Abstract
OBJECTIVES
This study aims to characterize the material properties of ascending thoracic aortic aneurysmal tissue, using regional biomechanical assessment of both tensile and dissection ...propagation peel strength.
METHODS
Thirty-four aneurysm specimens (proximal thoracic aorta) were harvested en-bloc from patients undergoing surgery for aneurysm replacement. Specimens were processed into regional samples of similar shapes covering the whole aneurysm isosurface, according to a structured protocol, in both orientations (longitudinal and circumferential). Thickness mapping, uniaxial tensile and peel tests were conducted, enabling calculation of the following parameters: true stress/strain, tangential modulus, tensile strength, peeling force and dissection energy. Two constitutive material models were used (hyperelastic models of Delfino and Ogden) to fit the data. A circumferential strip of tissue was also obtained for computational histology regional quantification of (i) elastin, (ii) collagen and (iii) smooth muscle cells.
RESULTS
The aortic wall was thinner on the outer curve (2.21, standard deviation (SD) 0.4 mm vs inner curve 2.50, SD 0.12 mm). Advanced patient age and higher pulse wave velocity (externally measured) were predictors of increased aortic wall thickness. Tensile strength was higher in the circumferential versus longitudinal direction when analysed according to anatomical regions. Both peel force (35.5, 22 N/m) and dissection energy (88.5, 69 J/m2) were on average lowest at the outer curve of the aneurysm in the longitudinal orientation. Delfino and Ogden model constants varied throughout anatomical regions, with the outer curve being associated a higher ɑ constant (Delfino) and lower µ1 constant (Ogden) (P < 0.05) indicating increased stiffness. Histologically, collagen abundance was significantly related to circumferential and longitudinal strength (P= 0.010), whilst smooth muscle cell count had no relation with any mechanical property (P > 0.05).
CONCLUSIONS
Our results suggest that the outer aortic curve is more prone to dissection propagation and perhaps less prone to rupture than the inner aortic curve. This strengthens the notion of disease heterogeneity in ascending thoracic aortic aneurysms and has implications for the pathogenesis of aortic dissection.
The unmet clinical need in the management of ascending thoracic aortic aneurysms (ATAA) is the lack of an accurate predictive model or biomarker for the risk of acute aortic syndrome 1, 2, Current guidelines rely only on aneurysm size and growth to determine the risk of type A aortic dissection (TAAD) 3.
Swelling of lymph nodes (LNs) is commonly observed during the adaptive immune response, yet the impact on T cell (TC) trafficking and subsequent immune response is not well known. To better ...understand the effect of macro-scale alterations, we developed an agent-based model of the LN paracortex, describing the TC proliferative response to antigen-presenting dendritic cells alongside inflammation-driven and swelling-induced changes in TC recruitment and egress, while also incorporating regulation of the expression of egress-modulating TC receptor sphingosine-1-phosphate receptor-1. Analysis of the effector TC response under varying swelling conditions showed that swelling consistently aided TC activation. However, subsequent effector CD8
TC production was reduced in scenarios where swelling occurred too early in the TC proliferative phase or when TC cognate frequency was low due to increased opportunity for TC exit. Temporarily extending retention of newly differentiated effector TCs, mediated by sphingosine-1-phosphate receptor-1 expression, mitigated any negative effects of swelling by allowing facilitation of activation to outweigh increased access to exit areas. These results suggest that targeting temporary effector TC retention and egress associated with swelling offers new ways to modulate effector TC responses in, for example, immuno-suppressed patients and to optimize of vaccine design.
Body mass index and risk of ovarian cancer Leitzmann, Michael F.; Koebnick, Corinna; Danforth, Kim N. ...
Cancer,
15 February 2009, Letnik:
115, Številka:
4
Journal Article
Recenzirano
Odprti dostop
BACKGROUND:
Convincing epidemiologic evidence links excess body mass to increased risks of endometrial and postmenopausal breast cancers, but the relation between body mass index (BMI) and ovarian ...cancer risk remains inconclusive. Potential similarities regarding a hormonal mechanism in the etiology of female cancers highlight the importance of investigating associations according to menopausal hormone therapy (MHT) use. However, to the authors' knowledge, data addressing whether the relation between BMI and ovarian cancer differs by MHT use are very sparse.
METHODS:
The authors prospectively investigated the association between BMI and ovarian cancer among 94,525 US women who were followed between 1996 through 1997 to December 31, 2003. During 7 years of follow‐up, 303 epithelial ovarian cancer cases were documented.
RESULTS:
Compared with normal weight women (BMI of 18.5‐24.9 kg/m2), the multivariate relative risk (MVRR) of ovarian cancer for obese women (BMI of ≥30 kg/m2) in the cohort as a whole was 1.26 (95% confidence interval 95% CI, 0.94‐1.68). Among women who never used MHT, the MVRR for obese versus normal weight women was 1.83 (95% CI, 1.18‐2.84). In contrast, no relation between BMI and ovarian cancer was apparent among women who ever used MHT (MVRR = 0.96; 95% CI, 0.65‐1.43; P interaction = 0.02). Exploratory analyses also suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer (MVRR comparing obese vs normal weight women = 1.36; 95% CI, 1.00‐1.86), but no relation with BMI was apparent among women with a positive family history of ovarian cancer (MVRR = 0.74; 95% CI, 0.34‐1.62 P interaction = .02).
CONCLUSIONS:
Based on the results of the current study, the authors suspect that obesity is associated with enhanced ovarian cancer risk through a hormonal mechanism. Cancer 2009. Published 2009 by the American Cancer Society.
The authors prospectively investigated the association between body mass index (BMI) and ovarian cancer among US women from 1996 through 1997 to December 31, 2003. Exploratory analyses suggested a positive association between BMI and ovarian cancer among women without a family history of ovarian cancer, but no relation with BMI was apparent among women with a positive family history of ovarian cancer. Obesity was suspected as being associated with enhanced ovarian cancer risk through a hormonal mechanism.
Objective
To assess lymphatic flow adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ.
...Methods
Twelve rats were infused with saline (intravenous infusion, 0.2 mL/min/100 g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as lymphocyte velocity and density before, during, and after infusion.
Results
A 10‐fold increase in lymphocyte velocity (0.1–1 mm/s) and a sixfold increase in flow rate (0.1–0.6 μL/min), were observed post infusion, respectively. There were also increases in contraction frequency and fractional pump flow one minute post infusion. Time‐averaged wall shear stress increased 10 fold post infusion to nearly 1.5 dynes/cm2. Similarly, maximum shear stress rose from 5 to 40 dynes/cm2.
Conclusions
Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, the increases in lymphatic contraction frequency, lymphocyte velocity, and shear stress were significant. Lymph pumping increased post infusion, though changes in lymphatic diameter were not statistically significant. These results indicate that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymphocyte velocity, and flow. These changes, consequently, resulted in large increases in wall shear stress, which could then activate NO pathways and modulate lymphatic transport function.
Aims
We sought to determine if heart failure (HF) care with a goal to lower N‐terminal pro B‐type natriuretic peptide (NT‐proBNP) concentrations, compared with standard of care (SOC) management, is ...associated with improvement in echocardiographic parameters of cardiac structure and function.
Methods and results
Of 151 subjects with HF due to left ventricular systolic dysfunction (LVSD) prospectively randomized to NT‐proBNP‐guided vs. SOC HF care, 116 had serial echocardiographic data. Endpoints in this echocardiographic study included the relationship between change in NT‐proBNP and LV reverse remodelling, as well as associations between biomarker‐guided therapy and measures of diastolic function, right ventricular (RV) size and function, estimates of LV filling pressure and RV systolic pressure (RVSP), and the degree of mitral regurgitation (MR). After a mean of 10 months of study procedures, in adjusted analyses, final NT‐proBNP concentrations predicted risk of remodelling hazard ratio (HR) ↑LV end‐diastolic volume index = 1.43, 95% confidence interval (CI) 1.10–1.86, P = 0.007; HR ↑LV end‐systolic volume index = 1.54, 95% CI 1.10–1.91, P = 0.01; HR ↓LV ejection fraction (LVEF) = 1.53, 905% CI 1.12–1.89, P = 0.02. In addition to greater improvement in LVEF and reductions in LV volume, compared with SOC, NT‐proBNP‐guided patients showed significant decreases in the ratio of early transmitral peak velocity to early diastolic peak annular velocity (E/E'), pulmonary vein peak S velocity, RV fractional area change, RVSP, and MR severity.
Conclusion
NT‐proBNP concentrations may serve as a non‐invasive indicator of the state of cardiac structure and function in HF due to LVSD. Multiple, prognostically meaningful echocardiographic variables improved more significantly in patients treated with NT‐proBNP‐guided care vs. SOC.
Trial registration: NCT00351390.
Implementing a self-refereeing system presents a unique challenge in sports education, particularly in academic and training settings where officiated sports prevail. However, Ultimate Frisbee stands ...out by entrusting players with both athlete and referee roles, introducing distinctive ethical complexities. This manuscript is intended to evaluate ethical behavior and self-control within the Spirit of the Game (SOTG) scoring system in Elite Ultimate. To address these, Ultimate employs the (SOTG) scoring system, integral since the sport's inception in the late 1980s. SOTG aims to enhance and evaluate athletes' ethical conduct. This study evaluates SOTG's effectiveness in elite-level Ultimate, analyzing variations across divisions and age groups in three high-level tournaments.
Using a cross-sectional design, data were collected from five international Ultimate tournaments in 2022. Teams spanned diverse age groups (under 17 to over 50) and divisions (women's, mixed, open). Post-match, teams assessed opponents' SOTG in five domains: Rules knowledge, fouls, fairness, attitude/self-control, and communication. Ratings used a 5-point Likert scale ("poor" to "excellent"). An overall SOTG score was calculated by aggregating domain scores.
Our study consistently revealed high SOTG scores, reflecting strong sportsmanship. "Positive attitude and self-control" consistently ranked highest, while "Knowledge and use of the rules" scored lowest. Divisional differences in SOTG were statistically insignificant. Notably, WMUCC2022 (participants aged 30+) had significantly higher SOTG scores, possibly indicating age-related self-control improvement or evolving sport culture. Lower rules knowledge scores may stem from linguistic translation challenges.
Self-refereeing promotes ethical behavior across divisions and age groups. SOTG underscores sportsmanship's importance and aligns with International Olympic Committee (IOC) and with Sustainable Development Goals (SDGs), particularly SDG 3, 4, 5 and 16 fostering a fairer, healthier, and more peaceful world.
Lymphatic System Flows Moore, James E; Bertram, Christopher D
Annual review of fluid mechanics,
01/2018, Letnik:
50, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The supply of oxygen and nutrients to tissues is performed by the blood system and involves a net leakage of fluid outward at the capillary level. One of the principal functions of the lymphatic ...system is to gather this fluid and return it to the blood system to maintain overall fluid balance. Fluid in the interstitial spaces is often at subatmospheric pressure, and the return points into the venous system are at pressures of approximately 20 cmH
2
O. This adverse pressure difference is overcome by the active pumping of collecting lymphatic vessels, which feature closely spaced one-way valves and contractile muscle cells in their walls. Passive vessel squeezing causes further pumping. The dynamics of lymphatic pumping have been investigated experimentally and mathematically, revealing complex behaviors that indicate that the system performance is robust against minor perturbations in pressure and flow. More serious disruptions can lead to incurable swelling of tissues called lymphedema.
Effectiveness of School-Based Influenza Vaccination King, James C; Stoddard, Jeffrey J; Gaglani, Manjusha J ...
New England journal of medicine/The New England journal of medicine,
12/2006, Letnik:
355, Številka:
24
Journal Article
Recenzirano
Odprti dostop
Children are important vectors of the influenza virus. In this study, investigators vaccinated children in several intervention schools and compared the occurrence of influenza-like illness in their ...households with that in households of children in control schools. Intervention-school households had significantly fewer outcomes related to influenza-like illness than did control-school households, including household members with any influenza-like symptoms, fever plus cough or sore throat, medical visits for children, absenteeism among elementary and high school students, and workdays lost by adults during the recall week.
Investigators vaccinated children in several intervention schools and compared the occurrence of influenza-like illness with that in control schools. Intervention-school households had significantly fewer outcomes related to influenza-like illness than did control-school households.
Children are important vectors for the spread of influenza within households and communities.
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6
Focusing efforts for influenza vaccination on healthy children may therefore be an effective and practical method of reducing the burden of influenza in the community.
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10
A recent pilot study demonstrated the feasibility of using trivalent, live attenuated influenza vaccine (FluMist, MedImmune) to vaccinate children in school and suggested there was a significant reduction in the rate of influenza-related outcomes in the households of children enrolled in the study.
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The primary objective of our study was to assess the effect of a school-based vaccination program on . . .
There has existed a severe ventilator deficit in much of the world for many years, due in part to the high cost and complexity of traditional ICU ventilators. This was highlighted and exacerbated by ...the emergence of the COVID-19 pandemic, during which the increase in ventilator production rapidly overran the global supply chains for components. In response, we propose a new approach to ventilator design that meets the performance requirements for COVID-19 patients, while using components that minimise interference with the existing ventilator supply chains. The majority of current ventilator designs use proportional valves and flow sensors, which remain in short supply over a year into the pandemic. In the proposed design, the core components are on-off valves. Unlike proportional valves, on-off valves are widely available, but accurate control of ventilation using on-off valves is not straightforward. Our proposed solution combines four on-off valves, a two-litre reservoir, an oxygen sensor and two pressure sensors. Benchtop testing of a prototype was performed with a commercially available flow analyser and test lungs. We investigated the accuracy and precision of the prototype using both compressed gas supplies and a portable oxygen concentrator, and demonstrated the long-term durability over 15 days. The precision and accuracy of ventilation parameters were within the ranges specified in international guidelines in all tests. A numerical model of the system was developed and validated against experimental data. The model was used to determine usable ranges of valve flow coefficients to increase supply chain flexibility. This new design provides the performance necessary for the majority of patients that require ventilation. Applications include COVID-19 as well as pneumonia, influenza, and tuberculosis, which remain major causes of mortality in low and middle income countries. The robustness, energy efficiency, ease of maintenance, price and availability of on-off valves are all advantageous over proportional valves. As a result, the proposed ventilator design will cost significantly less to manufacture and maintain than current market designs and has the potential to increase global ventilator availability.
Four commercially available stent designs (two balloon expandable-Bx Velocity and NIR, and two self-expanding-Wallstent and Aurora) were modeled to compare the near-wall flow characteristics of ...stented arteries using computational fluid dynamics simulations under pulsatile flow conditions. A flat rectangular stented vessel model was constructed and simulations were carried out using rigid walls and sinusoidal velocity input (nominal wall shear stress of 10+/-5 dyn/cm2). Mesh independence was determined from convergence (<10%) of the axial wall shear stress (WSS) along the length of the stented model. The flow disturbance was characterized and quantified by the distributions of axial and transverse WSS, WSS gradients, and flow separation parameters. Normalized time-averaged effective WSS during the flow cycle was the smallest for the Wallstent (2.9 dyn/cm2) compared with the others (5.8 dyn/cm2 for the Bx Velocity stent, 5.0 dyn/cm2 for the Aurora stent, and 5.3 dyn/cm2 for the NIR stent). Regions of low mean WSS (<5 dyn/cm2) and elevated WSS gradients (>20 dyn/cm3) were also the largest for the Wallstent compared with the others. WSS gradients were the largest near the struts and remained distinctly nonzero for most of the region between the struts for all stent designs. Fully recirculating regions (as determined by separation parameter) were the largest for the Bx Velocity stent compared with the others. The most hemodynamically favorable stents from our computational analysis were the Bx Velocity and NIR stents, which were slotted-tube balloon-expandable designs. Since clinical data indicate lower restenosis rates for the Bx Velocity and NIR stents compared with the Wallstent, our data suggest that near-wall hemodynamics may predict some aspects of in vivo performance. Further consideration of biomechanics, including solid mechanics, in stent design is warranted.
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