Results from evaporation tests to support the MWTF heat removal system design

An experimental tests program was conducted to measure the evaporative heat removal from the surface of a tank of simulated waste. The results contained in this report constitute definition design data for the latest heat removal function of the MWTF primary ventilation system

Thermal response of a can handling unit (CHU) to a postulated plutonium hydride burn

A series of analyses were performed to support the design of the Can Handling Unit (CHU). The subject analyses focused on determining the time to repressurize a subatmospheric storage can containing plutonium metal versus the initial hole size and the transient thermal response to a postulated chemical reaction of 150 grams of plutonium hydride. Limiting the amount of gaseous reactants either by inerting the CHU or using a very small hole size for the initial opening appears to be a viable method of controlling the rate of the exothermic chemical reactions and system temperatures

Tank 241-C-106 Sluicing Evaluation

The Process Engineering Analyses group performed a Thermal evaluation of the Project W-320 retrieval process. The objective of this study was to characterize the thermal response of the tank 241-C-106 waste during the sluicing operation and to define operating limits (defined with measurable tank data), which will maintain the waste subcooling required by the operational controls

Repurposing of plasminogen: An orphan medicinal product suitable for SARS-CoV-2 inhalable therapeutics

The SARS-CoV-2 infection is associated with pulmonary coagulopathy, which determines the deposition of fibrin in the air spaces and lung parenchyma. The resulting lung lesions compromise patient pulmonary function and increase mortality, or end in permanent lung damage for those who have recovered from the COVID-19 disease. Therefore, local pulmonary fibrinolysis can be efficacious in degrading pre-existing fibrin clots and reducing the conversion of lung lesions into lasting scars. Plasminogen is considered a key player in fibrinolysis processes, and in view of a bench-to-bedside translation, we focused on the aerosolization of an orphan medicinal product (OMP) for ligneous conjunctivitis: human plasminogen (PLG-OMP) eye drops. As such, the sterile and preservative-free solution guarantees the pharmaceutical quality of GMP production and meets the Ph. Eur. requirements of liquid preparations for nebulization. PLG-OMP aerosolization was evaluated both from technological and stability viewpoints, after being submitted to either jet or ultrasonic nebulization. Jet nebulization resulted in a more efficient delivery of an aerosol suitable for pulmonary deposition. The biochemical investigation highlighted substantial protein integrity maintenance with the percentage of native plasminogen band > 90%, in accordance with the quality specifications of PLG-OMP. In a coherent way, the specific activity of plasminogen is maintained within the range 4.8–5.6 IU/mg (PLG-OMP pre-nebulization: 5.0 IU/mg). This is the first study that focuses on the technological and biochemical aspects of aerosolized plasminogen, which could affect both treatment efficacy and clinical dosage delivery. Increasing evidence for the need of local fibrinolytic therapy could merge with the availability of PLG-OMP as an easy handling solution, readily aerosolizable for a fast translation into an extended clinical efficacy assessment in COVID-19 patients

Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation

Near-infrared spectroscopy estimation of combined skeletal muscle oxidative capacity and O2 diffusion capacity in humans

The final steps of the O2 cascade during exercise depend on the product of the microvascular-tointramyocyte PO2 difference and muscle O2 diffusing capacity (DmO2). Non-invasive methods to determine DmO2 in humans are currently unavailable. Muscle oxygen uptake (mVO2) recovery rate constant (k), measured by near-infrared spectroscopy (NIRS) using intermittent arterial occlusions, is associated with muscle oxidative capacity in vivo. We reasoned that k would be limited by DmO2 when muscle oxygenation is low (kLOW), and hypothesized that: i) k in well-oxygenated muscle (kHIGH) is associated with maximal O2 flux in fiber bundles; and ii) Δk (kHIGH-kLOW) is associated with capillary density (CD). Vastus lateralis k was measured in 12 participants using NIRS after moderate exercise. The timing and duration of arterial occlusions were manipulated to maintain tissue saturation index (TSI) within a 10% range either below (LOW) or above (HIGH) half-maximal desaturation, assessed during sustained arterial occlusion. Maximal O2 flux in phosphorylating state was 37.7±10.6 pmol·s−1·mg−1 (~5.8 ml·min−1·100g−1). CD ranged 348 to 586 mm-2. kHIGH was greater than kLOW (3.15±0.45 vs 1.56±0.79 min-1, p\u3c0.001). Maximal O2 flux was correlated with kHIGH (r=0.80, p=0.002) but not kLOW (r=-0.10, p=0.755). Δk ranged -0.26 to -2.55 min-1, and correlated with CD (r=- 0.68, p=0.015). mVO2 k reflects muscle oxidative capacity only in well-oxygenated muscle. Δk, the difference in k between well- and poorly-oxygenated muscle, was associated with CD, a mediator of DmO2. Assessment of muscle k and Δk using NIRS provides a non-invasive window on muscle oxidative and O2 diffusing capacity

Robot-mediated overground gait training for transfemoral amputees with a powered bilateral hip orthosis: a pilot study

Background: Transfemoral amputation is a serious intervention that alters the locomotion pattern, leading to secondary disorders and reduced quality of life. The outcomes of current gait rehabilitation for TFAs seem to be highly dependent on factors such as the duration and intensity of the treatment and the age or etiology of the patient. Although the use of robotic assistance for prosthetic gait rehabilitation has been limited, robotic technologies have demonstrated positive rehabilitative effects for other mobility disorders and may thus offer a promising solution for the restoration of healthy gait in TFAs. This study therefore explored the feasibility of using a bilateral powered hip orthosis (APO) to train the gait of community-ambulating TFAs and the effects on their walking abilities. Methods: Seven participants (46–71 years old with different mobility levels) were included in the study and assigned to one of two groups (namely Symmetry and Speed groups) according to their prosthesis type, mobility level, and prior experience with the exoskeleton. Each participant engaged in a maximum of 12 sessions, divided into one Enrollment session, one Tuning session, two Assessment sessions (conducted before and after the training program), and eight Training sessions, each consisting of 20 minutes of robotically assisted overground walking combined with additional tasks. The two groups were assisted by different torque-phase profiles, aiming at improving symmetry for the Symmetry group and at maximizing the net power transferred by the APO for the Speed group. During the Assessment sessions, participants performed two 6-min walking tests (6mWTs), one with (Exo) and one without (NoExo) the exoskeleton, at either maximal (Symmetry group) or self-selected (Speed group) speed. Spatio-temporal gait parameters were recorded by commercial measurement equipment as well as by the APO sensors, and metabolic efficiency was estimated via the Cost of Transport (CoT). Additionally, kinetic and kinematic data were recorded before and after treatment in the NoExo condition. Results: The one-month training protocol was found to be a feasible strategy to train TFAs, as all participants smoothly completed the clinical protocol with no relevant mechanical failures of the APO. The walking performance of participants improved after the training. During the 6mWT in NoExo, participants in the Symmetry and Speed groups respectively walked 17.4% and 11.7% farther and increased walking speed by 13.7% and 17.9%, with improved temporal and spatial symmetry for the former group and decreased energetic expenditure for the latter. Gait analysis showed that ankle power, step width, and hip kinematics were modified towards healthy reference levels in both groups. In the Exo condition metabolic efficiency was reduced by 3% for the Symmetry group and more than 20% for the Speed group. Conclusions: This study presents the first pilot study to apply a wearable robotic orthosis (APO) to assist TFAs in an overground gait rehabilitation program. The proposed APO-assisted training program was demonstrated as a feasible strategy to train TFAs in a rehabilitation setting. Subjects improved their walking abilities, although further studies are required to evaluate the effectiveness of the APO compared to other gait interventions. Future protocols will include a lighter version of the APO along with optimized assistive strategies

Multiplanar strain quantification for assessment of right ventricular dysfunction and non-ischemic fibrosis among patients with ischemic mitral regurgitation

Background: Ischemic mitral regurgitation (iMR) predisposes to right ventricular (RV) pressure and volume overload, providing a nidus for RV dysfunction (RVDYS) and non-ischemic fibrosis (NIF). Echocardiography (echo) is widely used to assess iMR, but performance of different indices as markers of RVDYS and NIF is unknown. Methods: iMR patients prospectively underwent echo and cardiac magnetic resonance (CMR) within 72 hours. Echo quantified iMR, assessed conventional RV indices (TAPSE, RV-S’, fractional area change [FAC]), and strain via speckle tracking in apical 4-chamber (global longitudinal strain [RV-GLS]) and parasternal long axis orientation (transverse strain). CMR volumetrically quantified RVEF, and assessed ischemic pattern myocardial infarction (MI) and septal NIF. Results: 73 iMR patients were studied; 36% had RVDYS (EF<50%) on CMR among whom LVEF was lower, PA systolic pressure higher, and MI size larger (all p<0.05). CMR RVEF was paralleled by echo results; correlations were highest for RV-GLS (r = 0.73) and lowest for RV-S’ (r = 0.43; all p<0.001). RVDYS patients more often had CMR-evidenced NIF (54% vs. 7%; p<0.001). Whereas all RV indices were lower among NIF-affected patients (all p≤0.006), percent change was largest for transverse strain (48.3%). CMR RVEF was independently associated with RV-GLS (partial r = 0.57, p<0.001) and transverse strain (r = 0.38, p = 0.002) (R = 0.78, p<0.001). Overall diagnostic performance of RV-GLS and transverse strain were similar (AUC = 0.93[0.87–0.99]|0.91[0.84–0.99], both p<0.001), and yielded near equivalent sensitivity and specificity (85%|83% and 80%|79% respectively). Conclusion: Compared to conventional echo indices, RV strain parameters yield stronger correlation with CMR-defined RVEF and potentially constitute better markers of CMR-evidenced NIF in iMR

Lower-limb amputees can reduce the energy cost of walking when assisted by an Active Pelvis Orthosis

Exoskeletons could compete with active prostheses as effective aids to reduce the increased metabolic demands faced by lower-limb amputees during locomotion. However, little evidence of their efficacy with amputees has been provided so far. In this paper, a portable hip exoskeleton has been tested with seven healthy subjects and two transfemoral amputees, with the final goal to verify whether a hip flexion-extension assistance could be effective in reducing the metabolic cost of walking. The metabolic power of the participants was estimated through indirect calorimetry during alternated repetitions of three treadmill-based walking conditions: without the exoskeleton (NoExo), with the exoskeleton in zero-torque mode (ExoTM) and with the exoskeleton providing hip flexion-extension assistance (ExoAM). The results showed that the exoskeleton reduced the net metabolic power of the two amputees in ExoAM with respect to NoExo, by 5.0% and 3.4%. With healthy subjects, a 5.5±3.1% average reduction in the metabolic power was observed during ExoAM compared to ExoTM (differences were not statistically significant), whereas ExoAM required 3.9±3.0% higher metabolic power than NoExo (differences were not statistically significant). These results provide initial evidence of the potential of exoskeletal technologies for assisting lower-limb amputees, thereby paving the way for further experimentations