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Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) has received increased attention because of its novel treatment options. Carpal tunnel syndrome (CTS) is known as early symptoms in transthyretin amyloidosis (ATTR) preceding cardiac involvement and one of the “red flags” for ATTR-CM. A 64-year-old man underwent carpal tunnel release for carpal tunnel syndrome at 62 years. He was diagnosed with wild-type ATTR due to deposition of transthyretin (TTR) amyloid in flexor tenosynovium specimens and no TTR gene mutation. Examination for detection of cardiac involvement was performed after the operation, and there were no definitive findings of ATTR-CM; however, an early stage of ATTR-CM remained a possibility. Serial image evaluation and biomarker analysis revealed positive findings for ATTR-CM, and we performed an endomyocardial biopsy, resulting in the detection of amyloid deposition. He was diagnosed with ATTRwt-CM 2 years after the operation, and even then, he had no heart failure symptoms. Early diagnosis and treatment are important for the improvement of clinical outcomes in patients with ATTRwt-CM. TTR deposition in the ligaments or tendons is often observed in patients with CTS and should be considered at high risk of future ATTR-CM. Serial follow-up of these patients may enable the diagnosis of preclinical ATTR-CM.

To predict the mixed damage modes of unidirectional fiber-reinforced polymer (FRP) laminates under dynamic loading, an FEM-based peridynamic model is introduced in this paper. Based on its geometric structure and material composition, a long fiber lamina is considered a transversely isotropic medium as a result of homogenization at the meso-scale. The laminated structure is modeled by stacking surface mesh layers with arbitrary fiber angles along the thickness direction. The peridynamic bonds between Gauss points connect the separated elements. These bonds are classified as inner-layer bonds and inter-layer bonds. To represent the anisotropy of a laminate, the micro-elastic modulus of the inner-layer and inter-layer bonds is calculated from the anisotropic engineering material constants separately. To capture complex failure behaviors of laminate structures, an empirical damage model is proposed for the tension/ compression breakage of peridynamic bonds. This damage model can control the in-plane and delamination failure process. Benchmark tests are conducted to validate the elastic response of laminates under dynamic loading. In terms of damage analysis, the proposed model can capture the complex damage modes and resistive force of laminate structures.

The Automated Fiber Placement (AFP) is the technology for automated layup of multiple narrow prepreg tapes in CFRP (Carbon Fiber Reinforced Plastics) manufacturing of structural components for aircraft. Because most AFP devices cut the material perpendicular to the feed direction, geometrically complex layup can result in localized gaps and overlaps that can affect the mechanical properties of the molded product. The bending modulus of prepreg tapes is the dominant factor for defect formation in the layup process. For the layup using CFRTP (Carbon Fiber Reinforced Thermoplastics) tapes, the material is heated during the tape layup and thus the temperature variation and distribution during forming have a large effect on the bending modulus of prepreg tapes [1]. In this study, we modeled the laminate with internal defects made by the AFP process, and we performed a coupled structural thermal analysis for the gap elimination when the out-of-plane pressure was applied, considering the temperature-dependent material properties of CFRTP. We showed a relationship between the bending stiffness of the layer above the gap and defect formation in CFRTP.

Background: Using transthoracic echocardiography, including 2D speckle tracking imaging (STI), this study examined cardiac function after domino liver transplantation (DLT) with liver grafts explanted from patients with hereditary amyloidogenic transthyretin amyloidosis. Methods and Results: In all, 14 patients who underwent DLT at Kumamoto University Hospital and for whom 2D STI information was available were enrolled in the study; time-dependent echocardiographic changes were evaluated in 7. Although left ventricular (LV) systolic and diastolic function did not differ between the pre- and post-DLT periods (mean [±SD] 5.4±1.0 years after DLT), there were significant (P−14%) than preserved basal LS (57.2±3.5 vs. 39.6±16.0 years; P−14%; odds ratio 28.39, 95% confidence interval 1.89–427.45, P

Background Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is receiving increasing attention due to the availability of novel treatment options. Carpal tunnel syndrome (CTS) and lumbar spinal canal stenosis are known early symptoms of transthyretin (TTR) amyloidosis preceding the cardiac involvement and are considered as ‘Red Flags’ for transthyretin amyloid cardiomyopathy (ATTR-CM). Case summary A 67-year-old man with a history of lumbar spinal canal stenosis for the last 10 years, right rotator cuff tears for the last 4 years, and bilateral CTS for the last 1 year was scheduled for orthopaedic surgery for lumbar spinal canal stenosis. Investigations revealed severe left ventricular hypertrophy and hypertroponinaemia, which were suggestive of cardiac amyloidosis. Cardiac magnetic resonance imaging and 99mTc-labelled pyrophosphate scintigraphy demonstrated positive findings for ATTR-CM. Transthyretin deposition was found in both the myocardium and the yellow ligamentum excised during surgery. There was no transthyretin mutation on genetic testing. The final diagnosis was ATTRwt-CM. Discussion Transthyretin deposition in the ligaments or tendons has been observed in a number of patients with CTS, spinal canal stenosis, and rotator cuff tears. These orthopaedic diseases are predictive for the future occurrence of ATTR-CM. In addition, the coexistence of these multiple diseases might strongly predict ATTR-CM. This knowledge needs to be shared with orthopaedicians and cardiologists for the early diagnosis of ATTR-CM.

BACKGROUND We previously reported that a high score (2 or 3 points) according to the Kumamoto criteria, a combination of high-sensitivity cardiac troponin T (hs-cTnT) ≥0.308 ng/mL, the length of QRS ≥ 120 ms in electrocardiogram, and left ventricular (LV) posterior wall thickness ≥ 13.6 mm, increases the pretest probability of 99m Tc-labeled pyrophosphate (99m Tc-PYP) scintigraphy in patients with suspected transthyretin amyloid cardiomyopathy (ATTR-CM). However, some patients with a low score (0 or 1 point) show positive findings on 99m Tc-PYP scintigraphy. Therefore, we evaluated the usefulness of additional examinations, including echocardiographic assessment of myocardial strain, to raise the pretest probability of 99m Tc-PYP scintigraphy for these patients. METHODS AND RESULTS We examined 109 consecutive patients aged ≥70 years with low scores according to the Kumamoto criteria who underwent 99m Tc-PYP scintigraphy. Nineteen patients (17%) had positive 99m Tc-PYP scintigraphy findings. The relative apical longitudinal strain (LS) index (apical LS/ basal LS + mid LS) (RapLSI) was significantly higher in patients with positive than negative 99m Tc-PYP scintigraphy findings (1.04 ± 0.37 vs 0.70 ± 0.28, P

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This study was performed to investigate whether right ventricular global longitudinal strain (RV-GLS) provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM).Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 111 patients who had enough information for two-dimensional speckle tracking imaging were retrospectively analyzed. During a median follow-up of 615 days, 26 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group were significantly older (81.1 ± 7.4 years vs. 78.2 ± 6.2 years, p = 0.009) and had significantly higher interventricular septal thickness in diastole (16.6 ± 3.1 mm vs. 15.3 ± 2.4 mm, p = 0.048), lower RV-GLS (10.9 ± 2.7% vs. 12.8 ± 3.5%, p = 0.010), and lower right ventricular free wall longitudinal strain (RVFWLS) (13.1 ± 3.3% vs. 15.5 ± 3.8%, p = 0.004). In the univariate Cox proportional hazard analysis, age, left atrial volume index (LAVI), RV-GLS, and RVFWLS were significantly associated with cardiovascular death [age, hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.02-1.19, p = 0.010; LAVI, HR, 1.02; 95% CI, 1.00-1.03, p = 0.009; RV-GLS, HR, 0.86; 95% CI, 0.75-0.97, p = 0.017; RVFWLS, HR 0.89; 95% CI, 0.79-1.00; p = 0.041]. Multivariable Cox proportional hazard analysis showed RV-GLS was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (HR, 0.86; 95% CI, 0.74-0.99; p = 0.038). Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for cardiovascular death was 0.668 and that the best cut-off value of RV-GLS was 11.59% (sensitivity, 69.2%; specificity, 63.5%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low RV-GLS (11.59%) had a significantly higher probability of total cardiovascular death (p = 0.004) and heart failure-related hospitalization (p = 0.013).RV-GLS has significant prognostic value in patients with ATTRwt-CM and provides greater prognostic power than conventional echocardiographic findings.

Background The staging systems for transthyretin amyloid cardiomyopathy (ATTR-CM) by high sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR) are established. However, this system is not validated in Japan. Purpose The aim of study was to validate and modify the predicting system by BNP, hs-cTnT and eGFR of prognosis for Japanese patients with ATTRwt-CM. Method We evaluated in 158 consecutive patients with wild-type ATTR-CM. Univariate analysis revealed that increased hs-cTnT and B-type natriuretic peptide (BNP) levels and impaired renal function at diagnosis were associated with poor prognosis. We defined best cutoff value as follows by ROC curve analysis; hs-cTnT >0.0565 ng/mL, BNP >285 pg/mL and eGFR Result As shown figure, high score was associated with increased all-cause mortality and heart failure rehospitalization (log rank; P Conclusion This simple scoring system by hs-cTnT, BNP and eGFR, was useful for predicting prognosis in patients with wild-type ATTR-CM. Funding Acknowledgement Type of funding sources: None.

BACKGROUND A significant male predominance has been reported in wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). Hence, female cases of ATTRwt-CM are overlooked, and sex-related differences in ATTRwt-CM remain unclear. This study aimed to examine sex-related differences in clinical characteristics and diagnostic approaches in ATTRwt-CM. METHODS We retrospectively analyzed 199 consecutive patients who were diagnosed with ATTRwt-CM and evaluated sex-related differences in clinical characteristics, imaging parameters, biomarkers, and diagnostic approaches. RESULTS Twenty-nine patients (15%) were female. These female patients were significantly older at diagnosis (77.1 ± 6.5 years vs. 82.9 ± 4.8 years; p

Aims This study was performed to investigate whether left atrial (LA) strain by echocardiography provides prognostic information in patients with wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM). Methods and results Among 129 patients who were diagnosed with ATTRwt‐CM at Kumamoto University Hospital from December 2002 to December 2019, 113 patients who had enough information for two‐dimensional speckle tracking echocardiography were enrolled in this study. During a median follow‐up of 668 days, 28 cardiovascular deaths occurred. Compared with patients in the non‐event group, those in the cardiovascular death group were significantly older (81.5 ± 7.4 vs. 78.1 ± 6.1 years, P

BACKGROUND A recent study revealed a high prevalence of transthyretin (TTR) cardiac amyloidosis (CA) in elderly patients. 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy is a remarkably sensitive and specific modality for TTR-CA, but is only available in specialist centres; thus, it is important to raise the pretest probability. The aim of this study was to evaluate the characteristics of patients with 99 mTc-PYP positivity and make recommendations about patient selection for 99 mTc-PYP scintigraphy.Methods and Results:We examined 181 consecutive patients aged ≥70 years who underwent 99 mTc-PYP scintigraphy at Kumamoto University Hospital between January 2012 and December 2018. Logistic regression analyses showed that high-sensitivity cardiac troponin T (hs-cTnT) ≥0.0308 ng/mL, left ventricular posterior wall thickness ≥13.6 mm, and wide QRS (QRS ≥120 ms) were strongly associated with 99 mTc-PYP positivity. We developed a new index for predicting 99 mTc-PYP positivity by adding 1 point for each of the 3 factors. The 99 mTc-PYP positive rate increased by a factor of 4.57 for each 1-point increase (P

The measurement of the fracture toughness of fiber reinforced composites at high rates of loading is still, despite years of research, not well established. This can be related to challenges in applying appropriate high rate loading on the specimen, accurately measuring the load, and in-situ determination of the crack length. In this work these challenges are addressed by using a direct wedge-on-specimen type loading of a double cantilever beam (DCB) specimen, high resolution optical deformation tracking, and a beam theory based analysis of the specimen deflection and crack length. This approach results in symmetric mode I opening of the crack and a robust analytical determination of the fracture toughness without the need to measure the external forces acting on the specimen nor to visually estimate the crack length. Tests carried out on carbon fiber reinforced epoxy composite at quasi-static and high rates (relative velocity up to 15 m/s) show the validity of the approach.

Aims Bleeding is a serious complication in patients with continuous‐flow left ventricular assist device (CF‐LVAD). Acquired von Willebrand syndrome (AVWS; type 2A) develops because of high shear stress inside the pumps and is a cause of bleeding complication. Although von Willebrand factor (vWF) multimer analysis is useful for diagnosing AVWS, it is only performed in specialized research institutes. A novel microchip flow chamber system, the total thrombus‐formation analysis system (T‐TAS), is a point‐of‐care system to evaluate the thrombus‐formation process and useful for monitoring platelet thrombus‐formation capacity in patients receiving antiplatelet therapy and the diagnosis and evaluation of the clinical severity of von Willebrand disease type 1. However, little is known about the association between AVWS and platelet thrombus‐formation capacity evaluated by T‐TAS in patients with CF‐LVAD. We aimed to evaluate the utility of T‐TAS for easy detection of AVWS in patients with CF‐LVAD. Methods and results We simultaneously evaluated the vWF large multimers and T‐TAS parameters in four consecutive patients with axial‐type CF‐LVAD and eight control patients treated with aspirin and warfarin. vWF large multimer index was defined as the proportion of large multimers in total vWF derived from a normal control plasma. T‐TAS analyses different thrombus‐formation processes using two microchips with different thrombogenic surfaces. PL24‐AUC10 levels in the platelet (PL) chip are highly sensitive for platelet functions, while AR10‐AUC30 levels in the atheroma (AR) chip allow the assessment of the overall haemostatic ability. vWF large multimer index and T‐TAS parameters were decreased in all patients with CF‐LVAD. The mean PL24‐AUC10 level (5.4 ± 2.9 vs. 219 ± 67; P

In this paper, some large automotive parts with complex shapes are produced to report the results of our efforts to develop press molding technologies for thermoplastic carbon fiber-reinforced plastic (CFRTP). Members of industry, academia, and the government collaborated to realize this project. The project includes a molding experiment, CAE analysis, and material strength measurements. In the material test, a tensile test, bending test, heat distortion test, and torsion test are carried out to produce several stress-strain curves. Applying the new analytical model in the simulation shows that accuracy is improved. As a result, by measuring the temperature change during the forming of complex shapes, a large automotive part with a complex shape was successfully molded in a short time. Other productivity improvements are also reported on.

Background In the recent past, transthyretin cardiac amyloidosis (TTR-CA) is recognized as an important cause of heart failure with preserved ejection fraction, and diagnostic utility of 99mTc-pyrophosphate (99mTc-PYP) scintigraphy in TTR-CA has been established. However, pathological evaluation is still the basis to confirm diagnosis. Subcutaneous tissue and gastrointestinal tract biopsy are useful examinations alternative to endomyocardial biopsy. Nevertheless, the positive ratio of amyloid deposition in these organs is not fully evaluated based on recent non-invasive diagnostic criteria. Purpose Our aim was to evaluate the diagnostic sensitivity of tissue biopsy in TTR-CA patients diagnosed by 99mTc-PYP scintigraphy. Methods We retrospectively evaluated 124 consecutive TTR-CA patients [wild-type (ATTRwt): 90, hereditary (hATTR): 34] who were diagnosed by positive findings of 99mTc-PYP scintigraphy (visual score 2 or 3) between June 2002 and January 2019 at our institute. Results A total of 114 patients underwent tissue biopsy at least one organ. Amyloid was detected on Congo red staining of subcutaneous tissue (43/97: 44%), gastrointestinal tract (52/78: 67%) and heart (78/79: 99%), respectively. Among 70 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsy, amyloid was detected at least one specimen in 57/70 (81%). Compared to hATTR CA patients, ATTRwt CA patients had lower positive ratio of subcutaneous tissue (81% vs. 27%) and gastrointestinal tract (73% vs. 63%) biopsy. Conclusion Non-invasive diagnostic criteria of TTR-CA had excellent sensitivity of amyloid deposition in heart. The diagnostic sensitivity of subcutaneous tissue and gastrointestinal tract biopsy was lower in ATTRwt CA compared to hATTR CA. Combination of subcutaneous tissue and gastrointestinal tract biopsy was useful for pathological confirmation of amyloid deposition without endomyocardial biopsy.

A 49-year-old man complained of sudden upper abdominal pain but was not given a definitive diagnosis. The day after he was discharged, he noticed left chest pain. An in-depth electrocardiogram indicated acute myocardial infarction, and emergent coronary angiography revealed 99% stenosis of his left coronary artery. An intravascular ultrasound revealed spontaneous coronary artery dissection (SCAD), and the lesion was successfully stented. In an atherosclerosis screening, superior mesenteric artery dissection (SMAD) was confirmed, after which the lesion was successfully stented. This case suggests that SCAD and SMAD might have similar pathological backgrounds.

We discuss the large mass hierarchy problem in a braneworld model which represents our acceleratively expanding universe. The Randall-Sundrum (RS) model with warped one extra dimension added to flat 4-dimensional space-time cannot describe our expanding universe. Here, we study instead the de Sitter thin brane model. This is described by the same action as that for the RS model, but the 4-dimensional space-time on the branes is $\rm dS_4$. We study the model for both the cases of positive 5-dimensional cosmological constant $\Lambda_5$ and negative one. In the positive $\Lambda_5$ case, the 4-dimensional large hierarchy necessitates a 5-dimensional large hierarchy, and we cannot get a natural explanation. On the other hand, in the negative $\Lambda_5$ case, the large hierarchy is naturally realized in the 5-dimensional theory in the same manner as in the RS model. Moreover, another large hierarchy between the Hubble parameter and the Planck scale is realized by the ${\mathcal O}(10^2)$ hierarchy of the 5-dimensional quantities. Finally, we find that the lightest mass of the massive Kaluza-Klein modes and the intervals of the mass spectrum are of order $10^2\,\rm GeV$, which are the same as in the RS case and do not depend on the value of the Hubble parameter., Comment: 24 pages, 6 figures. v5: published version

Rollover tests are performed to design the algorithms for deployment of countermeasures to mitigate occupant ejection in rollover situations. The ditch fall-over test is one of the rollover test methods in which a vehicle on a steep slope, representing a ditch embankment, is subjected to a forced steering operation that results in a turnover. An accurate prediction method is needed to determine the specifications of the ditch fall-over test equipment and test conditions because a test-based trial-and-error process involves high cost of performing repeated experiments and preperation for various types of related test equipment. This paper presents a newly developed numerical simulation method for simulating vehicle behavior in ditch fall-over tests. The vehicle model used in the simulation incorporates a finite element tire model for calculating the contact forces to a steep slope in a rollover situation characterized by large contact patch deformation with very large camber angles relative to the slope, an operating condition that ordinary vehicles cannot handle. The vehicle model also includes the suspension systems, steering system and inertial properties of the vehicle. Under various test conditions, the simulation results agreed well with those of actual ditch fall-over test data to judge whether turnover occurred or not and also the dynamic response such as vehicle roll rate. Simulations were conducted to investigate the test equipment specifications and test conditions for a vehicle. It was found that the slope angle, the friction coefficient of the slope, initial vehicle velocity and the sectional shape of the slope at the top influence vehicle turnover behavior. Language: en