Neuropsychological long‐term sequelae after posterior fossa tumour resection during childhood

The importance of the cerebellum for non‐motor functions is becoming more and more evident. The influence on cognitive functions from acquired cerebellar lesions during childhood, however, is not well known. We present follow‐up data from 24 patients, who were operated upon during childhood for benign cerebellar tumours. The benign histology of these tumours required neither radiotherapy nor chemotherapy. Post‐operatively, these children were of normal intelligence with a mean IQ of 99.1, performance intelligence quotient (PIQ) of 101.3 and verbal intelligence quotient (VIQ) of 96.8. However, 57% of patients showed abnormalities in subtesting. In addition, more extensive neuropsychological testing revealed significant problems for attention, memory, processing speed and interference. Visuo‐constructive problems were marked for copying the Rey figure, but less pronounced for recall of the figure. Verbal fluency was more affected than design fluency. Behavioural deficits could be detected in 33% of patients. Attention deficit problems were marked in 12.5%, whereas others demonstrated psychiatric symptoms such as mutism, addiction problems, anorexia, uncontrolled temper tantrums and phobia. Age at tumour operation and size of tumour had no influence on outcome. Vermis involvement was related to an increase in neuropsychological and psychiatric problems. The observation that patients with left‐sided cerebellar tumours were more affected than patients with right‐sided tumours is probably also influenced by a more pronounced vermian involvement in the former group. In summary, this study confirms the importance of the cerebellum for cognitive development and points to the necessity of careful follow‐up for these children to provide them with the necessary help to achieve full integration into professional lif

Stability Program in Dendritic Cell Vaccines: A “Real-World” Experience in the Immuno-Gene Therapy Factory of Romagna Cancer Center

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute. The DC-based vaccine is prepared via CD14+ monocyte differentiation. A fresh dose of 10 million DCs is administered to the patient, while the remaining DCs are aliquoted, frozen, and stored in nitrogen vapor for subsequent treatment doses. To evaluate the maintenance of quality parameters and to establish a shelf life of frozen vaccine aliquots, a stability program was developed. Several parameters of the DC final product at 0, 6, 12, 18, and 24 months were evaluated. Our results reveal that after 24 months of storage in nitrogen vapor, the cell viability is in a range between 82% and 99%, the expression of maturation markers remains inside the criteria for batch release, the sterility tests are compliant, and the cell costimulatory capacity unchanged. Thus, the data collected demonstrate that freezing and thawing do not perturb the DC vaccine product maintaining over time its functional and quality characteristics

Integrating Multiple Research Methods to Unravel the Complexity of Human-Water Systems

Abstract: Predicting floods and droughts is essential to inform the development of policy in water management, climate change adaptation and disaster risk reduction. Yet, hydrological predictions are highly uncertain, while the frequency, severity and spatial distribution of extreme events are further complicated by the increasing impact of human activities on the water cycle. In this commentary, we argue that four main aspects characterizing the complexity of human‐water systems should be explicitly addressed: feedbacks, scales, tradeoffs and inequalities. We propose the integration of multiple research methods as a way to cope with complexity and develop policy‐relevant science

Needs and gaps in optical underwater technologies and methods for the investigation of marine animal forest 3D-structural complexity

Marine animal forests are benthic communities dominated by sessile suspension feeders (such as sponges, corals, and bivalves) able to generate three-dimensional (3D) frameworks with high structural complexity. The biodiversity and functioning of marine animal forests are strictly related to their 3D complexity. The present paper aims at providing new perspectives in underwater optical surveys. Starting from the current gaps in data collection and analysis that critically limit the study and conservation of marine animal forests, we discuss the main technological and methodological needs for the investigation of their 3D structural complexity at different spatial and temporal scales. Despite recent technological advances, it seems that several issues in data acquisition and processing need to be solved, to properly map the different benthic habitats in which marine animal forests are present, their health status and to measure structural complexity. Proper precision and accuracy should be chosen and assured in relation to the biological and ecological processes investigated. Besides, standardized methods and protocols are strictly necessary to meet the FAIR (findability, accessibility, interoperability, and reusability) data principles for the stewardship of habitat mapping and biodiversity, biomass, and growth data

Nanoanalytical analysis of bisphosphonate-driven alterations of microcalcifications using a 3D hydrogel system and in vivo mouse model

Vascular calcification predicts atherosclerotic plaque rupture and cardiovascular events. Retrospective studies of women taking bisphosphonates (BiPs), a proposed therapy for vascular calcification, showed that BiPs paradoxically increased morbidity in patients with prior acute cardiovascular events but decreased mortality in event-free patients. Calcifying extracellular vesicles (EVs), released by cells within atherosclerotic plaques, aggregate and nucleate calcification. We hypothesized that BiPs block EV aggregation and modify existing mineral growth, potentially altering microcalcification morphology and the risk of plaque rupture. Three-dimensional (3D) collagen hydrogels incubated with calcifying EVs were used to mimic fibrous cap calcification in vitro, while an ApoE−/− mouse was used as a model of atherosclerosis in vivo. EV aggregation and formation of stress-inducing microcalcifications was imaged via scanning electron microscopy (SEM) and atomic force microscopy (AFM). In both models, BiP (ibandronate) treatment resulted in time-dependent changes in microcalcification size and mineral morphology, dependent on whether BiP treatment was initiated before or after the expected onset of microcalcification formation. Following BiP treatment at any time, microcalcifications formed in vitro were predicted to have an associated threefold decrease in fibrous cap tensile stress compared to untreated controls, estimated using finite element analysis (FEA). These findings support our hypothesis that BiPs alter EV-driven calcification. The study also confirmed that our 3D hydrogel is a viable platform to study EVmediated mineral nucleation and evaluate potential therapies for cardiovascular calcification

The Sardinia Radio Telescope . From a technological project to a radio observatory

Context. The Sardinia Radio Telescope (SRT) is the new 64 m dish operated by the Italian National Institute for Astrophysics (INAF). Its active surface, comprised of 1008 separate aluminium panels supported by electromechanical actuators, will allow us to observe at frequencies of up to 116 GHz. At the moment, three receivers, one per focal position, have been installed and tested: a 7-beam K-band receiver, a mono-feed C-band receiver, and a coaxial dual-feed L/P band receiver. The SRT was officially opened in September 2013, upon completion of its technical commissioning phase. In this paper, we provide an overview of the main science drivers for the SRT, describe the main outcomes from the scientific commissioning of the telescope, and discuss a set of observations demonstrating the scientific capabilities of the SRT. Aims: The scientific commissioning phase, carried out in the 2012-2015 period, proceeded in stages following the implementation and/or fine-tuning of advanced subsystems such as the active surface, the derotator, new releases of the acquisition software, etc. One of the main objectives of scientific commissioning was the identification of deficiencies in the instrumentation and/or in the telescope subsystems for further optimization. As a result, the overall telescope performance has been significantly improved. Methods: As part of the scientific commissioning activities, different observing modes were tested and validated, and the first astronomical observations were carried out to demonstrate the science capabilities of the SRT. In addition, we developed astronomer-oriented software tools to support future observers on site. In the following, we refer to the overall scientific commissioning and software development activities as astronomical validation. Results: The astronomical validation activities were prioritized based on technical readiness and scientific impact. The highest priority was to make the SRT available for joint observations as part of European networks. As a result, the SRT started to participate (in shared-risk mode) in European VLBI Network (EVN) and Large European Array for Pulsars (LEAP) observing sessions in early 2014. The validation of single-dish operations for the suite of SRT first light receivers and backends continued in the following year, and was concluded with the first call for shared-risk early-science observations issued at the end of 2015. As discussed in the paper, the SRT capabilities were tested (and optimized when possible) for several different observing modes: imaging, spectroscopy, pulsar timing, and transients

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening