Bio-inspired compensatory strategies for damage to flapping robotic propulsors.

Natural swimmers and flyers can fully recover from catastrophic propulsor damage by altering stroke mechanics: some fish can lose even 76% of their propulsive surface without loss of thrust. We consider applying these principles to enable robotic flapping propulsors to autonomously repair functionality. However, direct transference of these alterations from an organism to a robotic flapping propulsor may be suboptimal owing to irrelevant evolutionary pressures. Instead, we use machine learning techniques to compare these alterations with those optimal for a robotic system. We implement an online artificial evolution with hardware-in-the-loop, performing experimental evaluations with a flexible plate. To recoup thrust, the learned strategy increased amplitude, frequency and angle of attack (AOA) amplitude, and phase-shifted AOA by approximately 110°. Only amplitude increase is reported by most fish literature. When recovering side force, we find that force direction is correlated with AOA. No clear amplitude or frequency trend is found, whereas frequency increases in most insect literature. These results suggest that how mechanical flapping propulsors most efficiently adjust to damage may not align with natural swimmers and flyers.

Green synthesis of silver nanoparticles and its environmental sensor ability to some heavy metals.

This study marks a pioneering effort in utilizing Vachellia tortilis subsp. raddiana (Savi) Kyal. & Boatwr., (commonly known as acacia raddiana) leaves as both a reducing and stabilizing agent in the green "eco-friendly" synthesis of silver nanoparticles (AgNPs). The research aimed to optimize the AgNPs synthesis process by investigating the influence of pH, temperature, extract volume, and contact time on both the reaction rate and the resulting AgNPs' morphology as well as discuss the potential of AgNPs in detecting some heavy metals. Various characterization methods, such as UV-vis spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared spectroscopy (IR), Zeta sizer, EDAX, and transmitting electron microscopy (TEM), were used to thoroughly analyze the properties of the synthesized AgNPs. The XRD results verified the successful production of AgNPs with a crystallite size between 20 to 30 nm. SEM and TEM analyses revealed that the AgNPs are primarily spherical and rod-shaped, with sizes ranging from 8 to 41 nm. Significantly, the synthesis rate of AgNPs was notably higher in basic conditions (pH 10) at 70 °C. These results underscore the effectiveness of acacia raddiana as a source for sustainable AgNPs synthesis. The study also examined the AgNPs' ability to detect various heavy metal ions colorimetrically, including Hg2+, Cu2+, Pb2+, and Co2+. UV-Vis spectroscopy proved useful for this purpose. The color of AgNPs shifts from brownish-yellow to pale yellow, colorless, pale red, and reddish yellow when detecting Cu2+, Hg2+, Co2+, and Pb2+ ions, respectively. This change results in an alteration of the AgNPs' absorbance band, vanishing with Hg2+ and shifting from 423 to 352 nm, 438 nm, and 429 nm for Cu2+, Co2+, and Pb2+ ions, respectively. The AgNPs showed high sensitivity, with detection limits of 1.322 × 10-5 M, 1.37 × 10-7 M, 1.63 × 10-5 M, and 1.34 × 10-4 M for Hg2+, Cu2+, Pb2+, and Co2+, respectively. This study highlights the potential of using acacia raddiana for the eco-friendly synthesis of AgNPs and their effectiveness as environmental sensors for heavy metals, showcasing strong capabilities in colorimetric detection.

Inflammatory BCG adenitis associated with immune reconstitution following allogeneic haematopoietic stem cell transplant in infancy.

We describe four cases of a localized, granulomatous reaction to BCG including ipsilateral painful, suppurative lymphadenopathy associated with donor immune reconstitution following allogeneic haematopoietic stem cell transplant performed in infancy and preceded by uneventful, routine BCG immunisation. The management of the inflammatory disease in these cases with surgery, antimycobacterial chemotherapy and steroids, is discussed.

A dynamical model of oncotripsy by mechanical cell fatigue: selective cancer cell ablation by low-intensity pulsed ultrasound.

The method of oncotripsy, first proposed in Heyden & Ortiz (Heyden & Ortiz 2016 J. Mech. Phys. Solids 92, 164-175 (doi:10.1016/j.jmps.2016.04.016)), exploits aberrations in the material properties and morphology of cancerous cells in order to ablate them selectively by means of tuned low-intensity pulsed ultrasound. We propose the dynamical model of oncotripsy that follows as an application of cell dynamics, statistical mechanical theory of network elasticity and 'birth-death' kinetics to describe the processes of damage and repair of the cytoskeleton. We also develop a reduced dynamical model that approximates the three-dimensional dynamics of the cell and facilitates parametric studies, including sensitivity analysis and process optimization. We show that the dynamical model predicts-and provides a conceptual basis for understanding-the oncotripsy effect and other trends in the data of Mittelstein et al. (Mittelstein et al. 2019 Appl. Phys. Lett. 116, 013701 (doi:10.1063/1.5128627)), for cells in suspension, including the dependence of cell-death curves on cell and process parameters.

Phase I study of temsirolimus in combination with cetuximab in patients with advanced solid tumours.

BACKGROUND: Preclinical studies suggest synergistic antitumour effects of mammalian target of rapamycin (mTOR) inhibitor such as temsirolimus combined with anti-EGFR monoclonal antibody such as cetuximab. METHODS: Temsirolimus (T) and cetuximab (C) were combined and escalated in cohorts of patients with advanced or metastatic solid tumours, respectively from 15 to 25 mg and 150-250 mg/m2, until the maximum tolerated dose (MTD) was determined. Effort was made in the expansion cohort to enrol patients harbouring a molecular aberration in the human epidermal growth factor receptor (EGFR) and/or phosphoinositide 3-kinase (PI3K) pathways. Paired biopsies were optional to evaluate pathway modulation. RESULTS: Among 39 patients enrolled, three experienced dose-limiting toxicities (DLTs): pulmonary embolism (C200 + T20), stomatitis (C250 + T20) and acneiform rash (C250 + T25). The weekly C 250 mg/m2 and T 25 mg dose level was selected as the MTD. The most common treatment-related adverse events were: acneiform rash (97%), oral mucositis (82%), fatigue (59%), nausea (41%) and diarrhoea (36%). The median progression-free survival (PFS) and overall survival (OS) were respectively 2.0 months [95% CI: 1.8, 3.5] and 7.5 months [95% CI: 5.5, 11.9]. Among all patients, partial responses (PRs) and stable diseases (SDs) were observed in 2 (5.1%) and 18 patients (46.2%), respectively. The objective response rate (ORR) in patients with a molecular aberration was 2/14 (14%), versus 0/24 in those without molecular aberration. CONCLUSIONS: Combination of T + C showed significant but manageable toxicities. Due to modest clinical activity, further evaluation is not recommended. Molecular selection could potentially increase the objective response rate and should be implemented during drug development.

Shielding calculation and criticality safety analysis of spent fuel transportation cask in research reactors.

In this study, shielding calculation and criticality safety analysis were carried out for general material testing reactor (MTR) research reactors interim storage and relevant transportation cask. During these processes, three major terms were considered: source term, shielding, and criticality calculations. The Monte Carlo transport code MCNP5 was used for shielding calculation and criticality safety analysis and ORIGEN2.1 code for source term calculation. According to the results obtained, a cylindrical cask with body, top, and bottom thicknesses of 18, 13, and 13 cm, respectively, was accepted as the dual-purpose cask. Furthermore, it is shown that the total dose rates are below the normal transport criteria that meet the standards specified.

Nature of flow acceleration into a finite-sized orifice: steady and pulsatile flow studies on the flow convergence region using simultaneous ultrasound Doppler flow mapping and laser Doppler velocimetry.

OBJECTIVES: This study investigated the proximal centerline flow convergence region simultaneously by both color Doppler and laser Doppler velocimetry. BACKGROUND: Although numerous investigations have been performed to test the flow convergence method, to our knowledge there has yet been no experimental study using reference standard velocimetric techniques to define precisely the hydrodynamic factors involved in the accelerating flow region during steady and pulsatile flow. METHODS: Using an in vitro model that allows velocity measurements by laser Doppler velocimetry with simultaneous comparison with color Doppler results, we studied the centerline flow acceleration region proximal to orifices of various sizes (0.08 to 2.0 cm2). RESULTS: Agreement between theory and experimental velocities was good for large flow rates through small orifices only, and only at distances > 1.2 cm from the orifice. Changing the orifice shape from circular to slitlike produced no significant changes in velocity profiles. Constraining the proximal side walls caused a significant increase in proximal velocities at distances > 0.7 cm for the largest orifice only (2.0 cm2). Calculated flow rates agreed well with actual flow rates, with functional dependence on proximal distance and orifice size. Velocity profiles for pulsatile flow were similar to steady state flow profiles and could be integrated to calculate stroke volumes, which followed actual flow volumes well, although with general overestimation (y = 1.22x + 0.164, r = 0.92), most likely due to the use of all available proximal velocities. CONCLUSIONS: The accelerating proximal flow region responds to several hydrodynamic factors that can affect flow quantitation using the flow convergence method in the clinical situation.

Current status of flow convergence for clinical applications: is it a leaning tower of "PISA"?

Spatial appreciation of flow velocities using Doppler color flow mapping has led to quantitative evaluation of the zone of flow convergence proximal to a regurgitant orifice. Based on the theory of conservation of mass, geometric analysis, assuming a series of hemispheric shells of increasing velocity as flow converges on the orifice--the so-called proximal isovelocity surface area (PISA) effect--has yielded methods promising noninvasive measurement of regurgitant flow rate. When combined with conventional Doppler ultrasound to measure orifice velocity, regurgitant orifice area, the major predictor of regurgitation severity, can also be estimated. The high temporal resolution of color M-mode can be used to evaluate dynamic changes in orifice area, as seen in many pathologic conditions, which enhances our appreciation of the pathophysiology of regurgitation. The PISA methodology is potentially applicable to any restrictive orifice and has gained some credibility in the quantitative evaluation of other valve pathology, particularly mitral and tricuspid regurgitation, and in congenital heart disease. Although the current limitations of PISA estimates of regurgitation have tempered its introduction as a valuable clinical tool, considerable efforts in in vitro and clinical research have improved our understanding of the problems and limitations of the PISA methodology and provided a firm platform for continuing research into the accurate quantitative assessment of valve regurgitation and the expanding clinical role of quantitative Doppler color flow mapping.

Three-dimensional reconstruction of color Doppler flow convergence regions and regurgitant jets: an in vitro quantitative study.

OBJECTIVES: This study sought to investigate the applicability of a current implementation of a three-dimensional echocardiographic reconstruction method for color Doppler flow convergence and regurgitant jet imaging. BACKGROUND: Evaluation of regurgitant flow events, such as flow convergences or regurgitant jets, using two-dimensional imaging ultrasound color flow Doppler systems may not be robust enough to characterize these spatially complex events. METHODS: We studied two in vitro models using steady flow to optimize results. In the first constant-flow model, two different orifices were each mounted to produce flow convergences and free jets--a circular orifice and a rectangular orifice with orifice area of 0.24 cm(2). In another flow model, steady flows through a circular orifice were directed toward a curved surrounding wall to produce wall adherent jets. Video composite data of color Doppler flow images from both free jet and wall jet models were reconstructed and analyzed after computer-controlled 180 degrees rotational acquisition using a TomTec computer. RESULTS: For the free jet model there was an excellent relation between actual flow rates and three-dimensional regurgitant jet volumes for both circular and rectangular orifices (r = 0.99 and r = 0.98, respectively). However, the rectangular orifice produced larger jet volumes than the circular orifice, even at the same flow rates (p < 0.0001). Calculated flow rates by the hemispheric model using one axial measurement of the flow convergence isovelocity surface from two-dimensional color flow images underestimated actual flow rate by 35% for the circular orifice and by 44% for the rectangular orifice, whereas a hemielliptic method implemented using three axial measurements of the flow convergence zone derived using three-dimensional reconstruction correlated well with and underestimated actual flow rate to a lesser degree (22% for the circular orifice, 32% for the rectangular orifice). In the wall jet model, the jets were flattened against and spread along the wall and had reduced regurgitant jet volumes compared with free jets (p < 0.01). CONCLUSIONS: Three-dimensional reconstruction of flow imaged by color Doppler may add quantitative spatial information to aid computation methods that have been used for evaluating valvular regurgitation, especially where they related to complex geometric flow events.

Pituitary thyrotropic adenoma associated with congenital hypothyroidism. Report of two cases.

Two patients with congenital hypothyroidism and thyroid-stimulating hormone-secreting pituitary adenomas are described. Both patients had a history of long-standing, inadequately treated hypothyroidism accompanied by markedly elevated levels of serum thyroid-stimulating hormone. Pituitary tissue, obtained at autopsy in the first patient and at surgery in the second, disclosed a thyrotropic adenoma. Immunocytochemical studies with anti-thyroid-stimulating hormone antisera showed both tumors to be strongly immunoreactive. Such thyrotropic adenomas of the pituitary gland are presumed to occur as the result of protracted pituitary stimulation secondary to long-standing thyroid deficiency.

Effects of lymphokine-activated killer-cells on melanoma nodules maintained in 3-dimensional culture.

Lymphokine activated killer (LAK) cells were cocultivated from 2 to 6 days with WM266 metastatic melanoma cells maintained as nodules in organotypic culture. The LAK cells in suspension were allowed to deposit freely on the nodule surface from where they could infiltrate spontaneously into the nodules. Immunohistochemical studies were done to localize the LAK cells as well as electron microscopical observations for effector/target membrane contacts. Proliferation of the nodules was tested and also that of the LAK cells after coculturing using tritiated thymidine incorporation into DNA. Cell death was determined by arrest of thymidine incorporation and total nodule disintegration. Infiltration rate of LAK cells into the nodules was low: after coculturing 5% of the nodule cells were LAK cells. Although close membrane contacts and cytoplasmic fusions between effector and target cells leading to tumor cell apoptosis were observed, this direct cytolytic process seemed to be too infrequent for the induction of total nodule disintegration at day 6. Therefore, the indirect pathway to cytolysis might be predominant implying, among other cytokines, soluble TNF. On the other hand, LAK cell proliferation diminished strongly after coculturing (down to 11%) but the cytotoxicity was significantly enhanced (18% higher) suggesting an enhancement of differentiation. This might account for the peculiar efficacy of LAK cells on melanomas in vivo and it would be of interest to study this phenomenon further.

Chemotherapy-induced cardiotoxicity: current practice and prospects of prophylaxis.

Cardiotoxicity is a potential side effect of few chemotherapeutic agents. The anthracycline class of cytotoxic antibiotics are the most famous, but other chemotherapeutic agents can also cause serious cardiotoxicity and are not so well recognised. Examples include cyclophosphamide, ifosfamide, mitomycin and fluorouracil. Prediction and hence prophylaxis has always been a difficult task. Ideal monitoring techniques, upon which efficient prophylaxis depends, are yet to be determined. Current prophylaxis relies upon early detection of systolic and/or diastolic dysfunction. While somewhat useful, in some cases by the time defects are detected progression of chemotherapy-induced cardiomyopathy is beyond prevention. Prophylaxis would be much more efficient if a biochemical marker of myocardiocyte damage could be reliably used to stop further chemotherapy at the correct time before irreversible progressive 'macroscopic' damage becomes evident upon imaging. Work is currently progressing to identify the role of markers such as troponins and natriuretic peptides in this regard.

Nicotine self-administration in rats: estrous cycle effects, sex differences and nicotinic receptor binding.

RATIONALE: Research on smoking behavior and responsiveness to nicotine suggests that nicotine's effects may depend on the sex of the organism. OBJECTIVE: The present study addressed four questions: 1) Will female rats self-administer nicotine? 2) Does self-administration by females vary as a function of estrous cycle? 3) Does self-administration by females differ from that of males? 4) Does self-administration of nicotine result in up-regulation of nicotinic receptor binding and are these changes similar in males and females? METHODS: Male and female Sprague-Dawley rats were allowed to self-administer nicotine at one of four doses (0.02-0.09 mg/kg, free base) on both fixed and progressive ratio schedules of reinforcement. RESULTS: Females acquired nicotine self-administration across the entire range of doses. Acquisition of self-administration at the lowest dose was faster in females than males. However, few sex differences were found in the number of active responses, number of infusions, or total intake of nicotine during stable fixed ratio self-administration. In contrast, females reached higher break points on a progressive ratio. For both schedules, females had shorter latencies to earn their first infusion of each session and demonstrated higher rates of both inactive and timeout responding. There was no effect of estrous cycle on self-administration during either fixed or progressive ratio sessions. Self-administered nicotine resulted in average arterial plasma nicotine levels between 53 and 193 ng/ml and left hemi-brain levels between 174 and 655 ng/g, depending on dose. Nicotine self-administration produced similar up-regulation of nicotinic receptor binding sites in males and females, as reflected by increased right hemi-brain binding of [3H]-epibatidine, when compared to the brains of untreated control rats. CONCLUSIONS: These results suggest that while males and females may regulate their intake of nicotine similarly under limited access conditions, the motivation to obtain nicotine is higher in females.

Nicotine self-administration in rats on a progressive ratio schedule of reinforcement.

RATIONALE: Robust intravenous (i.v.) nicotine self-administration (SA) in rats has been reported by several laboratories, including our own, using fixed ratio (FR) schedules of reinforcement. Studies on other drugs of abuse, however, suggest that progressive ratio (PR) schedules may provide additional information not gained using FR schedules. OBJECTIVE: Here, we attempt to establish and characterize nicotine SA on a PR. METHODS: One study allowed animals to acquire SA on a FR at four doses of nicotine (0.02, 0.03, 0.06, 0. 09 mg/kg) before being switched to a PR. A second study examined extinction by saline substitution or pretreatment with the nicotinic antagonist, mecamylamine, including a preliminary analysis into the role of secondary reinforcers in the extinction process. RESULTS: SA of nicotine on a PR was stable across repeated sessions. The number of infusions earned on a PR correlated with infusion rate on a FR; however, a large portion of the variance in SA on a PR could not be accounted for by infusion rate on a FR. Infusions on a PR increased across the same range of doses that produced a decrease in the infusion rate on a FR. Extinction of responding occurred after saline substitution or pretreatment with mecamylamine, and animals re-acquired when nicotine was again available without pretreatment. The presence of drug-paired stimuli appeared to lengthen the extinction process. CONCLUSIONS: Nicotine supports stable SA on a PR. Since PR and FR schedules may measure different aspects of nicotine reinforcement, PR schedules may be valuable in further characterizing group and individual differences in nicotine reinforcement.

Confocal laser tomographic analysis of the retina in eyes with macular hole formation and other focal macular diseases.

To study the retinal surface in the human eye in normal and diseased states we used laser scanning tomography. The confocal arrangement of the laser tomographic scanner permits examination of retinal topography in the axis perpendicular to the retinal surface. The eyes examined with the laser tomographic scanner included normal eyes, eyes with macular holes, impending macular holes, radiation retinopathy, macular edema, photocoagulation scars, subfoveal scars, and serous detachment of the fovea associated with subretinal neovascularization. The laser tomographic scanner is a new method that allows measurements of the topography of the internal limiting membrane in the macular area and may improve our understanding of the pathophysiologic characteristics and treatment of a variety of disorders of the macula.

Evaluation of descending aortic flow volumes and effective orifice area through aortic coarctation by spatiotemporal integration of color Doppler data: An in vitro study.

Flow volumes in an in vitro model of the aorta with 3 different degrees of stiffness (stiff, moderately stiff, and compliant) proximal to a coarctation were calculated by using a digital color Doppler echocardiography flow calculation method that semiautomatically integrates spatial and temporal color flow velocity data. These flow volumes were compared with those obtained by the conventional pulsed Doppler method with reference to ultrasonic flowmeter. Flow volumes determined by the automated method agreed well with those obtained by ultrasonic flowmeter, even in this compliant aorta model with vessel size changing with pulsation, whereas the pulsed Doppler method overestimated the reference data, especially for more compliant descending aortic segments. The combination of flow data with continuous wave Doppler allows definition of effective orifice area for coarctation.

Accuracy of Doppler methods for estimating peak-to-peak and peak instantaneous gradients across coarctation of the aorta: An In vitro study.

Although data exist that address the attempt to correlate noninvasive Doppler-derived pressure gradients with invasive catheter pressure gradients in patients with coarctation of the aorta, few data exist about stiffness of the proximal descending aorta (precoarctation) and its relation to these pressure measurements. In this study, an in vitro flow model of a simulated neonatal aorta with a coarctation was developed. Three proximal descending aortas of different stiffnesses were used. The stiffness index of the proximal descending aorta was calculated as beta = ln [systolic pressure/diastolic pressure/(systolic diameter - diastolic diameter)]. We evaluated pressure gradients obtained by continuous wave Doppler and standard catheter methods and looked at acceleration of flow velocity determined by pulsed wave Doppler in the 3 precoarctation segments of differing stiffnesses. Pressures in the proximal descending aorta (precoarctation) increased with increasing stiffness, ranging from 105 mm Hg (soft) to greater than 300 mm Hg (stiff). Continuous wave Doppler instantaneous pressure gradients overestimated the catheter instantaneous pressure gradients substantially (mean 41% +/- 19%). The stiffer the precoarctation segment, the more the degree of overestimation: soft, 0% to 63% (= 3.47); medium, 13% to 54% (beta = 4.42); and stiff, 43% to 66% (beta = 5.91). Inclusion of the precoarctation velocity [V1] component in the Bernoulli equation did not significantly improve the correlation or the agreement. An additional observation was that pullback catheter peak-to-peak gradients were higher than simultaneous peak-to-peak gradients. In the stiff aorta, this difference could be greater than 22 mm Hg (>19%). Acceleration of flow velocity toward the coarctation was evident by pulsed wave Doppler interrogation. Increasing the stiffness of the precoarctation segment also increased the degree of acceleration within this proximal segment: soft, 0.4 to 0.8 m/s; medium, 0.5 to 1. 4 m/s; and stiff, 0.7 to 1.5 m/s. These data suggest that increasing stiffness of the proximal descending aorta can alter the continuous wave detected Doppler gradient and although the gradient itself has increased, it may not predict accurately the true severity of the localized, most severely obstructed segment.

Optimizing ventricular shape in anterior restoration.

Ishemic dilated cardiomyopathy results from altered muscle mechanics. Ventricular restoration is aimed at altering the volume and shape changes that follow myocardial infarction. Optimal surgical methods to achieve this goal are not well defined, but it has been shown that sphericity is an important determinant of long-term outcome. We present the rationale and techniques for returning the globular remodeled ventricle to a more elliptical shape. Clinical data from our RESTORE registry does not suggest an improvement in early or late mortality with such methods but opens the way for late evaluation of functional and exercise capacity.

The structure and function of the helical heart and its buttress wrapping. I. The normal macroscopic structure of the heart.

The Gordian knot of anatomy has been the architectural arrangement of ventricular muscle mass, which may have finally become understood. The description of Francisco Torrent-Guasp's model of the helical heart is presented, which includes the cardiac structures that produce 2 simple loops that start at the pulmonary artery and end in the aorta. An unscrolled ventricular band is shown, achieved by blunt dissection that extends between the points of origin of the right ventricle, at the pulmonary artery root, to termination at the aortic root, in the left ventricle. These components include a spiral horizontal basal loop that surrounds the right and left ventricular cavities, and changes direction to cause a second spiral, produced by almost vertically oriented fibers, giving rise to the helical configuration of the ventricular myocardial band. These anatomic structures are successively activated, as with a peristaltic wave, starting at the right ventricle (just below the pulmonary artery) and progressing toward the aorta to produce a sequence of narrowing, caused by the basal loop contraction, shortening (related predominantly to the descendant segment contraction), lengthening (produced by the ascendant segment contraction), and widening, as a consequence of several factors that act during ventricular myocardium relaxation. These sequences control the ventricular events responsible for ejection to empty and suction to fill. These mechanical interactions of structure and function are defined in relation to chronologic location of the successive cardiac functional events in the aortic, left ventricular, and left atrial recordings.

The structure and function of the helical heart and its buttress wrapping. III. The electric spiral of the heart: The hypothesis of the anisotropic conducting matrix.

The study of the dissemination of the electric impulse throughout the ventricular myocardium, which gave rise to the current theories, was performed without taking into consideration the complex architecture of the cardiac muscle elucidated by more recent researchers. We propose a novel hypothesis based on the special macroscopic structure of the heart, the anisotropic electric and mechanical behavior of the myocardium, the characteristics of the intercellular matrix and its very special collagen scaffolding, chemical composition, and biochemistry. The unique properties of the intercellular matrix would make it especially suited to function, in conjunction with the specialized conducting system (His-Purkinje system), as an efficient anisotropic conductor for the spread of electric activation in the heart, and to allow an optimal sequence of excitation-contraction coupling that results in the coordination of effective myocardial contraction in birds and mammals of the most varied known heart rates.