-rays with a peak energy of 117 keV is reported, with sensitivities ranging from (2.74 ± 0.02) nC/Gy to (4.96 ± 0.02) nC/Gy. For detectors with 0.8µm thick active a-Si:H layer, their operation in an edge-on orientation allows for the reconstruction of micron-size beam profiles (microbeams). The microbeams, with a nominal full-width-half-max of 50µm and a peak-to-peak separation of 400µm, were reconstructed with extreme accuracy. The full-width-half-max was observed as 55 ± 1µm. Evaluation of the peak-to-valley dose ratio and dose-rate dependence of the devices, as well as an x-ray induced charge (XBIC) map of a single pixel is also reported.Significance. These devices based on novel a-Si:H technology possess a unique combination of accurate dosimetric performance and radiation resistance, making them an ideal candidate for x-ray dosimetry in high dose-rate environments such as FLASH and MRT.

Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy.

BACKGROUND: Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. METHODS: Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. RESULTS: A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. CONCLUSIONS: In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

Short- and Long-Term Effects of a Multi-Component, Artificial Tear on Preocular Tear Film Stability, Tear Evaporation and Tear Film Optical Dynamic: A Prospective Randomized Double-Phase Study.

PURPOSE: To evaluate the short- (within 90 min) and long-term (after 21 days of treatment) effects of an artificial tear containing carbomer, hyaluronic acid, glycerol, and medium-chain triglycerides in patients with mild-to-moderate dry eye symptoms. METHODS: Subjects received the tested artificial tears in the right eye and control artificial tears in the left eye and were assessed 10, 30, 60, and 90 min after instillation in the short-term study phase. They received the study product in both eyes in the long-term phase. Non-invasive break-up time (NIBUT), tear lipid layer pattern, tear evaporation, and tear film objective optical dynamics (TFOOD) were measured in controlled environmental conditions. RESULTS: In total, 32 patients (10 males, mean age 42 ± 11 years) were enrolled. During the short-term phase, NIBUT increased significantly in the right eyes at all time points compared with baseline (all p < 0.05). Conversely, in the left eyes, NIBUT increased significantly at 10 and 30 min (p < 0.05). The tear evaporation values increased at 10 min and decreased at 30 and 60 min (p < 0.05) in the right eyes, while they increased only at 10 min (p < 0.05) in the left eyes. Compared with baseline, the TFOOD was significantly more stable at all time points in the right eyes (p < 0.05), while it was more stable at 10 and 30 min in the left eyes (p < 0.05). In the long-term phase, treated eyes showed a significant increase in NIBUT values, a significant reduction of tear evaporation, a significant improvement of tear lipid layer pattern, and a more stable TFOOD compared with baseline (all p < 0.05). Symptoms, measured with the Ocular Surface Disease Index questionnaire, were also significantly reduced compared with baseline (p < 0.05). CONCLUSION: The tested product increased tear film stability and reduced tear evaporation, normalizing lipid layer pattern and reducing symptoms in the short- and long-term observation.

Off-label use of combined antiretroviral therapy, analysis of data collected by the Italian Register for HIV-1 infection in paediatrics in a large cohort of children.

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.

A case of unilateral acute hypertensive uveitis in a child.

A 6-year-old boy was referred to our hospital for sudden blurring vision in the left eye. An ophthalmological evaluation showed white endothelial keratic precipitates and increased intra-ocular pressure. To our knowledge, this is the first reported case of hypertensive uveitis in children under 10 years of age and we also discuss the role of Epstein-Barr virus as a possible infectious trigger.

The use of antiviral drugs in children.

Viral infections are particularly common among children. They often have a mild course, are self-limiting and do not need any specific treatment. However, in some cases, the disease can be severe and lead to permanent disabilities. A variety of antiviral drugs are available for the treatments of certain infectious agents: for instance, acyclovir is used to treat herpes simplex virus encephalitis. Recommendations for flu treatment may change according to the current epidemiological surveillance data, on the basis of which antiviral sensibility can be forecast: recommended drugs for the 2020-21 flu season are oseltamivir, zanamivir, peramivir and baloxavir. Some drugs are used to treat congenital infections, such as valganciclovir and ganciclovir in congenital cytomegalovirus infection. Antiretroviral prophylaxis in newborns from HIV-1 infected mothers must be initiated as soon as possible, with one or more drugs according to therapeutic regimens based on the baby's risk category. According to the most recent guidelines, antiretroviral therapy must be started at diagnosis. Several antiretroviral drugs are available today and approved for use in children, so several combinations can be made. However, out of the 29 antiretroviral drugs approved for adults, only 38% (11/29) are approved for children under the age of two and about 60% (18/29) for children under the age of twelve. Treatment with direct antiviral agents against hepatitis C virus is approved for children over the age of three; it consists in different therapeutic regimens chosen on the basis of the viral genotype (ledipasvir/sofosbuvir for genotypes 1, 4, 5 and 6, sofosbuvir/ribavirin for genotypes 2 and 3, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for all genotypes) and it has dramatically changed the course of the illness. Many molecules have been studied in order to treat SARS-CoV-2 infection, but only remdesivir seems to play a role in shortening recovery time, although inclusion criteria are very specific and data on the use in children is limited.

Pulsed Laser Deposition of CsPbBr3 Films: Impact of the Composition of the Target and Mass Distribution in the Plasma Plume.

All-inorganic cesium lead bromine (CsPbBr3) perovskites have gained a tremendous potential in optoelectronics due to interesting photophysical properties and much better stability than the hybrid counterparts. Although pulsed laser deposition (PLD) is a promising alternative to solvent-based and/or thermal deposition approaches due to its versatility in depositing multi-elemental materials, deep understanding of the implications of both target composition and PLD mechanisms on the properties of CsPbBr3 films is still missing. In this paper, we deal with thermally assisted preparation of mechano-chemically synthesized CsPbBr3 ablation targets to grow CsPbBr3 films by PLD at the fluence 2 J/cm2. We study both Cs rich- and stoichiometric PbBr2-CsBr mixture-based ablation targets and point out compositional deviations of the associated films resulting from the mass distribution of the PLD-generated plasma plume. Contrary to the conventional meaning that PLD guarantees congruent elemental transfer from the target to the substrate, our study demonstrates cation off-stoichiometry of PLD-grown CsPbBr3 films depending on composition and thermal treatment of the ablation target. The implications of the observed enrichment in the heavier element (Pb) and deficiency in the lighter element (Br) of the PLD-grown films are discussed in terms of optical response and with the perspective of providing operative guidelines and future PLD-deposition strategies of inorganic perovskites.

Tuberculosis burden in immigrants and natives, adults and children, in Tuscany between 2000-2018.

BACKGROUND: Updated data on epidemiology of tuberculosis are needed in Italy. The aim of this study is to evaluate trends in incidence and associated lethality of tuberculosis in immigrants compared with Italians. METHODS: All tuberculosis cases diagnosed from 2000 to 2018 in 31 Tuscan hospitals were retrospectively identified. RESULTS: In 10,827 tuberculosis cases 6715 were males (62%), 4312 (60%) were Italian-born. Hospitalization rate was 15.37/100,000 population/year. The most common comorbidity were liver disease (832/10,827; 7.7%), COPD (675/10,827; 6.2%), cancer (614/10,827; 5.7%). HIV was more frequent in the immigrants (p < 0.001). Extra-pulmonary tuberculosis cases (EPTB) were mainly localized in pleura (740/3,894, 19%) and lymph nodes (449/3,894, 11,5%). HIV was associated with an increased risk of EPTB (OR 3.51 95% CI 2.92-4.23, p < 0.0001). EPTB risk was increased in South Asian-born patients (OR 1.77, 95% CI 1.46-2.15, p < 0.0001) as well in African-born patients (OR 1.13, 95% CI 1.03-1.24, p = 0.0091), who were at risk for gastroenteric tuberculosis (OR 3.74, 95% CI 2.69-5.22, p < 0.0001). Overall mortality rate was 0.006 per 1000. Most of death cases (89%) were Italians (p < 0.02) and mainly affected by pulmonary tuberculosis (PTB). CONCLUSIONS: In Tuscany, tuberculosis is still a health concern in terms of both morbidity and mortality.

Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Real-World Analysis of Survival and Clinical Events in a Cohort of Italian Perinatally HIV-1 Infected Children From 2001 to 2018.

Background: Combined antiretroviral therapy (cART) has been associated with a steep decrease in mortality and morbidity in HIV-1 infected children. New antiretroviral molecules and drug classes have been developed and the management of HIV-infected children has improved, but recent data on survival are limited. Methods: An observational retrospective study investigating changes in mortality and morbidity was conducted on 1,091 perinatally HIV-1 infected children enrolled in the Italian Register for HIV Infection in Children and followed-up from 2001 to 2018. Results: Three hundred and fifty-four (32%) AIDS events and 26 (2%) deaths occurred overtime. Mortality rates decreased from 0.4/100 person-years in 2001-2006 to 0.27/100 person-years in 2007-2012 and 0.07/100 person-years in 2013-2018. Notably, 92% of the dead children were born in Italy, but only 50% were followed-up since birth or within three months of age. Seventy three percent of children had started cART at age ≥6 months; 23% were treated for <30 days before death. B and C clinical events progressively decreased (P < 0.0001). Opportunistic infections significantly decreased over time, but still were the most common events in all the periods (6.76/100 person-years in 2013-2018). In the last period, severe bacterial infections were the most common ones. Cancer rates were 0.07/100; 0.17/100; 0.07/100 person-years in the three periods, respectively. Conclusions: Progressive reductions both in mortality and in rates of class B and C clinical events and OIs have been observed during the cART era. However, deaths were still registered; more than half of dead children were enrolled after birth and had belatedly started cART.

Tear Film Characteristics During Wear of Daily Disposable Contact Lenses.

PURPOSE: To evaluate changes induced over time by three daily disposable (DD) contact lenses on tear meniscus height (TMH), pre-lens non-invasive break-up time (pre-lens NIBUT), tear film osmolarity (TO) and objective quality of vision (OQV). PATIENTS AND METHODS: Forty-six subjects enrolled in this prospective open-label unmasked non-randomized simultaneous comparative cross-over study. For the first week of the study, subjects wore a nesofilcon A lens in the right eye and a delefilcon A lens in the left eye. After 3 days of washout, for the second week, subjects wore a nesofilcon A lens in the left eye and a stenfilcon A lens in the right eye. TMH, pre-lens NIBUT, TO and OQV were measured before contact lens fitting and for each contact lens combination on day 1 at 20 minutes and on day 7 after ≥8 hours of wear. OQV measurement included the changes of objective scatter index (OSI), the stability index (SI) and the fluctuation index (FI) calculated in a range of time of 20 s from a blink. RESULTS: TMH was unchanged at 20 minutes wear of all lenses but was significantly reduced after 8 or more hours wear (on day 7) of delefilcon A and stenfilcon A, respectively. Pre-lens NIBUT was significantly reduced with all lenses, while no significant change in TO was observed with any lens. SI and FI increased significantly for all lenses at both wear times. CONCLUSION: While the presence of any contact lens on the eye challenges the tear film, nesofilcon A contact lenses, despite their high water content, compared to delefilcon A and stenfilcon A contact lenses, showed a lower overall effect. We speculate that superior tear film behavior while wearing nesofilcon A lenses may translate to improved subjective comfort, but this remains to be evaluated.

Infectious Diseases in Internationally Adopted Children and Intercountry Discrepancies Among Screening Protocols, A Narrative Review.

Internationally adopted children (IAC) require thorough health assessments at time of arrival in the host country. As these children are at higher risk for infectious diseases, such as gastrointestinal parasites, tuberculosis, hepatitis, syphilis, and human immunodeficiency virus, early diagnosis of infectious diseases is fundamental for the optimal management of the child and, also, to reduce the risk of transmission to the adopting community. Comparative analysis of the screening protocols adopted in Europe, the United States, and Canada revealed different approaches to the adopted children. A homogeneous and internationally shared standard of care in the management of IAC should be provided.

Updated Guidelines for the Management of Acute Otitis Media in Children by the Italian Society of Pediatrics: Diagnosis.

BACKGROUND: In recent years, new progress has been made regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society therefore decided to issue an update to the previous guidelines published in 2010. METHODS: Literature searches were conducted on MEDLINE by Pubmed, including studies in children, in English or Italian, published between January 1, 2010, and December 31, 2018. The quality of the included studies was assessed using the grading of recommendations, assessment, development and evaluations (GRADE) methodology. In particular, the quality of the systematic reviews was evaluated using the AMSTAR 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts. RESULTS: The diagnosis of AOM is based on acute clinical symptoms and otoscopic evidence; alternatively, the presence of otorrhea associated with spontaneous tympanic membrane perforation allows the AOM diagnosis. The diagnosis of AOM must be certain and the use of a pneumatic otoscope is of fundamental importance. As an alternative to the pneumatic otoscope, pediatricians can use a static otoscope and a tympanometer. To objectively establish the severity of the episode for the formulation of a correct treatment program, an AOM severity scoring system taking into account clinical signs and otoscopic findings was developed. CONCLUSIONS: The diagnosis of AOM is clinical and requires the introduction of specific medical training programs. The use of pneumatic otoscopes must be promoted, as they are not sufficiently commonly used in routine practice in Italy.

Updated Guidelines for the Management of Acute Otitis Media in Children by the Italian Society of Pediatrics: diagnosis

In recent years, new progress has been made regarding the diagnosis, treatment and prevention of acute otitis media (AOM). The Italian Pediatric Society therefore decided to issue an update to the previous guidelines published in 2010. Literature searches were conducted on MEDLINE by Pubmed, including studies in children, in English or Italian, published between January 1, 2010, and December 31, 2018. The quality of the included studies was assessed using the grading of recommendations, assessment, development and evaluations (GRADE) methodology. In particular, the quality of the systematic reviews was evaluated using the AMSTAR 2 appraisal tool. The guidelines were formulated using the GRADE methodology by a multidisciplinary panel of experts. The diagnosis of AOM is based on acute clinical symptoms and otoscopic evidence; alternatively, the presence of otorrhea associated with spontaneous tympanic membrane perforation allows the AOM diagnosis. The diagnosis of AOM must be certain and the use of a pneumatic otoscope is of fundamental importance. As an alternative to the pneumatic otoscope, pediatricians can use a static otoscope and a tympanometer. To objectively establish the severity of the episode for the formulation of a correct treatment program, an AOM severity scoring system taking into account clinical signs and otoscopic findings was developed.The diagnosis of AOM is clinical and requires the introduction of specific medical training programs. The use of pneumatic otoscopes must be promoted, as they are not sufficiently commonly used in routine practice in Italy.

Omalizumab and mepolizumab in the landscape of biological therapy for severe asthma in children: how to choose?

Severe asthma has a substantial epidemiological impact on children and biological treatments can be an option to take into account, as they target specific molecules and pathways involved in its pathogenesis. Modern medicine is continuously and progressively oriented towards tailored treatments designed specifically for the pathology patterns observed in individual patients and identified as endotypes with associated biomarkers. In this regard, biologic treatments in asthma are one of the best examples. Among the biological drugs currently available, omalizumab is the one with the greatest amount of data on efficacy and safety, and the one we have more real-life clinical experience with. However, mepolizumab will likely be accessible soon globally for clinical use. Moreover, research on biological drugs for the treatment of severe asthma is expanding rapidly, with some molecules currently used in adult patients that could be registered also for pediatric use and new molecules that could be available in the future. On the other hand, due to this potential abundance of therapeutic options, new criteria could become necessary to guide clinicians through an evidence-based choice between omalizumab and these new drugs. For the same reason, more data collected specifically from pediatric clinical trials are necessary. In this review we aim to analyze the factors that could help clinicians make their choice and to highlight the unmet need for a more evidence-based choice.