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Objective Chinese informal caregivers experience burden due to their caregiving responsibilities that violate their belief of reciprocal parent-child relationship, but little is known about this burden and coping processes among Chinese. It is believed that internal coping (i.e., self-reliance) and external coping (i.e., seeking help from others) better captured cultural characteristics of coping styles observed among Chinese. Thus, the aim of this study was to estimate the prevalence of mental ill health, identify correlates, investigate the impact of caregiving burden on mental health, and explore the potentially moderating role of two coping strategies. Design A purposive sample of 234 informal caregivers of family with intellectual or mental disability in Macao (SAR), China, from August to September 2018 was investigated. Methods DASS-21, Caregiving Burden Inventory (CBI), Perceived Difficulty Scale (PD), and a modified Chinese Coping Scale were used. Multiple regression analyses were conducted. Results CBI and PD were associated with depression, anxiety, and stress. Whereas internal coping buffered the effect of PD on depression and anxiety, external coping exacerbated the effect of PD on anxiety and the effect of CBI on depression and anxiety. Conclusion Poor mental health among caregivers is associated with greater caregiving challenges and burdens. Internal coping helped to buffer but external coping worsened the effect of burdens on mental health outcomes. Interventions that improve internal coping and mental health might be helpful for ageing informal caregivers.

Gastric cancers are highly prevalent in both the East and the West, although they differ in aetiology and prognostic outcome. Management of gastric cancer from screening to definitive treatment varies substantially between Eastern and Western countries and regions, owing to numerous factors, including government incentives to carry out population-wide screening programmes to detect early disease, differences in clinical and biological tumour behaviours and responsiveness to treatment, patient accessibility to effective treatment, etc. This review highlights and contrasts the differences in tumour aetiology and histology, as well as the management approaches between the East and the West, which gives important insights and inspirations on future international multicentre research collaboration to combat this dreadful malignancy.

Reinforced concrete (RC) walls play an important role in resisting earthquakes, so understanding the lateral load-deformation response of an RC wall subjected to an axial load, shear, and moment is essential to nonlinear structural analysis. In this study, the moment-bending deformation response of an RC wall under an axial load and moment is obtained from moment–curvature analysis using the wall’s proper plastic hinge length. Furthermore, modified compression-field theory, adjusted according to the height–length ratio of the wall, is used to calculate the shear–shear deformation response of the wall under an axial load and shear. By integrating the moment-bending deformation and the shear–shear deformation responses, the lateral load-deformation response of the RC wall under axial load–moment–shear interaction can be reasonably determined. To confirm the reliability of the proposed method, experimental results for 67 RC walls are compared with analysis results from the proposed method. The statis...

Life-cycle cost analysis has been employed as an optimal decision-support tool for management of infrastructures over their lifespan. This article applies life-cycle cost analysis to find an optimal importance factor for a fire department building and shows how this factor differs from what is suggested by various building codes. This analysis comprises computing the life-cycle cost for each of an ascending sequence of importance factors and finding an importance factor that makes the life-cycle cost close to the minimum. The life-cycle cost is considered to be composed of the initial construction cost and the earthquake loss. In particular, this article considers earthquake loss, including the indirect economic loss caused by building function interruption and the direct economic loss that recent studies often consider.

Summary Histone deacetylases (HDACs) and RNA polymerase III (POLR3) play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A) and an inhibitor of Polr3 (ML-60218) synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.

Histone deacetylases (HDACs) play important roles in the epigenetic control of development, and aberrant expression of HDACs has been implicated in human diseases including cancer. Among the mammalian HDACs, HDAC1 has been extensively studied, but its role in exocrine pancreatic morphogenesis and cancer is still poorly understood. The goal of this study is to determine the functional role of HDAC1 in normal development of exocrine pancreas using zebrafish as the model organism as well as in human pancreatic adenocarcinoma. The zebrafish germline loss-of-function mutation hdac1(hi1618) caused impaired cell cycle progression in pancreatic epithelia, resulting in growth arrest and dysmorphogenesis of exocrine pancreas. In human pancreatic adenocarcinoma tissues and cell lines, HDAC1 was expressed at variably elevated levels. RNA interference-induced silencing of HDAC1 diminished proliferation of the cancer cells and cell cycle progression. The proliferative arrest in the developing exocrine pancreas and pancreatic cancer cells was associated with up-regulated expression of the cyclin-dependent kinase inhibitors and the sonic hedgehog signaling components. This study indicates that HDAC1 is required for pancreatic epithelial proliferation in development and cancer. We hypothesize that aberrant expression of HDAC1 modulates the developmental and signaling pathways in exocrine pancreatic epithelia and consequently the genes required for cellular proliferation during development and progression of pancreatic neoplasia.

For a bi-linear SDOF system subjected to a specific wave form of the ground acceleration, the unique yielding pseudo spectral acceleration and spectral displacement (Say, Sdy) together with various inelastic responses (Sai, Sdi) can be obtained via nonlinear time history analyses, respectively, by tuning the different levels of peak ground acceleration as various input ground motions. Meanwhile, the corresponding elastic responses (Sae, Sde) of a linear SDOF system with the identical mass, viscous damping and elastic stiffness as those of the bi-linear one can also be determined through linear time history analyses under the same excitations. The proposed NSAD format shown on the diagram of the elastic force ratio, Ω=Sae/Say I Say, versus the ductility ratio, (μ= (Sdi/Sdy), is a dimensionless plot of the seismic demands suitable to the engineers who are familiar with the conventional force-based design using linear structural analysis. In this paper, more than two hundred ground motions recorded in the Chi-Chi earthquake, Taiwan (1999) were chosen as the seismic inputs for the establishment of the NSAD format. The characteristics and applications of the NSAD format on the performance-based seismic design of the bridge structures were discussed, and realistic procedures for the methodology were proposed.The results obtained shows that the NSAD format can help the engineers evaluate the multiple-level seismic demands not only with a well precision but also with a great convenience.

For any places located in zones with high seismic risk, seismic damage assessment of buildings is a crucial issue. In the past few years, much attention has been paid to the concept of performance‐based assessment due to ATC‐40. However, its tedious procedure and deficiency in precision have left room for improvement. In the present paper, a modified procedure is introduced. It is expected to improve the efficiency as well as accuracy of the assessment. The main idea of the modification is to treat the performance points on the structural capacity curve as input, and subsequently determine the corresponding seismic demands of RC structures. The proposed approach is also capable of finding the correlations between peak ground acceleration (PGA) and various structural performances. On the other hand, it is well known that the accuracy of pushover analysis is greatly affected by the proper setting of the plastic hinges. Here, an algorithm for determining plastic hinges with respect to three well‐kno...

This paper proposes a realistic approach to pushover analyses of reinforced concrete (RC) structures with single column type and frame type. The characteristic of plastic hinge of a single RC column subjected to fixed axial load was determined first according to column`s three distinct failure modes which were often observed in the experiments or earthquakes. By using the determined characteristic of plastic hinge, the pushover analyses of single RC columns were performed and the analytical results were investigated to be significantly consistent with those of cyclic loading tests. Furthermore, a simplified methodology considering the effect of the variation of axial force for each RC column of the frame structure during pushover process is proposed for the first time. It would be helpful in performing pushover analysis for the structures examined in this study with efficiency as well as accuracy.

Quatre colonnes de beton arme pleine grandeur, comme celles utilisees dans les bâtiments scolaires, ont ete coulees et testees sous une charge cyclique inversee. Les resultats d'essais des deux colonnes non modifiees confirment que les comportements d'hysteresis d'une colonne sont considerablement ameliores si des conditions de conception sismique speciales sont utilisees en plus des exigences de conception generales au lieu d'utiliser uniquement les exigences de conception generales. Bien que la resistance et la rigidite transversales n'aient pas augmente, la ductilite augmente et le pincement diminue dans les cycles d'hysterese. Nous avons egalement trouve que la colonne conforme aux exigences de conception generales peut etre adaptee avec succes en l'enroulant soit avec des tissus en fibre de carbone ou avec des plaques profilees en « L » avec polymere renforce de fibres de carbone si son confinement lateral est augmente au meme niveau que celui de la conception en se basant sur les conditions de conception sismiques speciales. Cette adaptation de confinement lateral est efficace pour ameliorer la ductilite d'une colonne et attenuer la degradation de la resistance, la degradation de la rigidite et le pincement dans les cycles d'hysterese, bien que la resistance et la rigidite de la colonne n'aient pas augmente.

Functional MR (fMR) imaging techniques based on blood oxygenation level dependent (BOLD) effects were developed and applied to a rat brain tumor model to evaluate the potential utility of the method for characterizing tumor growth and regression following treatment. Rats bearing 9L brain tumors in situ were imaged during inhalation of room air and after administration of 100% oxygen + acetazolamide (ACZ) injected 15 mg/kg intravenously. Pixel-to-pixel fMR maps of normalized signal intensity change from baseline values were calculated from T2 weighted spin echo (SE) images acquired pre- and post- oxygen + ACZ administration. Resultant fMR maps were then compared to gross histological sections obtained from corresponding anatomical regions. Regions containing viable tumor with increased cellular density and localized foci of necrotic tumor cells consistent with hypoxia were visualized in the fMR images as regions with decreased signal intensities, indicating diminished oxyhemoglobin concentration and blood flow as compared to normal brain. Histological regions having peritumor edema, caused by increased permeability of tumor vasculature, were visualized in the fMR images as areas with markedly increased signal intensities. These results suggest that fMR imaging techniques could be further developed for use as a non-invasive tool to assess changes in tumor oxygenation/hemodynamics, and to evaluate the pharmacologic effect of anti-neoplastic drugs.

Purpose. Malignant brain tumors represent a serious therapeutic challenge, and survival often is low. We investigated the delivery of doxorubicin (DXR) to rat brain tumors in situ vialiposomes, to test the hypothesis that intact liposomes undergo deposition in intracranial tumor through a compromised blood-tumor vasculature. Both therapeutic effect and intra-tumor drug carrier distribution were evaluated to identify variables in carrier-mediated delivery having impact on therapy. Methods. The rat 9L gliosarcoma tumor was implanted orthotopically in Fischer 344 rats in the caudate-putamen region. The tumor-bearing rats were treated with DXR, either free or encapsulated in long-circulating, sterically-stabilized liposomes. Anti-tumor efficacy was assessed by survival time. In parallel, liposomes labeled with a fluorescent phospholipid analog were injected into tumor-bearing rats. At predetermined intervals, the brains were perfused with fixative, sectioned, and imaged with laser scanning confocal microscope (LSCM) to investigate the integrity of the tumor vascular bed and the intratumor deposition of liposomes. Results. Free DXR given in 3 weekly iv injections was ineffective in increasing the life span of tumor-bearing rats at cumulative doses ≤17 mg/kg, and at the highest dose (17 mg/kg) decreased survival slightly, compared to saline-treated controls. In contrast, DXR encapsulated in long-circulating liposomes mediated significant increases in life span at 17 mg/kg. Rats showed a 29% percent increase in median survival, respectively, compared to saline-control animals. The delay of treatment after tumor implantation was a major determinant of therapeutic effect. Fluorescent liposomes were deposited preferentially in tumor rather than normal brain, and were distributed non-uniformly, in close proximity to tumor blood vessels. Conclusions. Liposomes can be used to enhance delivery of drugs to brain tumors and increase therapeutic effect. The therapeutic effect may arise from release of drug from liposomes extravasated in discrete regions of the tumor vasculature and the extravascular space.

Breast density has been established as an independent risk factor associated with the development of breast cancer. It is known that an increase of mammographic density is associated with an increased cancer risk. Since a mammogram is a projection image, different body position, level of compression, and the x-ray intensity may lead to a large variability in the density measurement. Breast MRI provides strong soft tissue contrast between fibroglandular and fatty tissues, and three-dimensional coverage of the entire breast, thus making it suitable for density analysis. To develop the MRI-based method, the first task is to achieve consistency in segmentation of the breast region from the body. The method included an initial segmentation based on body landmarks of each individual woman, followed by fuzzy C-mean (FCM) classification to exclude air and lung tissue, B-spline curve fitting to exclude chest wall muscle, and dynamic searching to exclude skin. Then, within the segmented breast, the adaptive FCM was used for simultaneous bias field correction and fibroglandular tissue segmentation. The intraoperator and interoperator reproducibility was evaluated using 11 selected cases covering a broad spectrum of breast densities with different parenchymal patterns. The average standard deviation for breast volume and percent density measurements was in the range of 3%–4% among three trials of one operator or among three different operators. The body position dependence was also investigated by performing scans of two healthy volunteers, each at five different positions, and found the variation in the range of 3%–4%. These initial results suggest that the technique based on three-dimensional MRI can achieve reasonable consistency to be applied in longitudinal follow-up studies to detect small changes. It may also provide a reliable method for evaluating the change of breast density for risk management of women, or for evaluating the benefits∕risks when considering hormonal replacement therapy or chemoprevention.

The response of multi-degree-of-freedom (MDOF) structures with sliding supports is studied. The problem of sliding structures is a discontinuous one in that different numbers of equations of motion with varying forcing functions are required for the sliding and non-sliding phases. The numerical difficulties involved in this regard in an incremental finite element analysis can be circumvented through the introduction of a fictitious spring for the sliding support. Such a treatment enables one to study the higher mode effects on MDOF sliding structures under the excitation of harmonic or earthquake motions. The dynamic characteristics of MDOF sliding structures will be highlighted in the analysis of a four-storey shear building with sliding support.

A position-based impedance controller for excavator-type manipulators has been developed in our laboratory. This paper describes the proposed impedance controller and presents supporting experimental results. First, the problem of impedance control for a single hydraulic actuator is addressed and a method is presented for stability analysis. Steady-state position and force tracking of the closed loop system is also studied. Then, the desired impedance of the end-effector (bucket of the excavator) is mapped onto the hydraulic cylinders using the arm Jacobian and accurate estimates of the arm inertial and gravity terms. A nonconservative method is presented for predicting stability of the multivariable closed loop system. Experiments with an instrumented mini excavator (for the single cylinder case) show that the designed impedance controller has a good performance.

This study was designed to assess the efficacy and safety of substituting cisplatin with oxaliplatin in the DHAP (dexamethasone, cytarabine and cisplatin) regimen for patients with relapsed or refractory non-Hodgkin's lymphoma. Twenty-four evaluable patients with intermediate or high-grade non-Hodgkin's lymphoma were treated at 3-weekly intervals with oxaliplatin (130 mg/m2, d 1), cytarabine (2 g/m2 for two doses, d 2) and dexamethasone (40 mg, d 1-4). The median age of the patients was 58 (range 18-70). Histological subtypes were diffuse large B cell, 20; mantle cell, two; anaplastic large cell, one; and peripheral T cell, one. The overall objective response rate (RR) was 50% [95% confidence interval (CI) = 29-71%] including four complete responses and eight partial responses. RR for those patients treated at first relapse was higher than those treated at second and subsequent relapse (77% versus 29%). Grade 3 and 4 toxicity was mainly haematological: anaemia 17%, neutropenia 75% and thrombocytopenia 75%. No grade 4 non-haematological toxicity was reported. No significant renal and neurotoxicity was demonstrated. Median survival was 10.6 months. Probabilities of 1-year progression-free survival and overall survival were 47% (95% CI = 26-66%) and 50% (95% CI = 23-72%) respectively. In conclusion, dexamethasone, cytarabine and oxaliplatin (DHAX) is a novel combination in salvage therapy for relapsed or refractory non-Hodgkin's lymphoma. It has clinically significant activity with an acceptable toxicity profile. Lack of renal toxicity makes DHAX an attractive cytoreductive regimen before high-dose chemotherapy.

We present a novel method to encapsulate and formalize haptic interaction in a compact systematic format using hierarchical finite state machines (HFSMs). HFSMs capture both reality-based and synthesized haptic interactions. The lowest level states in the hierarchy are impedances implemented by the haptic device. Transitions between states are governed by inequalities defining geometric and dynamic constraints. This model is compatible with other haptic rendering techniques and can be used as a low level application programming interface. We will describe the format and implementation and illustrate the approach with an example. Experimental results with a three-degree-of-freedom planar haptic interface are also presented.