Miracle-dz/UniFAR-FTUs huggingface dataset:
Interobserver Variation in the Histopathologic Reporting of Key Prognostic Parameters, Particularly Clark Level, Affects Pathologic Staging of Primary Cutaneous Melanoma

Background:Accurate reporting of prognostically important histopathologic parameters is critical for optimal management of melanoma patients. Previous studies have shown that assessment of Breslow thickness and ulceration is more reproducible between pathologists than estimation of Clark level. However, detailed quantification of the magnitude of variation between observers and its effect on melanoma staging has not been reported. Methods:Nine hundred twelve melanoma patients referred to the Sydney Melanoma Unit (SMU) with pathology reports from referring pathology services and reports following histopathologic review by SMU pathologists were studied. Breslow thickness, Clark level, ulceration, and pathologic staging (American Joint Committee on Cancer, 2002) data were extracted from each matched pair of SMU and non-SMU reports. The degree of concordance for these parameters was assessed. Results:There was excellent agreement between SMU and non-SMU pathologists in the assessment of Breslow thickness (&kgr; = 0.883; intraclass correlation coefficient = 0.968) and ulceration (&kgr; = 0.832), while that for Clark level was only moderate (&kgr; = 0.627). The degree of concordance in the assessment of overall pathologic stage was excellent (96.2%), but there was poor agreement for the evaluation of substages IB (77.3%) and IIB (72.4%), due largely to poor Clark level concordance. Conclusions:Although there was a high level of agreement between pathologists in the assessment of overall pathologic stage, the significant level of discordance in pathologic substaging suggests that accurate and reliable substage-based prognostic prediction may not be possible in all cases. It will be important to consider these issues in future revisions of the American Joint Committee on Cancer melanoma staging system.
Dual-Biomarker Imaging of Regional Cerebral Amyloid Load and Neuronal Activity in Dementia with PET and 11C-Labeled Pittsburgh Compound B

PET studies with biomarkers of regional neuronal activity (cerebral glucose metabolism or blood flow [CBF]) and amyloid-β (Aβ) depositions provide complementary information for the early diagnosis of dementia and follow-up of patients with dementia. We investigated the validity of relative regional CBF estimates (R1) gained from pharmacokinetic analyses of 11C-labeled Pittsburgh compound B (11C-PIB) PET studies as a marker of neuronal activity and neurodegeneration. Methods: Twenty-two patients with cognitive impairment (16 patients with early Alzheimer disease) underwent 18F-FDG and 11C-PIB PET studies for the assessment of regional glucose metabolism and Aβ load. Parametric images of R1 (relative CBF) and binding potential (BPND; Aβ load) were generated by 2-step simplified reference tissue model (SRTM2) analyses of dynamic 11C-PIB data. Volume-of-interest and voxel-based statistical analyses were performed to investigate the association between normalized 18F-FDG uptake and 11C-PIB R1 and the correlation of these measures with symptom severity (Mini-Mental State Examination [MMSE] scores) in patients with Alzheimer disease. Results: SRTM2 analyses provided high-quality 11C-PIB R1 images that were comparable to 18F-FDG PET images. Regional 11C-PIB R1 values strongly correlated with normalized regional 18F-FDG uptake when correlations were calculated separately for each patient (R2 [mean ± SD], 0.73 ± 0.11) or across all regions of all patients (R2, 0.62). A regression model including 18F-FDG uptake, subject identification, and region grouping (into cortical, subcortical, and limbic regions to allow for possible differences in flow/metabolism coupling) accounted for 86% of total 11C-PIB R1 variability. Voxel-based correlation analyses of 18F-FDG uptake and 11C-PIB R1 with MMSE scores revealed similar core findings of positive correlations in the posterior cingulate gyrus/precuneus and negative correlations (preserved activity) in the bilateral sensorimotor cortex. There was no correlation between Aβ load (BPND) and MMSE scores. Conclusion: These results strongly suggest that 11C-PIB R1 can serve as a complementary biomarker of neuronal activity and, thus, neurodegeneration in addition to Aβ load given by 11C-PIB BPND. Further studies are needed to validate the diagnostic value of dual-biomarker 11C-PIB PET studies in comparison with combined 18F-FDG and 11C-PIB PET studies. Compared with the latter, dual-biomarker 11C-PIB PET greatly reduces costs and burden for patients.
Neural Interaction Between Risk Sensitivity and Cognitive Control Predicting Health Risk Behaviors Among Late Adolescents

The developmental period of adolescence is characterized by increasing incidence of health risk behaviors (HRBs). Based on theoretical models that emphasize the moderating role of cognitive control, this study examined how neural correlates of cognitive control and risk sensitivity interact to predict HRBs among late adolescents (17-20 years). Neuroimaging data indicate that risk-related hemodynamic activity in the anterior insula during anticipation of uncertain outcomes predicts HRBs among late adolescents exhibiting greater dorsal anterior cingulate cortex (dACC) activity during a cognitive interference task but not among late adolescents requiring less dACC activity. These results present neural evidence for a significant moderating effect of cognitive control on the link between risk sensitivity and HRBs among late adolescents.
The Great Recession and the Health of Young Children: A Fixed-Effects Analysis in Ireland

Economic recessions have been linked to adult health, but few studies have examined how recessions influence the health of young children. This study examined the impact of life transitions linked to the recent financial crisis on the health of young children in Ireland. Data came from the Growing Up in Ireland Infant Cohort Study (n = 11,134), which assessed children before (2008), during (2011), and after (2013) the Great Recession that followed the financial crisis of 2008 and incorporated questions on the impacts of the financial crisis on families. Using fixed-effects models to control for confounding, we found that a reduction in welfare benefits during the recession was associated with a significant increase in the risks of asthma (β = 0.014, 95% confidence interval (95% CI): 0.004, 0.023) and atopy (β = 0.014, 95% CI: 0.001, 0.027). While parental job loss was not associated with child health, a reduction in working hours was associated with increased reports of child health problems (β = 0.024, 95% CI: 0.004, 0.043), as were difficulties affording basic necessities (β = 0.019, 95% CI: 0.001, 0.038). Results suggest that failing to protect vulnerable families and children during economic recessions may have long-lasting implications for child health.
Current and future efforts toward the prevention of type 1 diabetes

Great strides have been made in our understanding of the natural history of ‘pre‐type 1’ diabetes as well as in the post diagnosis period. For now, an inability to successfully prevent the disease limits screening outside of the research setting. While studies of both humans with various levels of risk for type 1 diabetes as well as animal models for the disease have increased our understanding of the disorder, the development of a safe and effective therapeutic intervention capable of reversing or preventing type 1 diabetes remains elusive. Worldwide primary, secondary, and tertiary prevention studies have been undertaken and both past and current studies are extensively reviewed in this manuscript. Intervention studies in new‐onset and established type 1 diabetes patients have to date shown fairly limited success with most effects seen within the first 6–12 months post therapy. Long‐term outcome remains to be determined. Improved and innovative trial designs, more rapid testing of both antigen specific and combination therapies in different populations (at‐risk, new‐onset, and established type 1 diabetes), continuing to fill the mechanistic voids in the etiopathogenesis of type 1 diabetes, and the development of validated biomarkers will hasten efforts toward reversing and preventing the disease. For successful prevention, therapy must be safe and must target not only effective control of the autoimmune process culminating in type 1 diabetes but also protection or replacement of lost β‐cell function.
Efficacy of liquid-based cytology versus conventional smears in FNA samples

Background: Liquid-based cytology (LBC) is fast becoming a useful method in evaluating both gynecological and non-gynecological preparations, including fine needle aspiration (FNA) cytology. Even distribution of cells, decreasing obscuring background elements like blood and mucus, well preserved nuclear and cytoplasmic details and rapid fixation helps in better visualization of cells. Aim: This study was conducted to asses the diagnostic accuracy of liquid–based cytology versus conventional smears in fine needle aspiration samples. Study Design: In this prospective study, we had 110 cases, including 30 cases of breast, 40 of lymph node, 10 of salivary glands, 18 of thyroid and 12 of bone and soft tissue. In each case, two passes were performed. The first pass was for conventional preparation (CP) and the second pass yielded material for thin-prep (TP) preparation. Both CP and TP smears were compared for cellularity, background blood and necrotic cell debris, cell architecture, informative background, presence of a monolayer of cells and nuclear and cytoplasmic details by a semiquantitative scoring system. Wilcoxon's signed rank test on an SPSS program was used for statistical analysis. Results: Diagnostic accuracy was better in LBC smears compared with CP smears due to lack of background debris and better cell morphology, which was performed according to Wilcoxon's signed rank test, yielding a P-value of <0.001. However, in some cases, because of a decrease in cell size, clustering and altered background in LBC, a support of CP was essential. Conclusion: LBC performed on FNA samples can be a simple and valuable technique. Only in few selected cases, where background factor is an essential diagnostic clue, a combination of both CP and TP is necessary.
Comparison of the Effect of Combination Therapy with an Angiotensin II Receptor Blocker and Either a Low-Dose Diuretic or Calcium Channel Blocker on Cardiac Hypertrophy in Patients with Hypertension

Left ventricular hypertrophy (LVH) regression is an important issue in hypertensive patients. Patients with LVH who had received the angiotensin receptor blocker (ARB) treatment for 8 weeks and had not reached the target blood pressure level were enrolled in the study. Patients were assigned to either losartan (50 mg)/hydrochlorothiazide (HCTZ, 12.5 mg) group or ARB + CCB group (usual dose of ARB and calcium channel blocker, CCB). After 48 weeks, LV mass index was found to be reduced significantly in the losartan/HCTZ group but not in the ARB + CCB group. These results suggest that combination therapy of an ARB and diuretic has greater potential to cause regression compared with an ARB and CCB.
PENGARUH PROFITABILITAS, STRUKTUR ASET, PERTUMBUHAN PENJUALAN DAN UKURAN PERUSAHAAN TERHADAP STRUKTUR MODAL PERUSAHAAN MANUFAKTUR DI BURSA EFEK INDONESIA

The capital struktur modal is a balance between the use of equity capital with the use of debt, which means how much equity and how much debt will be used, so as to generat optimal capital structure. This study aims to examine the effect of propability, aset struktur, sales growth and size of the company’s capital srtuktur on manufacturing companies Listed in Indonesia Stock Exchange (BEI) in the year 2012-2014. The data used is data companies Listed on the Stock Exchange in the period 2012-2014. Researchers using purposive sampling and obtained a sample of 181 observation data. Analysis of data using multiple linier regression testing. The results showed that :Profitability negatif effect on the capital structure, asset structure does not effect the company’s capital structure, sales growth did not effect the company’s capital structure, the size of the company and significant positif effect on the company’s capital strukture Keywords : profitability, asset structure, sales groth, firm size and capital structure
A simple and sensitive HPLC method for analysis of imipramine in human plasma with UV detection and liquid-liquid extraction: Application in bioequivalence studies

High-performance liquid chromatography (HPLC) methods employing ultraviolet (UV) detector are not sufficiently sensitive to measure the low plasma concentrations following single oral dose of imipramine. Therefore, in the present study a simple, rapid and yet sensitive HPLC method with UV detection was developed and validated for quantitation of imipramine in human plasma samples. An efficient liquid-liquid extraction (LLE) of imipramine from plasma with the mixture of hexane/isoamyl alcohol (98:2) and back extraction of the drug in acidic medium concomitant with evaporation of organic phase allowed the use of UV detector to conveniently measure plasma levels of this compound as low level as 3 ng/ml. Separation was achieved on a μ-Bondapak C18 HPLC column using sodium hydrogen phosphate solution (0.01 M)/acetonitrile (60/40 v/v) at pH 3.5 ± 0.1 at 1.5 ml/min. Trimipramine was used as the internal standard for analysis of plasma samples. The retention times for imipramine and trimipramine were 4.3 and 5.2 min, respectively. Calibration curve was linear in the range of 3-40 ng/ml using human plasma with the average extraction recovery of 85 ± 5%. Imipramine was found to be stable in plasma samples with no evidence of degradation during three freeze-thaw cycles and three months storage at -70°C. The current validated method was finally applied in bioequivalence studies of two different imipramine products according to a standard two-way crossover design with a two weeks washout period.
Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists

Although adipose‐derived stem cells (ASCs) are an attractive cell source for bone tissue engineering, direct use of ASCs alone has had limited success in the treatment of large bone defects. Although bone morphogenetic proteins (BMPs) are believed to be the most potent osteoinductive factors to promote osteogenic differentiation of ASCs, their clinical applications require supraphysiological dosage, leading to high medical burden and adverse side effects. In the present study, we demonstrated an alternative approach that can effectively complement the BMP activity to maximize the osteogenesis of ASCs without exogenous application of BMPs by regulating levels of antagonists and agonists to BMP signaling. Treatment of ASCs with the amiloride derivative phenamil, a positive regulator of BMP signaling, combined with gene manipulation to suppress the BMP antagonist noggin, significantly enhanced osteogenic differentiation of ASCs through increased BMP–Smad signaling in vitro. Furthermore, the combination approach of noggin suppression and phenamil stimulation enhanced the BMP signaling and bone repair in a mouse calvarial defect model by adding noggin knockdown ASCs to apatite‐coated poly(lactic‐coglycolic acid) scaffolds loaded with phenamil. These results suggest novel complementary osteoinductive strategies that could maximize activity of the BMP pathway in ASC bone repair while reducing potential adverse effects of current BMP‐based therapeutics.
Medical investigations requested by patients: how do primary care physicians react?

BACKGROUND AND OBJECTIVES We investigated the characteristics of patients who request medical investigations and the type of tests requested to study the manner in which primary care physicians react to these requests. METHODS The study was conducted within the framework of a national health insurance system. Twelve primary care practices from three randomly chosen clinics with different population characteristics participated in the study. The attending physicians were instructed to ask all patients who presented to the clinics within a 7-month period and requested a medical test to complete a questionnaire, indicating the type of test(s) requested and the reason. The physicians were asked to rate the manner in which the patient made the request, their own reaction to the request, and whether they ordered the tests that were requested. RESULTS During the survey period, 12,322 patients visited the clinics, of whom 295 (2.4%) were reported by a physician to have requested a medical investigation. More-educated patients were more likely to request tests for disease prevention. The types of tests requested were imaging scans, laboratory (blood) tests, and others. The main reason for the request was symptoms (60%), followed by disease prevention (25%). More than 30% of the requests generated self-reported negative feelings in the physician. Physician compliance with patient requests was not significantly correlated with the reason for the request. Laboratory tests were ordered significantly more often than other types. There was a strong correlation between physicians' compliance with the request and physicians' feelings about the request. CONCLUSION Our findings raise questions about the frequency with which physicians order tests solely in response to patients' requests and provide information about circumstances in which patients make requests for medical investigations.
Interconnectedness in the Financial Sector: Three Essays on the Impact of the Financial Crisis and Banking Shocks on Insurance Firms

This thesis consists of three essays on the interconnectedness between banks and insurance firms. The aim is to answer two important research questions: First, what is the impact of shocks from the banking sector, and the financial crisis of 2008 in particular, on the stock prices of insurance firms and the competitive environment in the insurance sector? Second, do regulatory authorities have the means to mitigate such crises, that is, does the regulatory framework to predict and counteract financial distress in the insurance sector work adequately during a severe financial crisis? The first essay analyzes the consequences of the financial crisis of 2008 on the competitive situation in the German insurance sector. In addition, it examines whether insurance groups’ strategic group affiliation can affect the performance of their subsidiaries. The second essay questions how reliably regulators can forecast the financial strength of insurance firms during the financial crisis of 2008. The third essay examines the impact of policy interventions during the crisis on the stock prices of U.S. insurance firms. In addition, it analyzes the stock market response of insurers towards various shocks from the banking sector.
Analysing and aggregating visitor tracks in a protected area

The advent of location-based technologies deployed in protected areas provides both visitors and managers of such areas with new opportunities. In this paper we investigate the potential for mining individual tracks of visitors’ geospatial lifelines to both extract information describing aggregated patterns of group behaviour and characterise individual actions. Methods to spatio-temporally cluster individual behaviour and identify potential locations for specific actions (e.g. do visitors stop here to look at wildlife), whilst handling uncertainty in location, are described and applied to test the hypotheses that firstly, visitor behaviour is altered by the provision of information, and secondly whether the mode of information provision (e.g. in the form of a paper map or though an location-based service) influences visitor behaviour. The results of experiments with 140 visitors to a nature trail on the island of Texel in the Netherlands show statistically significant differences in time spent at locations where information was “pushed” to the visitors.
Culture vs. Bias: Can Social Trust Mitigate the Disposition Effect?

We examine whether the investors sensitivity to behavioral biases is influenced by the social norms they are exposed to. We focus on the disposition effect of mutual fund investors. We consider two competing hypotheses. On the one hand, trust, by increasing the credibility of the numbers reported by the fund managers elicits stronger investor reactions. This results in a higher flow-performance sensitivity, which mitigates the tendency of selling winners and holding onto losers. One the other hand, societal trust, reducing the concern of expropriation, lowers the necessity for investors to react to bad performance. The resulting lower flow-performance sensitivity increases the disposition effect. Based on a proprietary dataset of the complete account-level trading information for all investors of a mutual fund family in China, we find compelling evidence that: 1) fund investors exhibit disposition effect; 2) a higher degree of social trust is associated with higher flow-performance-sensitivity; 3) (high) trust-induced flows mitigate the disposition effect. Our results suggest that behavioral bias may be strongly influenced by social norms.
Religious Workers' Density and the Racial Earnings Gap

We explore differences between Black and White Non-Hispanic workers in the relationship between childhood exposure to religious workers and a worker's labor market outcomes thirty years later. We identify this relationship by exploiting two sources of variation: we use changes in the number of religious workers within states, and we use states' differences by following workers who moved to a different state. Our results suggest that a one percent increase in the number of clergy increases the earnings of Black workers by a range from 0.027 to 0.082 percent relative to the increase in the earnings of White workers.
Corporate Online Reporting and Their Determinants in Indian Services Sector

The study examines the status of corporate online reporting in the Indian services sector. It also explores the pattern and determinants affecting corporate online reporting. The paper uses content analysis for investigating the level and extent of corporate online reporting. A corporate online reporting index has been developed for the study, dividing the frame into three major headings namely, general, financial and presentation indexes. OLS regression is used for checking the determinants affecting corporate online disclosure. The study yields three major findings. First, results reveal that corporate online reporting measured by the three different indexes has a significant relationship with the size of the hotel. Second, there is negative and significant association between certain key determinants such as productivity, shareholders profitability and liquidity of the companies. Finally, other determinants such as profitability, leverage and growth are not significantly associated with corporate online reporting of the Indian service sector firms. The paper is built around the concept of transparency and reporting on the web that may facilitate the investors and stakeholders. The result is a novel approach to discuss corporate online reporting and transparency that contributes to other critical voices concerned about the value and effects of corporate online reporting.