Association between antenatal corticosteroid treatment and severe adverse events in pregnant women.

BACKGROUND: Antenatal corticosteroids are considered the standard of care for pregnant women at risk for preterm birth, but studies examining their potential risks are scarce. We aimed to estimate the associations of antenatal corticosteroids with three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding, in pregnant women. METHODS: Of 2,157,321 pregnant women, 52,119 at 24 weeks 0/7 days to 36 weeks 6/7 days of gestation were included in this self-controlled case series study during the study period of 2009-2018. We estimated incidence rates of three severe adverse events: sepsis, heart failure, and gastrointestinal bleeding. Conditional Poisson regression was used to calculate incidence rate ratios (IRRs) for comparing incidence rates of the adverse events in each post-treatment period compared to those during the baseline period among pregnant women exposed to a single course of antenatal corticosteroid treatment. RESULTS: Among 52,119 eligible participants who received antenatal corticosteroid treatment, the estimated incidence rates per 1000 person-years were 0.76 (95% confidence interval (CI): 0.69-0.83) for sepsis, 0.31 (95% CI: 0.27-0.36) for heart failure, and 11.57 (95% CI: 11.27-11.87) for gastrointestinal bleeding. The IRRs at 5 ~ 60 days after administration of antenatal corticosteroids were 5.91 (95% CI: 3.10-11.30) for sepsis and 4.45 (95% CI: 2.63-7.55) for heart failure, and 1.26 (95% CI: 1.02-1.55) for gastrointestinal bleeding; and the IRRs for days 61 ~ 180 were 2.00 (95% CI: 1.01-3.96) for sepsis, 3.65 (95% CI: 2.14-6.22) for heart failure, and 1.81 (95% CI: 1.56-2.10) for gastrointestinal bleeding. CONCLUSIONS: This nationwide population-based study suggests that a single course of antenatal corticosteroids is significantly associated with a 1.3- to 5.9-fold increased risk of sepsis, heart failure, and gastrointestinal bleeding in pregnant women. Maternal health considerations, including recommendations for adverse event monitoring, should be included in future guidelines for antenatal corticosteroid treatment.

Targeting histone deacetylase-3 blocked epithelial-mesenchymal plasticity and metastatic dissemination in gastric cancer.

BACKGROUND AND PURPOSE: Histone deacetylase (HDAC) inhibitors (HDIs) can modulate the epithelial-mesenchymal transition (EMT) progression and inhibit the migration and invasion of cancer cells. Emerging as a novel class of anti-cancer drugs, HDIs are attracted much attention in the field of drug discovery. This study aimed to discern the underlying mechanisms of Honokiol in preventing the metastatic dissemination of gastric cancer cells by inhibiting HDAC3 activity/expression. EXPERIMENTAL APPROACH: Clinical pathological analysis was performed to determine the relationship between HDAC3 and tumor progression. The effects of Honokiol on pharmacological characterization, functional, transcriptional activities, organelle structure changes, and molecular signaling were analyzed using binding assays, differential scanning calorimetry, luciferase reporter assay, HDAC3 activity, ER stress response element activity, transmission electron microscopy, immune-blotting, and Wnt/ß-catenin activity assays. The in vivo effects of Honokiol on peritoneal dissemination were determined by a mouse model and detected by PET/CT tomography. KEY RESULTS: HDAC3 over-expression was correlated with poor prognosis. Honokiol significantly abolished HDAC3 activity (Y298) via inhibition of NFκBp65/CEBPß signaling, which could be reversed by the over-expression of plasmids of NFκBp65/CEBPß. Treatments with 4-phenylbutyric acid (a chemical chaperone) and calpain-2 gene silencing inhibited Honokiol-inhibited NFκBp65/CEBPß activation. Honokiol increased ER stress markers and inhibited EMT-associated epithelial markers, but decreased Wnt/ß-catenin activity. Suppression of HDAC3 by both Honokiol and HDAC3 gene silencing decreased cell migration and invasion in vitro and metastasis in vivo. CONCLUSIONS AND IMPLICATIONS: Honokiol acts by suppressing HDAC3-mediated EMT and metastatic signaling. By prohibiting HDAC3, metastatic dissemination of gastric cancer may be blocked. Conceptual model showing the working hypothesis on the interaction among Honokiol, HDAC3, and ER stress in the peritoneal dissemination of gastric cancer. Honokiol targeting HDAC3 by ER stress cascade and mitigating the peritoneal spread of gastric cancer. Honokiol-induced ER stress-activated calpain activity targeted HDAC3 and blocked Tyr298 phosphorylation, subsequently blocked cooperating with EMT transcription factors and cancer progression. The present study provides evidence to demonstrate that HDAC3 is a positive regulator of EMT and metastatic growth of gastric cancer cells. The findings here imply that overexpressed HDAC3 is a potential therapeutic target for honokiol to reverse EMT and prevent gastric cancer migration, invasion, and metastatic dissemination. • Honokiol significantly abolished HDAC3 activity on catalytic tyrosine 298 residue site. In addition, Honokiol-induced ER stress markedly inhibited HDAC3 expression via inhibition of NFκBp65/CEBPß signaling. • HDAC3, which is a positive regulator of metastatic gastric cancer cell growth, can be significantly inhibited by Honokiol. • Opportunities for HDAC3 inhibition may be a potential therapeutic target for preventing gastric cancer metastatic dissemination.

[Analysis of a child with Verheij syndrome due to variant of PUF60 gene].

OBJECTIVE: To explore the clinical phenotype and genetic variant in a child with Verheij syndrome (VRJS). METHODS: A child who had presented at the Soochow University Affiliated Children's Hospital and Wujiang District Children's Hospital in July 2022 for "elevated scapula since early childhood" was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child had manifested elevated scapulae, torticollis, neck asymmetry, facial dysmorphism, dispersed café-au-lait spots, limited mobility of upper limbs and shoulder joints, and intellectual disability. Sequencing revealed that he has harbored a de novo heterozygous c.405dupT (p.Ile136Tyrfs*4) variant of the PUF60 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), this variant was classified as pathogenic (PVS1+PS2_moderate+PM2_supporting). Combined his clinical features and result of genetic testing, the child was diagnosed with VRJS due to variant of the PUF60 gene. CONCLUSION: The clinical manifestations of VRJS include facial dysmorphism, intellectual disability, elevated scapulae, vertebral fusion, other skeletal malformations, without significant abnormalities of the heart, kidney, and eyes, which need to be distinguished from Klippel-Feil syndrome. Above finding has expended the mutation spectrum of the PUF60 gene and provided a reference for delineation of the genotype-phenotype correlation of the VRJS.

Gene-set integrative analysis of multi-omics data using tensor-based association test.

MOTIVATION: Facilitated by technological advances and the decrease in costs, it is feasible to gather subject data from several omics platforms. Each platform assesses different molecular events, and the challenge lies in efficiently analyzing these data to discover novel disease genes or mechanisms. A common strategy is to regress the outcomes on all omics variables in a gene set. However, this approach suffers from problems associated with high-dimensional inference. RESULTS: We introduce a tensor-based framework for variable-wise inference in multi-omics analysis. By accounting for the matrix structure of an individual's multi-omics data, the proposed tensor methods incorporate the relationship among omics effects, reduce the number of parameters, and boost the modeling efficiency. We derive the variable-specific tensor test and enhance computational efficiency of tensor modeling. Using simulations and data applications on the Cancer Cell Line Encyclopedia (CCLE), we demonstrate our method performs favorably over baseline methods and will be useful for gaining biological insights in multi-omics analysis. AVAILABILITY AND IMPLEMENTATION: R function and instruction are available from the authors' website: https://www4.stat.ncsu.edu/~jytzeng/Software/TR.omics/TRinstruction.pdf. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex.

OBJECTIVE: Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear. Approach and Results: Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis. Nε-carboxymethyllysine (CML) and inflammatory cytokines levels in human sera and in several diabetic murine models were detected by ELISA, whereas liquid chromatography-tandem mass spectrometry analysis was used for whole eye tissues. The CML and p-Tpl2 expressions on the human retinal pigment epithelium (RPE) cells were determined by immunofluorescence. Intravitreal injection of pharmacological inhibitor or NA (neutralizing antibody) was used in a diabetic rat model. Retinal leukostasis, optical coherence tomography, and H&E staining were used to observe pathological features. Sera of diabetic retinopathy patients had significantly increased CML levels that positively correlated with diabetic retinopathy severity and foveal thickness. CML and p-Tpl2 expressions also significantly increased in the RPE of both T1DM and T2DM diabetes animal models. Mechanistic studies on RPE revealed that CML-induced Tpl2 activation and NADPH oxidase, and inflammasome complex activation were all effectively attenuated by Tpl2 inhibition. Tpl2 inhibition by NA also effectively reduced inflammatory/angiogenic factors, retinal leukostasis in streptozotocin-induced diabetic rats, and RPE secretion of inflammatory cytokines. The attenuated release of angiogenic factors led to inhibited vascular abnormalities in the diabetic animal model. CONCLUSIONS: The inhibition of Tpl2 can block the inflammasome signaling pathway in RPE and has potential clinical and therapeutic implications in diabetes-associated retinal microvascular dysfunction.

Quantitative assessment of normal hip cartilage in children under 9 years old by T2 mapping.

OBJECTIVE: To investigate the variation in T2 at different zones of normal hip cartilage in children and the relationship between T2 value and age. MATERIALS AND METHODS: Nineteen children with 30 normal hip joints were evaluated with a coronal T2 mapping sequence at a 3-Tesla MRI system. The femoral cartilage and acetabular cartilage were firstly segmented by mask-based interactive method and then equally divided into eight and six radial sections, respectively. Moreover, each radial section was further divided into two layers referring to the superficial and deep halves of the corresponding cartilage. Cartilage T2 of these sections and layers were measured and subsequently analyzed. RESULTS: There was a negative correlation between the T2 values in the hip cartilage and the age of children (rs < - 0.6, P1 < 0.05). Articular cartilage T2 increased at angles close to the magic angle (54.7°). Femoral cartilage and acetabular cartilage had a relatively shorter T2 in the radial sections near the vertex of the femoral head. The T2 values in superficial layers of both cartilages were significantly higher than those in deep layers (P < 0.05). CONCLUSION: The T2 value decreases as the cartilage developing into a more mature state. Cartilage T2 values in the weight-bearing areas are relatively low due to an increase of collagen density and the loss of interstitial water. The restriction of the water molecules by solid components in the deeper layer of cartilage may decrease the T2 values.

Cost-effectiveness evaluation of mammography screening program in Taiwan: Adjusting different distributions of age and calendar year for real world data.

BACKGROUND/PURPOSE: We estimated loss-of-life expectancy (LE) and lifetime medical expenditures (LME) stratified by stages to evaluate the cost-effectiveness of breast cancer (BC) screening in Taiwan. METHODS: We interlinked four national databases- Cancer Registry, Mortality Registry, National Health Insurance Claim, and Mammography Screening. A cohort of 123,221 BC was identified during 2002-2015 and followed until December 31, 2017. We estimated LE and loss-of-LE by rolling extrapolation algorithm using age-, sex-, and calendar-year-matched referents simulated from vital statistics. LME was estimated by multiplying monthly cost with survival probability and adjusted for annual discount rate. We calculated incremental cost-effectiveness ratio (ICER) by comparing the loss-of-LE of those detected by screening versus non-screening after accounting for administration fees and radiation-related excess BC. RESULTS: The LEs of stages I, II, III, and IV were 31.4, 27.2, 20.0, and 5.2 years, respectively, while the loss-of-LEs were 1.2, 4.9, 11.7, and 25.0 years with corresponding LMEs of US$ 73,791, 79,496, 89,962, and 66,981, respectively. The difference in LE between stages I and IV was 26.2 years while that of loss-of-LE was 23.8 years, which implies that a potential lead time bias may exist if diagnosis at younger ages for earlier stages were not adjusted for. The ICER of mammography seemed cost-saving after the coverage exceeded half a million. CONCLUSION: Mammography could detect BC early and be cost-saving after adjustment for different distributions of age and calendar year of diagnosis. Future studies exploring healthcare expenditure and impaired quality of life for false-positive cases are warranted.

Association Between Oral Corticosteroid Bursts and Severe Adverse Events : A Nationwide Population-Based Cohort Study.

BACKGROUND: Long-term use of oral corticosteroids has known adverse effects, but the risk from brief oral steroid bursts (≤14 days) is largely unknown. OBJECTIVE: To examine the associations between steroid bursts and severe adverse events, specifically gastrointestinal (GI) bleeding, sepsis, and heart failure. DESIGN: Self-controlled case series. SETTING: Entire National Health Insurance Research Database of medical claims records in Taiwan. PARTICIPANTS: Adults aged 20 to 64 years with continuous enrollment in the National Health Insurance program from 1 January 2013 to 31 December 2015. MEASUREMENTS: Incidence rates of severe adverse events in steroid burst users and non-steroid users, as well as incidence rate ratios (IRRs) for severe adverse events within 5 to 30 and 31 to 90 days after initiation of steroid therapy. RESULTS: Of 15 859 129 adult participants, 2 623 327 who received a single steroid burst were included. The most common indications were skin disorders and respiratory tract infections. The incidence rates per 1000 person-years in steroid bursts were 27.1 (95% CI, 26.7 to 27.5) for GI bleeding, 1.5 (CI, 1.4 to 1.6) for sepsis, and 1.3 (CI, 1.2 to 1.4) for heart failure. Rates of GI bleeding (IRR, 1.80 [CI, 1.75 to 1.84]), sepsis (IRR, 1.99 [CI, 1.70 to 2.32]), and heart failure (IRR, 2.37 [CI, 2.13 to 2.63]) significantly increased within 5 to 30 days after steroid therapy initiation and attenuated during the subsequent 31 to 90 days. LIMITATION: Persons younger than 20 years or older than 64 years were not included. CONCLUSION: Oral corticosteroid bursts are frequently prescribed in the general adult population in Taiwan. The highest rates of GI bleeding, sepsis, and heart failure occurred within the first month after initiation of steroid therapy. PRIMARY FUNDING SOURCE: National Health Research Institutes, Ministry of Science and Technology of Taiwan, Chang Gung Medical Foundation, and Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Reappraisal learning curve of laparoscopic Roux-en Y gastric bypass: retrospective results of one hundred and eight cases from a low-volume unit.

BACKGROUND: This study aimed to reevaluate the learning curve of laparoscopic Roux-en Y gastric bypass (LRYGB) in the modern era while considering a single surgeon's experience. METHODS: From the beginning of our LRYGB practice, all patients who met the regional criteria and underwent primary LRYGB were retrospectively enrolled. Patients with a body mass index (BMI) > 50 kg/m2 were excluded. Those who underwent surgery in 2016-17, 2018 and 2019 by a single surgeon with 10 + years of laparoscopic experience were assigned to groups A, B and C, respectively. The patient demographics and 30-day outcome data, including the operation time, length of stay (LOS), emergency room visits, readmission, and reoperation, were compared among the groups. RESULTS: One hundred and eight patients met the inclusion criteria; 36, 38, and 34 patients were assigned to groups A, B and C, respectively. There were no differences in age, sex distribution or common comorbidities among the groups; however, B had a lower BMI (35.1 kg/m2 vs. 37.0 kg/m2) and a higher rate of hypertension (44.7% vs. 22.2%) than group A. The operation time was markedly reduced (96.1 min and 114.9 min, p < 0.001), and the LOS was shortened (2.2 days and 2.9 days, p < 0.001) in group B compared to group A and remained stationary in group C, with no further reduction in 30-day complications. CONCLUSION: The learning process of LRYGB can be shortened to approximately 30 cases if conducted selectively by experienced laparoscopic surgeons. Further follow-up is required to verify the long-term safety and applicability in other patient subgroups.

Identifying individual risk rare variants using protein structure guided local tests (POINT).

Rare variants are of increasing interest to genetic association studies because of their etiological contributions to human complex diseases. Due to the rarity of the mutant events, rare variants are routinely analyzed on an aggregate level. While aggregation analyses improve the detection of global-level signal, they are not able to pinpoint causal variants within a variant set. To perform inference on a localized level, additional information, e.g., biological annotation, is often needed to boost the information content of a rare variant. Following the observation that important variants are likely to cluster together on functional domains, we propose a protein structure guided local test (POINT) to provide variant-specific association information using structure-guided aggregation of signal. Constructed under a kernel machine framework, POINT performs local association testing by borrowing information from neighboring variants in the 3-dimensional protein space in a data-adaptive fashion. Besides merely providing a list of promising variants, POINT assigns each variant a p-value to permit variant ranking and prioritization. We assess the selection performance of POINT using simulations and illustrate how it can be used to prioritize individual rare variants in PCSK9, ANGPTL4 and CETP in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) clinical trial data.

Health inequality: a longitudinal study on geographic variations in lung cancer incidence and mortality in Taiwan.

BACKGROUND: This study is aimed toward an analysis of the variations in lung cancer incidence and mortality, adjusted by population factors (age, gender, and year), between administrative areas. METHODS: This is a retrospective study, using 2005-2014 data in each administrative area from the Taiwan Cancer Registry database organized by the Health Promotion Administration. The yearly age-standardized (overall) and crude (stratified by gender and age) incidence/mortality (and their growth rates) for each administrative area were collected and calculated. We used a mixed model to analyze the repeated measurements of yearly incidence and mortality rates and used general linear regression to analyze their growth rates. RESULTS: It was found that male and elderly populations had significantly higher lung cancer incidence and mortality in Taiwan. After adjusting for gender, age, and calendar year, there were no significant variations in incidence among the administrative areas, while the mortality in Yilan County was significantly higher than that in Taipei City (the capital city of Taiwan). On the other hand, the incidence in the female and younger population and mortality growth rates were higher. The incidence growth rate in Keelung City was significantly lower than that in Taipei City, while there were no significant variations in mortality growth rate among administrative areas. CONCLUSIONS: This study found an inequality in the lung cancer burden among cities in Taiwan, which can serve as the basis for future resource allocations for lung cancer prevention and treatment in Taiwan.

Risk factors associated with renal crescentic formation in pediatric Henoch-Schönlein purpura nephritis: a retrospective cohort study.

BACKGROUND: The long-term prognosis of Henoch-Schönlein purpura (HSP) depends on the severity of renal involvement, and crescent formation is considered an important risk factor for poor prognosis of Henoch-Schönlein purpura nephritis (HSPN). The objective of this study was to evaluate factors affecting crescent formation in children with HSPN. METHODS: Demographic factors, clinical characteristics, and laboratory data of children with HSPN with or without crescents were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the risk factors of crescent formation in HSPN. RESULTS: A total of 191 children with HSPN were enrolled in the study. There were 107 (56%) males and 84 (44%) females, with a median age of 7 years (range: 2 years-15 years). International Study of Kidney Disease in Children (ISKDC) grading was used to divide subjects into two groups: those without glomerular crescent formation (ISKDC grades I-II, n = 146 cases) and those with glomerular crescent formation (ISKDC grades III-V, n = 45 cases). Logistic regression analysis showed that higher urinary white blood cell (WBC) count (OR = 3.300; 95% CI, 1.119-9.739; P = 0.0306) and higher urinary microalbumin/creatinine ratio (ACR) (OR = 25.053; 95% CI, 1.354-463.708; P = 0.0305) were independent risk factors for the formation of crescents in HSPN. The area under the receiver operating characteristic curve of urinary WBC and ACR were 0.753 and 0.698 respectively, with the Hosmer and Lemeshow goodness-of-fit test (P = 0.0669, P > 0.05). CONCLUSION: These results suggest that higher urinary WBC count and ACR should be strictly monitored for children with HSPN. Adequate clinical intervention for these risk factors may limit or prevent renal crescent formation.

Assessment of irreducible aspects in developmental hip dysplasia by magnetic resonance imaging.

BACKGROUND: The developmental dysplasia of the hip (DDH) can cause a wide range of pathological changes, and often requires surgical treatment. Preoperative evaluation is very important for DDH. We aimed to assess the diagnostic capability of magnetic resonance imaging (MRI) for irreducible aspects preventing hip reduction in DDH. METHODS: A total of 39 pediatric patients who received DDH evaluation in pediatric orthopedics from January 2015 to December 2019 were included. The samples included 4 cases of bilateral DDH and 35 cases of unilateral DDH, a total of 43 hip joint samples. All patients underwent surgical treatment, pathological examination and MRI of hip joint. RESULTS: With pathological results or intraoperative findings as the gold standard, the sensitivity and specificity of MRI were 90.3% and 83.3% for the affected labrum, 92% and 83.3% for thickening of the round ligament, 90.0% and 91.3% for atrophy of the iliopsoas muscle, and 100% and 100% for fibrofatty pulvinar tissue and joint effusion, respectively. CONCLUTIONS: The MRI showed an extraordinary capability of detecting these irreducible factors and helped surgeon choose the appropriate treatment strategies.

Nanoscale Surface Properties of Organic Matter and Clay Minerals in Shale.

Surface properties of shale play an essential role in adsorption, transport, and production of hydrocarbons from shale reservoirs. Nanoscale surface properties of kerogen and minerals of shale were examined by a series of techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIRS), and atomic force microscopy (AFM). The results show that aluminosilicate is the main component of inorganic matter, while kerogen chiefly consists of carbon. FTIRS and XPS analysis indicate that the chemical bonds of the kerogen surface are O-H, C-C, C-O, pyrrolic, and so on. In contrast to kerogen, illite's bonds are mainly Si-O and Al-O. AFM results indicate that the adhesion force of kerogen is higher than that of illite in shale. In addition, at a preloading force of 2500 nN, the adhesion force of kerogen increases from 40.8 to 118.2 nN when retraction velocity increases from 500 to 2500 nm/s. The adhesion forces of montmorillonite, calcite, and muscovite are 33.7 ± 6.28, 23.8 ± 11.8, and 105.1 ± 9.1 nN, respectively. The chemical composition and bonds have a profound effect on the adhesion force of shale, which further reveals the transport and adsorption mechanism of methane in kerogen.

Enhanced Adhesion of Carbon Nanotubes by Dopamine Modification.

According to the fact that gecko-inspired vertically aligned carbon nanotubes (VA-CNTs) exhibit ultrastrong adhesion, dopamine is utilized to make a modification to this traditional biomimetic material. The composite material is tested for adhesion performance under different environmental conditions by an atomic force microscope. The adhesion force of the modified VA-CNTs does not show obvious fluctuation during the gradual heating process; however, the material gains improved adhesion when increasing the ambient humidity. In addition, the modified CNTs show a stronger adhesion force than the original CNTs in their performance tests. The dopamine polymer has a good combination with CNTs, which is responsible for the aforementioned excellent performance. Overall, this modification method is simple, convenient, efficient, and environmentally friendly, which all indicates a promising future in its application. The modified CNTs are expected to be used for super-adhesion in harsh environments, as well as in the field of microelectronics.

Predictors of caregiver burden and care costs for older persons with dementia in Taiwan.

ABSTRACTObjectives:As a degenerative disease, the progression of dementia needs continued care provision and poses both psychological and financial burden for family caregivers of persons with dementia (PWD). This study seeks to compare predictors of care costs and caregiver burden, and to identify modifiable factors that could alleviate the burden faced by dementia caregivers. METHODS: This study interviewed 231 PWD-caregiver dyads in a dementia clinic at a teaching hospital in southern Taiwan in 2013. A follow-up study was conducted a year later, and 167 dyads completed the second interview. Data collected included PWD characteristics, caregiver characteristics, relationship to PWD, and social support to caregivers. Caregiver burden was measured with the Zarit Burden Interview instrument. The association between each predictor variable and cost of care and caregiver burden scores was examined using linear mixed models. RESULTS: Predictors of care costs were found to be different from predictors of caregiver burden: functional declines measured by Katz's activities of daily living (ADL) scale were associated with total cost as compared to behavioral disturbance measured by Neuropsychiatric Inventory (NPI), which showed no impact on care costs. However, NPI was a significant predictor of caregiver burden. Caregivers who were better-off financially also reported significantly lower caregiver burden. CONCLUSIONS: Since predictors of care costs were different from the predictors of caregiver burden, providing training to caregivers in addressing PWD's behavioral disturbance and proving financial assistance to low income caregivers could be effective in reducing caregiver burden.

Surface Properties of Organic Kerogen in Continental and Marine Shale.

The adhesion energy of kerogen in continental and marine shale was innovatively discovered using the colloid probe technique with atomic-force microscopy (AFM). AFM results indicated that the adhesion force of kerogen was higher than the inorganic material in both the continental and marine shale samples. The chemical elements in the two kinds of samples were measured by energy-dispersive X-ray analysis with scanning electron microscopy (SEM). The chemical compositions of kerogen involved C═C bonding, C═O bonding, pyridine nitrogen, and pyrrole nitrogen, whereas the primary constituent involving inorganic matter was Si-O bonding. These results were confirmed by Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The high percentages of C═C and C═O bonding in kerogen are attributed to the large dipole on the kerogen surface which allowed kerogen to contain liquid and gaseous hydrocarbons.

Simultaneous segmentation and bias field estimation using local fitted images.

Level set methods often suffer from boundary leakage and inadequate segmentation when used to segment images with inhomogeneous intensities. To handle this issue, a novel region-based level set method was developed, in which two different local fitted images are used to construct a hybrid region intensity fitting energy functional. This novel method enables simultaneous segmentation of the regions of interest and estimation of the bias fields from inhomogeneous images. Our experiments on both synthetic images and a publicly available dataset demonstrate the feasibility and reliability of the proposed method.

Geographic Variations and Time Trends in Cancer Treatments in Taiwan.

BACKGROUND: Targeted therapies have become important treatment options for cancer care in many countries. This study aimed to examine recent trends in utilization of antineoplastic drugs, particularly the use of targeted therapies for treatment of cancer, by geographic region in Taiwan (northern, midwestern, southern, and eastern regions and the outer islands). METHODS: This was a retrospective observational study of antineoplastic agents using 2009-2012 quarterly claims data from Taiwan's National Health Insurance Research Database. Yearly market shares by prescription volume and costs for targeted therapies among total antineoplastic agents by region were estimated. We used multivariate regression model and ANOVA to examine variations in utilization of targeted therapies between geographic regions and used ARIMA models to estimate longitudinal trends. RESULTS: Population-adjusted use and costs of antineoplastic drugs (including targeted therapies) were highest in the southern region of Taiwan and lowest in the outer islands. We found a 4-fold difference in use of antineoplastic drugs and a 49-fold difference in use of targeted therapies between regions if the outer islands were included. There were minimal differences in use of antineoplastic drugs between other regions with about a 2-fold difference in use of targeted therapies. Without considering the outer islands, the market share by prescription volume and costs of targeted therapies increased almost 2-fold (1.84-1.90) and 1.5-fold (1.26-1.61) respectively between 2009 and 2012. Furthermore, region was not significantly associated with use of antineoplastic agents or use of targeted therapies after adjusting for confounders. Region was associated with costs of antineoplastic agents but it was not associated with costs of targeted therapies after confounding adjustments. CONCLUSIONS: Use of antineoplastic drugs overall and use of targeted therapies for treatment of cancer varied somewhat between regions in Taiwan; use was notably low in the outer islands. Strategies might be needed to ensure access to cancer care in each region as economic burden of cancer care increase due to growing use of targeted therapies.

Trends in diagnostic approaches for pediatric appendicitis: nationwide population-based study.

BACKGROUND: To define the benefits of different methods for diagnosis of pediatric appendicitis in Taiwan, a nationwide cohort study was used for analysis. METHODS: We identified 44,529 patients under 18 years old who had been hospitalized with a diagnosis of acute appendicitis between 2003 and 2012. We analyzed the percentages of cases in which ultrasound (US) and/or computed tomography (CT) were performed and non-perforated and perforated appendicitis were diagnosed for each year. Multivariate logistic regression analyses were performed to evaluate risk factors for perforated appendicitis. RESULTS: There were more cases of non-perforated appendicitis (N = 32,491) than perforated appendicitis (N = 12,038). The rate of non-perforated cases decreased from 0.068% in 2003 to 0.049% in 2012; perforated cases remained relatively stable at 0.024%~0.023% from 2003 to 2012. The percentage of CT evaluation increased from 3% in 2003 to 20% in 2012; the rates of US or both US and CT evaluations were similar annually. The percentage of neither CT nor US evaluation gradually decreased from 97% in 2003, to 79% in 2012. The odds ratios of a perforated appendix for those patients diagnosed by US, CT, or both US and CT were 1.227 (95% confidence interval (CI) 0.91, 1.65; p = 0.173), 2.744 (95% CI 2.55, 2.95; p < 0.001), and 5.062 (95% CI = 3.14, 8.17; p < 0.001), respectively, compared to patients who did not receive US or CT. The odd ratios of a perforated appendix for those patients 7-12 and ≤6 years old were 1.756 (95% CI 1.67, 1.84; p < 0.001) and 3.094 (95% CI 2.87, 3.34; p < 0.001), respectively, compared to those 13-18 years old. CONCLUSIONS: Our study demonstrated that using CT scan as a diagnostic tool for acute appendicitis increased annually; most patients especially those ≤6 years old who received CT evaluation had a greater risk of having perforated appendicitis. We recommend a prompt appendectomy in those pediatric patients with typical clinical symptoms and physical findings for non-complicated appendicitis to avoid the risk of appendiceal perforation.