Relative Volume Change Research Articles

Effects of thermal treatment on acoustic waves in Carrara marble

Many physical processes in the field of rock physics are influenced by the presence of fractures and microcracks. Therefore, intact rock samples are often used for reproducible experimental studies, and cracks are artificially created by various methods. For this, one possibility is the use of thermal treatments. In this work, twelve different thermal treatments are experimentally studied for dry Bianco Carrara marble under ambient conditions. The focus is primarily on the influence of the cooling rate (slow versus fast cooling) in combination with different applied maximum temperatures. This also raises the question of the influence of the specimen size, which has never been systematically investigated in this context before. Therefore, three sizes of cylindrical core samples are investigated to identify a potential specimen size effect. As effective quantities on the core-scale, the bulk volume, the bulk density, and the P- and S-wave velocities, including shear wave splitting, are examined. To obtain a three-dimensional insight into the mechanisms occurring on the micro-scale level, micro X-ray Computed Tomography (μXRCT) imaging is employed. For both cooling conditions, with increasing maximum temperature, the bulk volume increases, the propagation velocities significantly drop, and shear wave splitting increases. This behavior is amplified for fast cooling. The bulk volume increase is related to the initiated crack volume as μXRCT shows. Based on comprehensive measurements, a logarithmic relationship between the relative bulk volume change and the relative change of the ultrasound velocities can be observed. Although there is a size effect for fast cooling, the relationship found is independent of the specimen size. Also the cooling protocol has almost no influence. A model is derived which predicts the relative change of the ultrasound velocities depending on the initiated relative bulk volume change.

Intravoxel Incoherent Motion MRI and PET in Locally Advanced Cervical Carcinoma Undergoing Concurrent Chemoradiation Therapy

<h3>Purpose/Objective(s)</h3> Dynamic contrast enhanced (DCE) CT or MRI and FDG PET have been used to evaluate the impact of tumor perfusion and metabolism on the course and effectiveness of concurrent chemoradiation therapy (CCRT) for cervical cancer. Combining perfusion and metabolic measures allows better identification of radioresistant sub-volumes: however, use of contrast and additional dose are barriers to frequent dual perfusion-metabolic imaging. Here, we investigated a contrast-free, non-ionizing alternative to DCE: intravoxel incoherent motion (IVIM) MRI which provides both perfusion and diffusion measurements. Our objective was to evaluate changes of PET and IVIM parameters in cervical cancer patients before and during CCRT and to correlate these parameters and their changes with tumor volume response during CCRT. <h3>Materials/Methods</h3> Pre- and on-treatment IVIM scans were performed on 15 cervical cancer patients undergoing definitive chemoradiation (median [range] age: 66 [29 to 85]; FIGO: 1 IB1, 1 IIA, 3 IIB, 1 IIIB, 1 IIIC, 5 IIIC1, 2 IIIC2, 1 IVA; hist: 11 squamous cell carcinoma, 3 endocervical adenocarcinoma, 1 large cell neuroendocrine carcinoma), of whom 14 also underwent pre-treatment PET scans. The on-treatment MRI occurred generally during the last week or shortly after completing EBRT. Diffusion weighted images (DWIs) were acquired at 3T scanners using a free-breathing single shot spin echo planar imaging (EPI) sequence. IVIM MRI maps were generated by Bayesian fitting of a two-compartment IVIM model to the DWIs. Three-dimensional co-registered maps of PET standardized uptake value (SUV) and IVIM diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) were generated. Summary statistics (mean +/- standard deviation) for these and other imaging parameters were calculated pre- and on-treatment. Univariate analysis was performed to determine relationships between relative change in gross tumor volume (ΔGTV) and pre-treatment imaging measurements. <h3>Results</h3> In tumors, pre- versus on-treatment values significantly changed for the following parameters: ΔGTV (66.8 +/- 43.2 vs. 32.0+/-23.0 ml, p<.001) and D (0.00109 +/- 0.00023 vs. 0.00120 +/- 0.00026 mm²/s, p=.02). The perfusion fraction f increased and D* decreased, but not significantly (f: 0.127 +/- 0.022 vs. 0.154 +/- 0.057 %, p=.07, D*: 0.0137 +/- 0.0035 vs. 0.0133 +/- 0.0039 mm²/s, p=.6). Pre-treatment SUV_max (r=.76, p=.002) and SUV_mean (r=.70, p=.007) were positively related with ΔGTV, while pre-treatment f, D*, and D were negatively but not significantly related with ΔGTV (r=-.44, p=.1; D*: r=-.14, p=.6; D: r=-.12, p=.7). <h3>Conclusion</h3> Both perfusion fraction and diffusion coefficient IVIM increased in locally advanced cervical carcinoma patients undergoing CCRT – reflecting changes in the tumor microenvironment during treatment. These weak relationships observed here suggest a potential complementary role and motivating the combined use of these modalities for tumor characterization.

Changes in the renal artery and renal volume and predictors of renal atrophy in patients with complicated type B aortic dissection after thoracic endovascular aortic repair

For complicated Stanford type B aortic dissection (TBAD), thoracic endovascular aortic repair (TEVAR) is the recommended treatment; however, the type of renal artery that should be repaired remains controversial. The study aimed to investigate the changes in the renal artery and renal volume in complicated TBAD after TEVAR and the predictors of renal atrophy. The cohort study retrospectively enrolled patients with acute and subacute complicated TBAD who underwent aortic computed tomography angiography (CTA) 1 month before as well as 1 week and half a year after TEVAR from January 2010 to May 2017. According to the source of blood supply shown in preoperative CT, the renal artery was classified in 3 ways: type 1, supplied by the aortic true lumen; type 2, supplied by the aortic false lumen; or type 3, supplied by both the true and false lumen. A total of 91 patients (81 men and 10 women) with an average age of 48.12±10.35 years were enrolled. Renal arteries were classified as type 1 (n=91), type 2 (n=35), and type 3 (n=56). There was no difference in the distribution of the 3 types on the left and right sides (type 1 vs. type 2 vs. type 3: 52:39 vs. 15:20 vs. 24:32; P=0.152). After TEVAR, type 3 was more likely to have spontaneous healing than type 2 (16.1% vs. 2.9%; P=0.049). There was no significant difference in the preoperative volume of kidneys of the 3 types (type 1 vs. type 2 vs. type 3: 198.23±38.68 vs. 197.37±41.77 vs. 195.10±36.11 mL; P=0.893). The postoperative volume of types 2 and 3 was smaller than that of type 1 (type 1 vs. type 2 vs. type 3: 190.09±43.25 vs. 165.15±52.63 vs. 170.70±45.28 mL; P=0.006). The renal volume was reduced in all 3 types of renal artery, especially in type 2 (the change of renal volume for type 1 vs. type 2 vs. type 3: -8.14±29.31 vs. -32.22±41.59 vs. -24.41±38.44 mL; P=0.001). The relative change of renal volume for type 1 vs. type 2 vs. type 3: (-3.64±15.69)% vs. (-16.00±21.29)% vs. (-11.97±18.22)%; P=0.001). During the median follow-up of 668 days, 7 patients (7.7%) belonging to types 2 and 3 developed renal atrophy. False lumen thrombosis in the abdominal aorta and/or the renal artery was the predictor of renal atrophy [hazard ratio (HR) =17.757; P=0.008]. Patients with type 2 or 3 renal artery and false lumen thrombosis in the abdominal aorta and/or renal artery should be monitored closely and actively intervened to prevent renal atrophy.

Interfractional Dynamics of Glioblastoma Treated on MRI-Linac

<h3>Purpose/Objective(s)</h3> Few studies have investigated glioblastoma (GBM) changes during chemoradiotherapy (chemoRT). Many lesions grow and many post-operative resection cavities (RC) shrink when comparing pre- and post-treatment MRI. MRI-Linac offers the opportunity to investigate tumor dynamics during chemoRT without standalone MRI. The purpose of this study was to investigate intracranial changes during chemoRT using imaging from MRI-Linac for future prospective trials. <h3>Materials/Methods</h3> Using an IRB-approved prospective cohort of 34 GBM patients undergoing 30 fractions of chemoRT to 60 Gy on a 0.35T MRI-Linac, tumor/edema (lesion) and RC dynamics throughout treatment were analyzed on T2-weighted treatment set-up scans. RC/lesion change was measured for weekly time points (W1-W6). Absolute and relative volume (>1 indicates growth, <1 indicates shrinkage) changes compared to the planning scan (PL) and migration distance, the largest linear distance that RC/lesion migrated from PL, were calculated. Target margins required through treatment to avoid lesion growth out of margins and how much normal brain can be saved by adapting to shrinking RC were investigated. <h3>Results</h3> 8 patients had RC only, 10 had lesion only, and 16 had both RC and lesion. The volumes and migration distances (median (range)) for RCs and lesions, are shown (table). The treatment margin required to avoid the average lesion from growing out of margins at any point during chemoRT from PL (i.e., migration distance) is 1.30 cm (max 4.1 cm). Adapting to a shrinking RC (RC only or RC with small lesion <20 ml (n=11)), assuming a 2 cm CTV adapted at W5, saves 26.92 ml (9.66 – 58.63 ml) of normal appearing brain from full RT dose. <h3>Conclusion</h3> Clinically significant anatomic changes were seen in GBM patients during chemoRT. Patients with unresected lesions require large RT margins or volume expansions for growth during RT. As RCs shrink, margins can be reduced to save normal brain. Limited volume GBM boost trials should strongly consider adaptive RT given the significant interfractional variability.

Doxycycline for the treatment of breast cancer-related lymphedema.

Purpose: Secondary lymphedema is a common complication of cancer treatment for which no effective drug treatments yet exist. Level I clinical data suggests that doxycycline is effective for treating filariasis-induced lymphedema, in which it decreases tissue edema and skin abnormalities; however, this treatment has not been tested for cancer-related lymphedema. Over the past year, we used doxycycline in an off-label manner in patients with breast cancer-related secondary lymphedema. The purpose of this report was to retrospectively analyze the efficacy of this treatment. Methods: Patients who presented to our lymphedema clinic between January 2021 and January 2022 were evaluated, and barring allergies or contraindications to doxycycline treatment, were counseled on the off-label use of this treatment. Patients who wished to proceed were treated with doxycycline (200mg given orally once daily) for 6weeks. After IRB approval of this study, lymphedema outcomes were retrospectively reviewed. Results: Seventeen patients with a mean follow-up of 17.0 ± 13.2weeks were identified in our retrospective review. Although doxycycline treatment had no significant effect on relative limb volume change or L-Dex scores, we found a significant improvement in patient-reported quality of life. Analysis of patient responses to the Lymphedema Life Impact Scale showed a significant improvement in the total impairment score due to improvements in the physical and psychological well-being subscales (p = 0.03, p = 0.03, p = 0.04, respectively). Conclusion: This small, retrospective study did not show significant improvements in limb volume or L-Dex scores in patients with breast cancer-related lymphedema treated with doxycycline. However, our patients reported improvements in quality-of-life measures using a validated lymphedema patient-reported outcome instrument. Our results suggest that doxycycline may be of use in patients with breast cancer-related lymphedema; however, larger and more rigorous studies are needed.

Interannual and Monthly Variability of Typical Inland Lakes on the Tibetan Plateau Located in Three Different Climatic Zones

Changes in lake water volume can reflect variations in regional hydrometeorology and are a sensitive indicator of regional environmental change. The Tibetan Plateau, referred to as the “Asian Water Tower”, has a large number of lakes. These lakes are in a natural state and are relatively unaffected by human activities. Understanding the changes to lake water volume is a key issue for the study of lake-atmosphere interactions and the effects of lake expansion and contraction on regional climate. By using multisource remote sensing and water level observations, this study systematically analyzed inter-annual changes from 1970 to 2021 of three typical inland lakes basin (Bamu Co-Peng Co basin, Langa Co-Mapum Yumco basin andLongmu Co-Songmuxi Co basin), which are located in different climatic regions of the Tibetan Plateau and monthly changes from 2019 to 2021 of Bamu Co, Langa Co and Longmu Co in the lake area, water level, and water volume. In addition, the study analyzed the response of lakes in different climate regions to climate change from 1979 to 2018. The main conclusions are as follows. (1) From 1970 to 2021, there were similar trends in lake changes between the primary and twin lakes. (2) The changes to lakes in different climatic regions are different: lakes in the monsoon-dominated region showed a significant trend of expansion from 2000 to 2014, but the trend slowed down and stabilized after 2014; lakes in the westerlies-dominated region showed a small expansion trend; lakes in the region affected by both westerlies and the monsoon showed an overall shrinking trend. (3) The monthly variation of lake water volume showed a trend of first increasing and then decreasing, with the largest relative change of lake water volume in August and September. (4) Precipitation is a dominant factor controlling lake variation during the year. (5) Temperature and precipitation are dominant meteorological elements affecting the decadal variation of the lake, and with the warming of the TP, temperature plays an increasingly important role.

Accurate measures of changes in regional lung air volumes from chest x-rays of small animals

Objective. To develop a robust technique for calculating regional volume changes within the lung from x-ray radiograph sequences captured during ventilation, without the use of computed tomography (CT). Approach. This technique is based on the change in transmitted x-ray intensity that occurs for each lung region as air displaces the attenuating lung tissue. Main results. Lung air volumes calculated from x-ray intensity changes showed a strong correlation (R 2 = 0.98) against the true volumes, measured from high-resolution CT. This correlation enables us to accurately convert projected intensity data into relative changes in lung air volume. We have applied this technique to measure changes in regional lung volumes from x-ray image sequences of mechanically ventilated, recently-deceased newborn rabbits, without the use of CT. Significance. This method is suitable for biomedical research studies,enabling quantitative regional measurement of relative lung air volumes at high temporal resolution, and shows great potential for future clinical application.

Cardiac resynchronization therapy: association between genetically determinated dilated cardiomyopathy and dissinchronopathy

Abstract Background Patients with non-ischemic dilated cardiomyopathy (DCM) and left bundle branch block (LBBB) often undergoes cardiac resynchronization therapy (CRT). Despite CRT only a small group of patients restore normal left ventricular geometry and function. Many predictors of response to CRT have been described, but there are still insufficient data on the role of genetic mutations in sarcomere, cytoskeletal or desmosomal genes. Purpose To asses the role of genetic background as predictor of response after CRT in patient DCM and LBBB. Methods We retrospectively analyzed DCM patients with successful CRT implantation and available genetic testing consecutively included in the CRT-Registry of our Institution. DCM was defined by the presence of left ventricular or biventricular dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease sufficient to cause global systolic impairment. Changes in main echocardiographic parameters: left ventricular ejection fraction (LVEF), LV End Systolic and End Diastolic Volume (LVESV and LVEDV), where compared between basal and 24–48 months of follow up. LV remodeling was defined by relative changes (Δ) in LV End Systolic Volume (LVESV) [(follow-up LVESV − PRE LVESV) / PRE LVESV × 100)]. Patients were considered super-responders (SR) if LVEF at 24–48 months was&amp;gt;50%. Genetic testing was done by Next Generation DNA and all variants were validated with bidirectional Sanger sequencing. Variants of uncertain significance (VUS) were excluded from the analysis. Patients being carrier of pathogenic (P) or likely pathogenic (LP) variants were considered affected by genetic DCM (GEN+ DCM). Patients non carrier of P/LP variants and with no evidence of familial disease were considered affected by non-genetically determined DCM (GEN− DCM). Results 73 patients met the inclusion criteria, 23 patients were GEN+ DCM, the remaining 50 patients had negative genetic test and no family history of DCM. Baseline characteristics were similar between groups. GEN− group was characterized by a greater improvement in LVEF (39±12 vs 29±12, p=0,006) and a greater relative reduction in LVESV (ΔLVESV 43% vs 18%, p=0,007). GEN− patients had a 33 ml higher mean LVESV reduction at 24–48 months after CRT, indipendently of their respective baseline values. 20 patients (27% of the total population) suffered of heart failure related death, heart transplantation or left ventricular assistance device implantation during follow up and the prevalence was significantly higher in GEN+ group (43% vs 20%, p=0,037). Coherently, patients in the GEN+ group showed a lower prevalence of super responders (4%, vs 24%, p=0,02) after CRT. Conclusions Non-genetically determined DCM DCM is associated with a better clinical and instrumental response to CRT and a higher probability of being super responders. Furthermore, our data support the hypothesis about dyssyncronopathy as a specific clinical entity inside DCM diseases. Funding Acknowledgement Type of funding sources: None.

Global online interest in finasteride sexual side effects.

Prior literature has suggested that finasteride may negatively impact men's sexual health. In 2011, the Food and Drug Administration(FDA) provided a warning on finasteride drug labels to incorporate sexual side effects such as reduced libido and erectile dysfunction. We aimed to evaluate global online interest in finasteride sexual side effects, their penetrance and variation, and how they compared overtime. We also aimed to evaluate the influence of the FDA label warnings on web-based searches for finasteride side effects. We utilized Google search engine from January 2004 to December 2020 to include separate trends from web searches of "Propecia," "Propecia side effects," "finasteride", "finasteride side effects", and "post-finasteride syndrome" compared amongst the United States, United Kingdom, and Australia. We performed join-point regression analysis. We compared the annual relative search volume (ARSV) and annual percentage change (APC) to evaluate for loss or gain of interest in the respective key terms. We determined thatthe average ARSV for "finasteride" was 14.8% in 2004 and increased significantly to 57.3% in 2020 (APC: +9.25%, 95% CI 8 to 10.5, p < 0.001). Likewise, there was significant increased interest in "finasteride side effects" (APC: +20.7, p < 0.001) and "post-finasteride syndrome" (APC: +29.2; p < 0.001) in the United States overtime. Finally, when we compared trends before and after the FDA warnings, the average ASRV of "finasteride", "finasteride side effects", and "post-finasteride syndrome" all increased significantly (p = 0.001, p = 0.014, p < 0.001), respectively. Thus, it is evident that there is a global web-based interest in finasteride and its sexual health side effects, particularly after the FDA warning in 2011. There is boosted public awareness, and thus providers should have more detailed and careful conversations with patients prior to starting a 5α-reductase inhibitor such as finasteride.

Multispectral raster-scanning optoacoustic mesoscopy differentiate lesional from non-lesional atopic dermatitis skin using structural and functional imaging markers

Atopic dermatitis (AD) is a chronic and pruritic skin inflammatory disease causing a significant burden to health care management and patient’s quality of life. Seemingly healthy skin or non-lesional sites on AD patients still presents skin barrier defects and immune response, which can develop to AD at a later stage. To investigate further the balance between the epidermal barrier impairment and intrinsic immune dysregulation in AD, we exploited multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) to image lesional and non-lesional skin areas on AD patients of different severities non-invasively to elucidate their structural features and functional information. Herein, we demonstrate the objective assessment of AD severity using relative changes in oxygen saturation (δsO2) levels in microvasculature along with other structural parameters such as relative changes in epidermis thickness (δET) and total blood volume (δTBV) between the lesional and non-lesional areas of the skin. We could observe an increasing trend for δsO2 and δTBV, which correlated well with the subjective clinical Scoring Atopic Dermatitis (SCORAD) for evaluating the severity. Notably, δET showed a decreasing trend with AD severity, indicating that the difference in epidermal thickness between lesional and non-lesional area of the skin decreases with AD severity. Our results also correlated well with conventional metrics such as trans-epidermal water loss (TEWL) and erythrosine sedimentation rate (ESR). We quantified the δsO2 and δET changes to objectively evaluate the treatment response before and four months after treatment using topical steroids and cyclosporine in one severe AD patient. We observed reduced δsO2 and δET post treatment. We envision that in future, functional and structural imaging metrics derived from ms-RSOM can be translated as objective markers to assess and stratify the severity of AD and understand the function of skin barrier dysfunctions and immune dysregulation. It could also be employed to monitor the treatment response of AD in regular clinical settings.

Quantitative Evaluation of Chronic Obstructive Pulmonary Disease and Risk Prediction of Acute Exacerbation by High-Resolution Computed Tomography.

Objective It is imperative to popularize the tertiary prevention of chronic obstructive pulmonary disease (COPD) and to improve the diagnosis and treatment. Methods COPD patients were divided into mild (n = 18), moderate (n = 20), severe (n = 24), and extremely severe (n = 22) groups for performing high-resolution computed tomography (HRCT) and pulmonary function test. Serum procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) were detected, and the occurrence rate of acute exacerbation COPD (AECOPD) was recorded during a 12-months follow-up period. Results With an increase in the severity grade, the HRCT indexes, including emphysema index (EI), 1st and 15th percentile of inspiratory attenuation distribution (Perc1 and Perc15), ratio of expiratory/inspiratory mean lung density (MLDex/in) and lung volume (LVex/in), and ratio of the wall thickness to the outer diameter of the lumen (TDR), as well as percentage of the wall area to the total cross-sectional area (WA%) were increased with a decreased change in relative lung volume with attenuation values between −860 and −950 HU (RVC−860to −950) and lumen area (Ai). These were correlated with the ratio of forced expiratory volume in 1 sec (FEV1) over forced vital capacity (FVC) (FEV1/FVC), the percentage of FEV1 the predicted value (FEV1%), and ratio of residual volume to total lung volume (RV/TLC). Body mass index, MLDex/in, FEV1%, FEV1/FVC, and PCT had a predictive value to AECOPD, with the combined AUC of 0.812. Conclusions HRCT imaging effectively classifies the severity of COPD, which combined with BMI, PFT, and serum PCT can predict the risk of AECOPD.

Ventricular and Atrial Ejection Fractions are Associated with Mean Compartmental Cavity Volume in Cardiac Disease.

Ejection fraction (EF) is considered to provide clinically useful information. Despite its enormous popularity, with more than 75,000 citations in PubMed, only few studies have traced the origin(s) of its foundation. This fact is surprising, as there are perhaps more papers published that criticize EF, than the number of publications that actually provide a solid (mathematical) basis for its alleged applicability. EF depends on two volume determinations, namely end-systolic volume (ESV) and end-diastolic volume (EDV). EF is defined as 1-ESV/EDV, yielding a metric without physical units. Previously we formulated a robust analytical expression for the nonlinear connection between EF and ESV. Here we extend that approach by providing a formula to illustrate that EF is strongly associated with half the sum (HS) of ESV and EDV. HS is not new, but forms a major component in the recently introduced Global Function Index. For 420 heart failure (HF) patients we found for left ventricular angio data: R(ESV, eDv) = 0.92, R(EF, ESV) = -0.90, and R(EF, HS) = -0.65. For echo (33 HF patients stages A, B, C and D): R(EF, HS) = -0.82. For the right atrium (CMRI in 21 acute myocardial infarction patients): R(EF, HS)=-0.65. For the left atrium (N=86) R (EF, hS)=-0.46. ESV indicates the level to which the ventricle is able to squeeze blood out of the cavity via pressure build-up. In contrast, EF refers to relative volume changes, not to the mechanism of pumping action. We conclude that for each cardiac compartment EF borrows its acclaimed attractiveness from the fact that for a wide patient spectrum the ESVand EDV correlate in a fairly linear manner. Attractiveness of EF features a straightforward mathematical derivation, rather than reflecting underlying physiology. Clinical Relevance - Ejection fraction (EF) is found to reflect (mean) ventricular / atrial size, and is primarily associated with end-systolic volume, which variable in turn highly correlates with diastolic volume. As a mathematical construct, EF has little affinity with "function", which is a central concept in physiology.

Importance of swim bladder inflation and effect of lighting conditions on larviculture of greater amberjack (Seriola dumerili)

Seriola species are an important target fish for the aquaculture industry, and innovative techniques for their rearing have been developed in recent years. In Experiment 1 of this work, the growth of S. dumerili larvae (with and without a swim bladder) and diurnal changes in relative swim bladder volume were compared to elucidate the significance of swim bladder inflation success in larvae. Additional trials (Experiments 2 and 3) were conducted to elucidate the effect of “fade-in” and “fade-out” lighting conditions, in which artificial light intensity was gradually increased and/or decreased. The results indicate that larvae growth without a functional swim bladder was significantly inferior, even at the early stages of development. Suitable lighting conditions, such as “fade-in,” improved viability, and at least 30 min of “fade-out” effectively induced swim bladder inflation success in the larviculture of S. dumerili.

(Digital Presentation) Characterization of Anisotropic Strain in Anelastic Material By Raman Spectroscopy

Raman spectroscopy has recently been applied for non-destructive characterization of strain in crystalline thin films. It makes use of the numerical value of the mode Grüneisen parameter γ , which equals (minus) the ratio of the relative change in the frequency of a Raman-active vibrational mode and the strain-induced relative change in the unit cell volume. In the presence of in-plane, compressive biaxial strain, aliovalent doped CeO2-films exhibit values of γ which are ~30% smaller than the literature values for the bulk ceramics under isostatic stress. This discrepancy is due in large part to the negative contribution from the anelastic (time-dependent) mechanical properties of oxygen-deficient ceria, thereby raising questions concerning the relationship between Raman mode frequency and anelastic strain. Here we propose a way to "separate" anelastic and elastic contributions to the Grüneisen parameter.500-650nm thick films , x=0.1-0.2, were deposited by RF magnetron sputtering on (100) p-Si wafers (1Ω-cm, tSi=280mm). The films (S-films) were in the fluorite phase with pronounced (111) texture and exhibited biaxial , compressive strain. The in- and out-of-plane lattice parameters (aS || , aS ⊥ ) of the S-films were determined by XRD at different sample tilt angles. The in-plane stress (σbi) in the S-films was determined by profilometry from the change in Si-wafer curvature following film deposition. From σbi and the film biaxial modulus, the elastic component of the in-plane compressive strain (ue ) was calculated (~ -0.2%).Strain-free (relaxed) R-films were obtained by partial substrate removal, forming 2 mm diameter self-supported membranes. Pronounced membrane buckling indicated that residual strain was negligible (aR || ≈ aR ^ ). From the increase in area upon substrate removal, measured with optical profilometry, the total S-film in-plane strain (ut ) was calculated from aS ||/aR-1 ≈ -0.5%. The anelastic strain component may be calculated as ua= ut-ue . The small, anisotropic strain-induced blue shift of the frequency of the F2g -phonon mode for S-films suggests that the F2g mode responds primarily to the elastic component of the strain.As a control, 430nm thick films of mechanically elastic Y2O3 were deposited by sputtering on a Si wafer covered with a 1.5 µm thick PECVD deposited SiO2 layer. This layer supported the Y2O3-films upon membrane formation, but prevented complete strain relaxation. The Y2O3-films were in the double fluorite phase with strong (222) texture and, as with the S-films, were under in-plane compressive strain. The Y2O3 S-film lattice parameters were determined by acquiring XRD-patterns at different sample tilt angles, while membrane in- and out-of-plane lattice parameters were determined with XRD in the transmission and reflection modes, respectively. The values of γ calculated from the Raman frequency of the [Fg +Ag ] peak position were close to the literature values for bulk yttria under isostatic stress.This work should serve as a sample protocol for strain characterization of doped ceria thin films. It supports the concept that the discrepancy between the behavior of Raman modes of isostatically and anisotropically strained doped ceria is related to anelasticity. Our results shed light upon strain characterization by Raman spectroscopy and may lay the foundation for future studies to elucidate selective sensitivity to various strain components.

Differential control of blood flow in masseter and biceps brachii muscles during stress

ObjectiveThe present study aimed to compare sympathetic hemodynamic effects in masticatory and limb muscles in response to different stressors. DesignTwelve healthy participants were subjected to a randomized series of stressors, including cold pressor test (CPT), mental arithmetic test, apnea, isometric handgrip (IHG) and post-handgrip muscle ischemia (PHGMI), while in the supine position. Spatially-resolved near-infrared spectroscopy was used to measure relative changes in blood volume and oxygenation (TOI) of the resting masseter and biceps muscles. Cardiac output, heart rate, and arterial blood pressure (ABP) were also monitored. ResultsExcept apnea, all tests increased ABP. Different response patterns were observed in the 2 muscles: TOI significantly increased during contralateral IHG (1.24 ± 1.17%) but markedly decreased during CPT (−4.84 ± 4.09%) and PHGMI (−6.65 ± 5.31%) in the biceps muscle, while exhibiting consistent increases in the masseter (1.88 ± 1.85%; 1.60 ± 1.75%; 1.06 ± 3.29%, respectively) (p < 0.05). ConclusionsThe results allow us to infer differential control of blood flow in head and limb muscles. In general, the masseter appears more prone to dilatation than the biceps, exhibiting opposite changes in response to painful stimuli (CPT and PHGMI). Several mechanisms may mediate this effect, including reduced sympathetic outflow to the extracranial vasculature of the head, generally exposed to lower hydrostatic loads than the rest of the body.

Abstract 3721: MTORC1/2 and HDAC1/2 inhibition as therapy for colorectal cancer with PIK3CA mutation

Abstract Introduction: Colorectal cancer (CRC) is a leading cause of cancer-related deaths. PIK3CA mutations are found in 18% of CRCs which lead to the constitutive activation of the PI3K/MTOR pathway and can promote tumorigenesis. Here, we examine the efficacy of the FDA approved inhibitors copanlisib, a PI3K/MTOR inhibitor, and romidepsin, a HDAC1/2 inhibitor, in CRC with a PIK3CA mutation. Methods: CRC mouse derived cancer organoids (MDCOs) were derived from Apc and Pik3ca mutant mice (Fc1Apcfl/+Pik3caH1047R/+). Brightfield images of the MDCOs were taken prior to treatment with copanlisib, romidepsin, or the combination and 48 hours post-treatment. The change in diameter of each organoid over the 48-hour treatment was determined. Additionally, immunoblotting was performed to confirm known targets of copanlisib and romidepsin were altered in response to drug treatment. MTORC1/2 and HDAC1/2 inhibition were also investigated in vivo. SW48 and SW48PIK3CA-H1047R (SW48PK) xenograft mice were treated with a vehicle control, copanlisib, romidepsin, or the combination therapy. Results: In the diameter analysis study, the combination therapy had the largest effect size compared to control (Glass’s Δ 2.82). Single agents copanlisib and romidepsin had smaller effect sizes (Glass’s Δ 1.75 and 2.04, respectively). Immunoblotting results indicated a decrease in phosphoAKT (Ser473) and pRPS6 (Ser235/236) in the copanlisib treated samples and an increase in H3K27 acetylation was seen in the romidepsin treated samples. There was also increased cleaved PARP, an indicator of apoptosis, in the romidepsin and combination therapy treatment groups. In vivo, SW48 xenografts showed a greater response in the combination therapy compared to either single agent therapy (median relative change in tumor volume: control=339%; combination therapy=107%(p-value&amp;lt;0.05), copanlisib=225%(p-value=0.17), romidepsin=200%). A similar trend was seen in the SW48PK xenograft mice (median relative change in tumor volume: control=241%; combination therapy=70% (p-value&amp;lt;0.05), copanlisib=132%(p-value&amp;lt;0.05), romidepsin=177%). Conclusion: MDCOs with Apc and Pik3ca mutations had an increased response to treatment with the combination therapy as compared to the single agents alone. Additionally, in vivo studies with human CRC xenografts showed enhanced inhibition of tumor growth with both MTORC1/2 and HDAC1/2 inhibition. These data demonstrate potential for this combination treatment strategy for the treatment of PIK3CA mutant CRC and this combination warrants further investigation in other models and clinically. Citation Format: Autumn M. Olson, Rebecca A. DeStefanis, Alyssa K. DeZeeuw, Susan N. Payne, Cheri A. Pasch, Linda Clipson, Dustin A. Deming. MTORC1/2 and HDAC1/2 inhibition as therapy for colorectal cancer with PIK3CA mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3721.

Abstract LB061: Evaluation of the in vivo efficacy of the B7-H3 targeting antibody-drug conjugate (ADC) DS7300a: A report fro the Pediatric Preclinical In Vivo Resting (PIVOT) program

Abstract Introduction: B7-H3 (encoded by the CD276 gene) is suggested to act as an immune checkpoint molecule and is highly expressed in some pediatric solid tumors. Monoclonal antibodies targeting B7-H3 (8H9 and MGA271) are well-tolerated but have demonstrated limited success in clinical trials. DS-7300a is a B7-H3 targeting ADC with a payload of DXd (an exatecan derivative that inhibits DNA topoisomerase I). DS-7300a has a drug-to-antibody ratio of 4 and it has shown promising early clinical activity in adults with advanced solid cancers (Johnson, Annals of Oncology 2021; 32:S583-S585). Methods: Xenograft models for several pediatric cancer types were selected for preclinical testing of DS-7300a based on the high rates of B7-H3 expression in these cancers. Models were dosed at 10 mg/kg administered intravenously every other week for two doses (Q2wk x 2). Different experimental designs were used for efficacy testing. For rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, and other pediatric solid tumors a single mouse trial (SMT) design with 40 models was used. A cohort design (N=10) was used for efficacy testing in 6 osteosarcoma models, 3 patient-derived orthotopic xenograft glioblastoma (PDOX) models, and 3 PDOX ependymoma models. For neuroblastoma models, 10 models (2 mice per model) were tested. To evaluate treatment efficacy, objective response measures based on changes in relative tumor volume were used (Houghton, Pediatr Blood Cancer 2007;49:928-940). Results: As a single agent, DS-7300a induced a statistically significant prolongation of survival in 2 of 3 orthotopic glioblastoma and 1 of 3 ependymal tumor models. DS-7300a demonstrated high efficacy (maintained complete response, complete response, and partial response) in most non-CNS models tested: 17 of 21 rhabdomyosarcomas, 5 of 7 osteosarcomas, 7 of 10 neuroblastomas and 2 of 2 Wilms tumors. For Ewing sarcoma, most models were classified as progressive disease (9 of 15). For osteosarcoma models, the log cell kill per dose values ranged from 0.95 to 2.76 indicating high activity of the agent in these models. The activity for DS-7300a followed the general pattern of protein and RNA expression levels for B7-H3/CD276 in the models, with Ewing sarcoma models showing lower expression compared to the other models. Conclusions: DS-7300a shows tumor-regressing anticancer activity across a wide range of pediatric solid tumor models. The maintained complete remissions observed for osteosarcoma models are noteworthy, as this level of response is uncommon for these models and as osteosarcoma shows the highest B7-H3 expression among pediatric cancers. The high level of preclinical activity observed for DS-7300a combined with the promising early clinical activity observed for adult patients provide strong rationale for studying DS-7300a in children with B7-H3 expressing solid tumors. Citation Format: Richard Gorlick, E. Anders Kolb, Yifei Wang, Peter Houghton, Raushan Kurmasheva, Yael Mosse, John Maris, Matthew Tsang, David Groff, Kateryna Krytska, Xiao-Nan Li, Yuchen Du, Jun Hasegawa, Nanae Izumi, Steven Neuhauser, Anuj Srivastava, Tim Stearns, Vivek Philip, Emily L. Jocoy, Jeff Chuang, Carol J. Bult, Beverly Teicher, Malcolm Smith. Evaluation of the in vivo efficacy of the B7-H3 targeting antibody-drug conjugate (ADC) DS7300a: A report fro the Pediatric Preclinical In Vivo Resting (PIVOT) program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB061.

The Prognostic Roles of Perihematomal Edema and Ventricular Size in Patients with Intracerebral Hemorrhage.

Conflicting data exist regarding the association of perihematomal edema (PHE) with outcomes after intracerebral hemorrhage (ICH). We performed a post hoc analysis of the ICH Deferoxamine trial to examine whether an early change in ventricular size (VS), as a composite measure of PHE growth and mass effect, intraventricular hemorrhage, and hydrocephalus, is a more accurate predictor of outcome than PHE measures alone. Computerized tomography scans were performed at baseline and after 72-96h. We evaluated measures of PHE and change in VS as predictors of outcome, assessed by a dichotomized modified Rankin Scale score (0-2 versus 3-6), primarily at 90days and secondarily at 30days. A multivariable logistic regression model was fitted for each predictor, with adjustment for the same confounders. A total of 248 participants were included after we excluded those requiring external ventricular drains. On univariate analyses, older age, female sex, lower Glasgow Coma Scale score and baseline temperature, greater ICH volume, absolute PHE volume, edema extension distance at presentation, lesser changes in relative PHE volume and edema extension distance, and an increase in VS were associated with poor outcome. In multivariable analyses, only the increase in VS was associated with lower odds of modified Rankin Scale scores 0-2 at 90days (odds ratio 0.927, 95% confidence interval 0.866-0.970, p = 0.001) and 30days (odds ratio 0.931, 95% confidence interval 0.888-0.975, p = 0.003). Within the context of a randomized controlled trial with standardized imaging and functional assessments, we did not find significant associations between measures of PHE and outcome but documented an independent association between early increase in VS and lower odds of good clinical outcome.

Early intervention with compression garments prevents progression in mild breast cancer-related arm lymphedema: a randomized controlled trial

Background Early diagnosis and compression treatment are important to prevent progression in breast cancer-related arm lymphedema (BCRAL). However, some mild BCRAL can be reversible, and therefore, compression treatment may not be needed. The aim of this study was to investigate the proportion of women with mild BCRAL showing progression/no progression of lymphedema after treatment with or without compression garments, differences in changes of lymphedema relative volume (LRV), local tissue water and subjective symptoms during 6 months. Also, adherence to self-care was examined. Material and methods Seventy-five women diagnosed with mild BCRAL were randomized to a compression group (CG) or noncompression group (NCG). Both groups received self-care instructions, and the CG were treated with a standard compression garment (ccl 1). Women in the NCG who progressed in LRV ≥2%, or exceeded 10% dropped out, and received appropriate treatment. The proportion showing progression/no progression of LRV, and changes in LRV was measured by Water Displacement Method. Changes in local tissue water were measured by Tissue Dielectric Constant (TDC), subjective symptoms by Visual Analogue Scale, and self-care by a questionnaire. Results A smaller proportion of LRV progression was found in the CG compared to the NCG at 1, 2 and 6 months follow-up (p ≤ 0.013). At 6 months, 16% had progression of LRV in the CG, compared to 57% in the NCG, (p = 0.001). Thus, 43% in the NCG showed no progression and could manage without compression. Also, CG had a larger reduction in LRV, at all time-points (p ≤ 0.005), and in the highest TDC ratio, when same site followed, at 6 months (p = 0.025). Subjective symptoms did not differ between the groups, except at 1 month, where the CG experienced more reduced tension (p = 0.008). There were no differences in adherence to self-care. Conclusion Early treatment with compression garment can prevent progression in mild BCRAL. Trial registration: ISRCT nr ISRCTN51918431

Intensive complex physical therapy combined with intermittent pneumatic compression versus Kinesio taping for treating breast cancer-related lymphedema of the upper limb: A randomised cross-over clinical trial.

ObjectiveThe objective of this study is to compare the effectiveness of complex physical therapy combined with intermittent pneumatic compression (CPT + IPC) versus Kinesio taping (KT) for breast cancer‐related lymphedema.MethodsA cross‐over clinical trial was conducted in 43 women with lymphedema. All participants received two interventions: CPT + IPC and KT, both lasting 3 weeks and a washout period. The main outcome variable was the relative volume change (RVC). The secondary variables were Satisfaction Questionnaire about Textile Therapeutic Devices used for Breast Cancer‐Related Lymphedema, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, motion range of upper limb and lymphedema‐related symptoms.ResultsThe RVC reduction was greater with CPT + IPC (−2.2%, SD = 4.7) versus KT (−0.9%, SD = 1.7) (P = 0.002). KT was more satisfactory than multilayer bandaging (8.9 points difference, P < 0.001) and improved DASH score more than CPT + IPC (14.3 points difference, P = 0.002). Regarding motion ranges, only shoulder movements showed significant improvement with CPT + IPC compared with KT (differences between 5.6° and 11.4°). Of the symptoms assessed, only pain reduction showed a significant improvement with KT versus CPT + IPC (0.5 points, P = 0.035).ConclusionsCPT + IPC achieved higher RVC and greater improvement in th shoulder motion range than KT. Conversely, KT was more satisfactory than multilayer bandaging, obtained better DASH scores and relieved pain more than CPT + IPC.Clinical RegistrationClinicalTrial registration number: NCT03051750 (date of registration 14 February 2017).