Many drugs that show potential in animal models of glioblastoma (GBM) fail to translate to the clinic, contributing to a paucity of new therapeutic options. In addition, animal model development ...often includes histologic assessment, but multiparametric/multimodality imaging is rarely included despite increasing utilization in patient cancer management. This study developed an intracranial recurrent, drug-resistant, human-derived glioblastoma tumor in Sprague-Dawley
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knockout rat and was characterized both histologically and using multiparametric/multimodality neuroimaging. Hybrid
F-fluoroethyltyrosine positron emission tomography and magnetic resonance imaging, including chemical exchange saturation transfer (
F-FET PET/CEST MRI), was performed for full tumor viability determination and characterization. Histological analysis demonstrated human-like GBM features of the intracranially implanted tumor, with rapid tumor cell proliferation (Ki67 positivity: 30.5 ± 7.8%) and neovascular heterogeneity (von Willebrand factor VIII:1.8 to 5.0% positivity). Early serial MRI followed by simultaneous
F-FET PET/CEST MRI demonstrated consistent, predictable tumor growth, with exponential tumor growth most evident between days 35 and 49 post-implantation. In a second, larger cohort of rats,
F-FET PET/CEST MRI was performed in mature tumors (day 49 post-implantation) for biomarker determination, followed by evaluation of single and combination therapy as part of the model development and validation. The mean percentage of the injected dose per mL of
F-FET PET correlated with the mean %CEST (r = 0.67, P < 0.05), but there was also a qualitative difference in hot spot location within the tumor, indicating complementary information regarding the tumor cell demand for amino acids and tumor intracellular mobile phase protein levels. Finally, the use of this glioblastoma animal model for therapy assessment was validated by its increased overall survival after treatment with combination therapy (temozolomide and idasanutlin) (P < 0.001). Our findings hold promise for a more accurate tumor viability determination and novel therapy assessment
in a recently developed, reproducible, intracranial, PDX GBM.
The present paper describes a holistic energy efficient retrofit of low income multiple social housing located in Athens, Greece. A holistic analysis was conducted in order to determine the optimum ...retrofit plan that includes innovative and state of the art commercially available technologies, passive techniques as well as renewable energy sources, aiming to reduce its energy consumption and carbon footprint, improve indoor environmental conditions and be cost effective at the same time. An extensive experimental campaign including air leakage measurements, thermal imaging, energy consumption and indoor environmental quality measurements was conducted before and after the implementation of the retrofit. In addition, advanced building simulation, occupant surveys and socioeconomic analyses were performed in order to evaluate the impact of the retrofit and estimate specific performance indicators.
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Abstract
Thermo-physiological models represent a valid approach for the study of person-environment energy interactions and constitute an alternative and promising methodology for the study of ...comfort in all those cases in which the Fanger’s statistical model is not applicable. By dividing the body into several segments, and these into several nodes, including physiological variables among the inputs and detailing the representation of clothing, these models are better suited to application in the healthcare sector, as they can take into account pathological states that alter physiological responses (patients) and specific types of clothing and activities (medical staff). In this work, the Tanabe 65 MN model, implemented in the ABICS opensource software, has been used to identify the thermo-active zones in which sweating occurs on at least one section of the body for a person of the medical staff. A parametric analysis was developed by varying the ambient temperature (20 - 36 °C), the relative humidity (40 - 60%), the metabolic rate (1.5 - 2.0 met) and considering a young subject (30 years) and an older one (60 years). These zones were identified on charts correlating the skin temperature to the ambient one. In both cases, a similar trend is observed: the average temperature of the skin, at which sweating occurs, increases as the ambient temperature grows and on average this mechanism is activated for lower skin temperatures in the case of the older individual.
Abstract
Digitalization is sweeping the world of buildings. Notably, the use of machine and deep learning techniques to develop buildings’ digital twins is becoming crucial to foster the energy ...transition of the construction sector and a sustainable urban growth. Digital twins can ensure a user-friendly, fast and reliable prediction of building energy loads and demands, thereby enabling a comprehensive optimization of planning, design and operation. Accordingly, this study investigates machine learning techniques to predict heating loads of a building in Rome (Italy, Mediterranean conditions, “Csa” climate in the Köppen and Geiger classification) and in Berlin (Germany, European backcountry, “Cfb”). Firstly, the real building, located in Benevento, is used to develop the artificial neural networks (ANNs), then implemented in MATLAB® to achieve meta-models of building energy behavior. NARX (nonlinear autoregressive model with exogenous inputs) networks are used and trained based on simulated data, provided by the well-known building simulation tool EnergyPlus using the software DesignBuilder® as interface. The meta-model inputs are related to weather conditions, while the required outputs concern the thermal energy load for space heating. The analysis is performed with reference to annual forecasts of energy demands. In all cases, the ANNs architecture is optimized to achieve the best fitness with EnergyPlus outputs. The results show that machine learning can be a precious and reliable tool to support energy design and operation of different buildings in different climates. Nonetheless, the meta-modeling procedure needs to be properly conducted by experts to set suitable frameworks and hyperparameter values of the ANNs, as well as to achieve a right and comprehensive interpretation of the results.
IV methylprednisolone (IVMP) has been used to treat relapses in patients with relapsing-remitting (RR) MS, but its effect on disease progression is not known. Furthermore, there are no data on the ...impact of IVMP on T1 black holes or whole-brain atrophy.
To determine the effect of IVMP on MRI measures of the destructive pathology in patients with RR-MS and secondarily to determine the effect of IVMP on disability progression in patients with RR-MS.
The authors conducted a randomized, controlled, single-blind, phase II clinical trial of IVMP in patients with RR-MS. Eighty-eight patients with RR-MS with baseline Expanded Disability Status Scale (EDSS) scores of < or =5.5 were randomly assigned to regular pulses of IVMP (1 g/day for 5 days with an oral prednisone taper) or IVMP at the same dose schedule only for relapses (IVMP for relapses) and followed without other disease-modifying drug therapy for 5 years. Pulsed IVMP was given every 4 months for 3 years and then every 6 months for the subsequent 2 years. Patients had quantitative cranial MRI scans at study entry and after 5 years and standardized clinical assessments every 4 to 6 months.
Eighty-one of 88 patients completed the trial as planned, and treatment was well tolerated. Baseline demographic, clinical, and MRI measures were well matched in the two study arms. Patients on the pulsed IVMP arm received more MP than patients on the control arm of the study (p < 0.0001). Mean change in T1 black hole volume favored pulsed IVMP therapy (+1.3 vs +5.2 mL; p < 0.0001), as did mean change in brain parenchymal volume (+2.6 vs -74.5 mL; p = 0.003). There was no significant difference between treatment arms in the change in T2 volume or annual relapse rate during the study. However, there was significantly more EDSS score worsening in the control group, receiving IVMP only for relapses. There was a 32.2% reduction (p </= 0.0001) in the probability of sustained EDSS score worsening in the pulsed MP arm compared with the relapse treatment arm. At the end of the study, EDSS was better in the pulsed MP group (1.7 vs 3.4; p < 0.0001). Prolonged treatment with pulsed IVMP was safe and well tolerated; only two patients dropped out for toxic side effects over 5 years.
In patients with RR-MS, treatment with pulses of IVMP slows development of T1 black holes, prevents or delays whole-brain atrophy, and prevents or delays disability progression. A phase III study of IVMP pulses is warranted.
The proposed paper is focused on some of the main conceptions, design criteria and expected energy performance of a new nZEB built in Benevento, a middle-size city of South Italy with typical ...Mediterranean climate. It is the result of an Italian research project - SMARTCASE - promoted under the umbrella of the European Regional Development Fund. The paper discusses the results of the wintertime monitoring campaign. Measurements on building envelope are shown as well as monitoring of energy uses and indoor microclimatic conditions. The discussion about the hourly energy balance evidences the effectiveness of selected solutions to reach the zero objective also during the winter and to evaluate the incidence of PV-production.
Indoor overheating risk and increased energy demand for cooling are becoming more and more frequent in the building sector of the Mediterranean area. In detail, for the reduction of the energy ...consumption of educational buildings, characterized by high endogenous gains, the particular boundary conditions affecting their use should be taken in consideration, and thus schedules of occupancy, wide necessity of air-changes for air quality. This paper, with reference to a case study, proposes deep investigations aimed at optimizing the annual energy performance of an educational building of the University of Sannio, located in the Southern Italy. A numerical model of the building has been designed and validated according to monitored data. Starting from the present scenario, after a complete refurbishment of the building envelope, the potentialities of several typologies of green roofs - by considering also the implementation of the adaptive approach in the comfort standard - have been tested. The scope is the optimization of the energy demand for the annual microclimatic control, by avoiding an energy-intensive operation of the air-conditioning devices during the warm season.
OBJECTIVE (a) To establish whether the cognitive decline of the early phase of relapsing-remitting multiple sclerosis depends on the progression of the burden of disease, or on the loss of brain ...parenchyma, or is influenced by both; (b) to monitor the loss of brain parenchyma in the early phase of the disease; and (c) to examine its possible relation with the progression of physical disability. METHODS For 2 years 53 patients with clinically definite relapsing-remitting multiple sclerosis with disease duration 1–5 years and expanded disability status scale⩽5.0 at baseline were monitored. The neuropsychological performances, the psychological functioning, the neurological impairment, and the disability have been assessed at baseline and after 2 years. Patients also underwent PD/T2 and T1 weighted brain MRI. T2 and T1 lesion volumes were measured by a semiautomatic technique. Quantification of brain parenchymal volumes was obtained using a highly reproducible computerised interactive program. The relation between cognitive impairment and MRI findings has been investigated by partial correlation and stepwise multiple regression analyses excluding the effects of age, education, anxiety, depression, and total days of steroid use. RESULTS In the 2 years of the study the mean change for T2 and T1 lesion volumes and brain parenchymal volumes were +1.7 ml (95% confidence interval (95% CI) 1.3–2.2, p=0.005, (29.8%); +0.2 ml, 95% CI 0.15–0.26, p=0.004, (25%); and –32.3 ml, 95% CI 24.2–42.3, p<0.0001, (2.7%), respectively. Overall, 14 patients (26.4%) were judged to be cognitively impaired at baseline and 28 (52.8%) at the end of the follow up. Of the 18 neuropsychological tests and subtests employed in the study, patients with multiple sclerosis failed 5.8 (SD 2.3) tests at the baseline and 8.4 (SD 2.9) (p<0.0001) tests at the end of the study. When the cognitive changes were examined in individual patients, five (9.4%) of them were considered cognitively improved, 33 (62.3%) remained stable, and 15 (28.3%) worsened over 2 years. T2 and T1 volume changes in improved, stable, and worsened patients did not show any significant difference, whereas brain parenchymal volume decrease in cognitively worsened patients was significantly greater (−66 ml (5.4%), 95% CI 37–108.9, p=0.0031). The cognitive impairment was independently predicted over 2 years only by the change of brain parenchymal volumes (R=0.51, p=0.0003). Ten patients (18.9%), who worsened by one or more points in the EDSS during the follow up period had significant decreases in brain parenchymal volumes (−99 ml (8%), 95% CI 47.6–182.3, p=0.005). At the end of the study the loss of brain parenchyma correlated significantly with change in EDSS (r= 0.59, p<0.0001). CONCLUSIONS In the early phase of relapsing-remitting multiple sclerosis the cognitive deterioration relies more on the development of brain parenchymal volume atrophy than on the extent of burden of disease in the brain. The loss of brain parenchymal volume underlies the progressive accumulation of physical disability from the initial phase of the disease, which becomes more demonstrable only if studied with longer observation periods. Probably, the main pathological substrate of brain atrophy in the early stage of the disease is early axonal loss, which causes the progression of neurological deficits and the development of cognitive impairment. These data support the debated opinion that disease modifying therapy should be initiated as early as possible.
CMOS pixel sensors are foreseen to equip the vertex detector (called PXL) of the upgraded inner tracking system of the STAR experiment at RHIC. The sensors (called ULTIMATE) are being designed and ...their architecture is being optimized for the PXL specifications, extrapolating from the MIMOSA-26 sensor realized for the EUDET beam telescope.
The paper gives an overview of the ULTIMATE sensor specifications and of the adaptation of its forerunner, MIMOSA-26, to the PXL specifications.
One of the main changes between MIMOSA-26 and ULTIMATE is the use of a high resistivity epitaxial layer. Recent performance assessments obtained with MIMOSA-26 sensors manufactured on such an epitaxial layer are presented, as well as results of beam tests obtained with a prototype probing improved versions of the MIMOSA-26 pixel design. They show drastic improvements of the pixel signal-to-noise ratio and of the sensor radiation tolerance with respect to the performances achieved with a standard, i.e. low resistivity, layer.
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The structure, morphology and composition of conversion coatings grown in stannate bath on pure Mg were studied using potential–time, polarization curves, X-ray diffraction, scanning electron ...microscopy and photocurrent spectroscopy. The coating is manly constituted by crystalline magnesium–tin hydroxide, whose morphology and distribution depends on the conversion bath composition and temperature. The photoelectrochemical investigation allowed to estimate the band gap value of MgSn(OH)
6 and flat band potential. A sketch of the metal/passive film/electrolyte junction formed during conversion on the metal substrate is reported to account for the overall photoelectrochemical behaviour.
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