Miracle-dz/UniFAR-FTUs huggingface dataset:
Time-to-Treatment Failure As the Primary End Point of a First-Line Advanced Gastric Cancer Randomized Trial: How Confused Would You Want Us to Be?

TO THE EDITOR: We read the report by Guimbaud et al 1 with interestandappreciatetheirenormousefforttoconductthistrial.We, however, remain concerned regarding the study design, chosen primary end point, the two regimens investigated, and finally, the conclusions drawn. In general, both regimens performed poorly (the median duration of therapy was only 4 months) compared with previouslyreportedregimensdocetaxel,cisplatin,andfluorouacil;cisplatin andfluorouacil; or S1/cisplatin. 2,3 The overall grade 3 or 4 toxicity rate was unacceptably high (84% for epirubicin, cisplatin, and fluorouracil [ECF] and 69% for fluorouracil, leucovorin, and irinotecan [FOLFIRI]). Treatment-relatedmortalityofapproximately4%isalso high and not acceptable. Based on these results, one could argue that none of these two regimens should be recommended to our patients with advanced gastric cancer in the first-line setting. Contribution of epirubicin to prolongation of overall survival (OS) has never been documented and similarly, irinotecan never produced prolongation
Human equilibrative nucleoside transporter 1 levels predict response to gemcitabine in patients with pancreatic cancer.

BACKGROUND & AIMS The human equilibrative nucleoside transporter (hENT1) protein transports gemcitabine into cells. Small retrospective studies in pancreatic cancer suggest that levels of hENT1 protein or messenger RNA may have prognostic value. We studied the predictive value of hENT1 levels in a cohort of pancreatic adenocarcinoma patients from the large prospective randomized adjuvant treatment trial RTOG9704. METHODS In RTOG9704, 538 patients were assigned randomly, after surgical resection, to groups that were given either gemcitabine or 5-fluorouracil (5-FU). Immunohistochemistry for hENT1 was performed on a tissue microarray of 229 resected pancreatic tumors from RTOG9704 and scored as having no staining, low staining, or high staining. Associations between hENT1 protein and treatment outcome were analyzed by unconditional logistic regression analysis using the chi-square test and the Cox proportional hazards model. RESULTS HENT1 expression was associated with overall and disease-free survival in a univariate (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.29-0.91; P= .02; and HR, 0.57; 95% CI, 0.32-1.00; P= .05) and multivariate model in the group given gemcitabine (HR, 0.40; 95% CI, 0.22-0.75; P= .004; and HR, 0.39; 95% CI, 0.21-0.73; P= .003). hENT1 expression was not associated with survival in the group given 5-FU. CONCLUSIONS In this prospective randomized trial, hENT1 protein expression was associated with increased overall survival and disease-free survival in pancreatic cancer patients who received gemcitabine, but not in those who received 5-FU. These findings are supported by preclinical data; the gemcitabine transporter hENT1 is therefore a molecular and mechanistically relevant predictive marker of benefit from gemcitabine in patients with resected pancreatic cancer.
Refining ancient carbon dioxide estimates: Significance of coccolithophore cell size for alkenone-based pCO2 records

[1] Long-term alkenone-based pCO2 records are widely applied in paleoclimate evaluations. These pCO2 estimates are based on records of the carbon isotope fractionation that occurs during marine haptophyte photosynthesis (ɛp37:2). In addition to the concentration of aqueous CO2 (CO2(aq)) the magnitude of ɛp37:2 is also influenced by algal growth rates and cell geometry. To date, the influence of haptophyte cell geometry on the expression of ancient ɛp37:2 values has received little attention. This study evaluates changes in cell geometry of ancient alkenone-producing algae at Deep See Drilling Project Site 516 in the southwest Atlantic Ocean by analyzing individual coccolith dimensions, which are proportional to algal cell volume and surface area. We show that during part of the early Miocene, mean cell sizes of alkenone-producing algae were smaller relative to modern Emiliania huxleyi. Cell size variations coincide with significant changes in ɛp37:2, with a distinct 6‰ decrease in ɛp37:2 at ∼20.3 Ma associated with a 27% increase in haptophyte cell sizes. These changes in cell size impact ɛp37:2-based interpretations of growth rate variation and CO2(aq) estimates for this southwest Atlantic site. After correcting for cell geometry, CO2(aq) estimates at Site 516 are consistent with those reported from other oligotrophic sites during this time, resulting in overall low atmospheric pCO2 estimates (<350 ppmv) for the early Miocene.
Phototransformation of the red-light-absorbing form of undegraded pea phytochrome by laser flash excitation.

The phototransformation of undegraded pea phytochrome, which was estimated to be about 30 to 40% pure, from its red-light-absorbing form to its far-red-light-absorbing form was examined at 2-4°C after laser flash excitation at 655 nm using a custom-designed multichannel transient spactra analyzer. A difference spectrum measured 10 μsec after the flash showed an absorbance increase at 692 nm, a decrease at 660 nm and a slight decrease at 604 nm. With time in darkness, the peak at 692 nm gradually decreased in magnitude and shifted to 695 nm. A decay curve of absorbance at 692 nm between 10 and 500 μsec after the flash could be resolved into two reaction components, one proceeding with a rate constant of 46,000 sec(-1) and the other with one of 2,500 sec(-1). The faster component has not been reported previously. Difference spectra also indicated that a small but significant increase in absorbance between 400 and 410 nm and decrease around 360 nm took place 10-260 μsec after the flash.
A study of the dynamics of imipramine accumulation in the isolated perfused rabbit lung.

An isolated perfused rabbit lung preparation (IPL) was used to study the uptake, accumulation, and efflux of the tricyclic amine imipramine (IMIP). The rate of IMIP uptake into the IPL was resolved into two exponential components (rates 1 and 2 of uptake). The initial velocities for these uptake components were linearly related to the concentration of IMIP in the perfusate (Cp). This linear relationship indicates that IMIP accumulated in the IPL by diffusion and/or binding. The steady-state accumulation of IMIP was obtained by integration of the exponential expression relating the rate of IMIP uptake to time. The amount of IMIP accumulated at steady state by rate 1 was linearly related to Cp, whereas the amount of IMIP accumulated at steady state by rate 2 was saturable with respect to Cp. These steady-state data are in agreement with the steady-state accumulation data previously reported from experiments with the recirculating blood-perfused rabbit lung. In the absence of IMIP in the perfusate. IMIP that had previously accumulated in the IPL effluxed from the lung at three rates (t1/2 = 18 sec, 58 sec, and 8.25 min), which indicates that accumulated IMIP was in at least three pools in the lung. In addition, a noneffluxable pool was detected which was not the result of irreversible binding to tissue.ated in pools 1 and 2 by rate 1 of uptake. The IMIP in pool 3 and in the noneffluxable pool was accumulated in the IPL by rate 2 of uptake. Efflux pool 3 and the IMIP accumulated at a steady state by rate 2 of uptake were resolved by a Hofstee plot into a biphasic curve indicating two types of binding sites. The noneffluxable pool of IMIP in the IPL was saturable with increasing Cp and represented approximately 30% of the IMIP accumulated by rate 2 into pool 3. Rate 2 of uptake, pool 3, and particularly the noneffluxable pool of IMIP in the IPL are possibly responsible for the accumulation and persistence of Imip in the lung as seen in whole body distribution studies. The physicochemical properties of IMIP and other compounds known to be accumulated in lung tissue are discussed in relation to the possible involvement of lung phospholipids and the compartmentalization of IMIP in the concentric lamellar organelles of the lung.
Abstract ID: A1586 SPIN-POLARIZATION IN FRACTIONAL QUANTUM HALL EFFECT

Experimental data show a number of plateaus of varying widths in the magnetic-field dependence of the electron-spin-polarization for fractional quantum Hall states. We have calculated the magnetic-field dependence of the spin-polarization using a new theory. We start by adopting the Landau gauge and ignoring Coulomb interactions between electrons; then we construct single electron states in equally spaced orbitals. For a number of filling factors we have examined the many-electron states with electron configurations having minimum classical Coulomb energy. The residual Coulomb interactions in each many-electron state produce spin-exchange-forces. We have solved the eigenvalue problem of the interaction Hamiltonian composed of nearest neighbor spin-exchange-interactions. From the eigenvalues we have calculated the magnetic-field dependence of the spin-polarization. Our results are in good accord with the magnetic-field dependence in experimental results, including the number and shape of the plateaus.
Estimation of photosynthesis and calcification rates of Corallina elongata Ellis and Solander, 1786, by measurements of dissolved oxygen, pH and total alkalinity*

Experiments were conducted on the calcareous red alga, Corallina elongata , a species representative of shallow water vegetal cover in Mediterranean areas with biomass ranging from 820 to 2544 gDW.m -2 , in order to estimate its productivity and calcification rates. Carbonate and oxygen budgets were estimated on samples incubated in situ under natural light cycles, by measuring initial and final dissolved oxygen, pH and alkalinity levels. In light conditions, oxygen concentrations and pH values increased as a consequence of oxygen production and carbon dioxide consumption due to the productivity process, and were a direct function of sample biomass. Strictly-reverse dynamics were recorded in dark conditions. A comparison of photosynthetic performances was conducted on a non-calcareous green alga, Ulva rigida , which showed higher rates of oxygen production and pH modification than C. elongata , but no significant change in total alkalinity. For C. elongata , a significant decrease in total alkalinity with incubation time was observed under light conditions, which was directly related to the algal sample biomass (R 2 = 0.95; n=16). Light to dark calcification ratio (L/D) was about 3.6. In these experiments, the photosynthetic quotient of C. elongata was 0.89, its net carbon productivity was 2.5 g C.m -2 . d -1 , gross production to daily respiration (Pg/R) was about 4.9 and its calcification rate was estimated at 13.8 g CaCO 3 . m -2 . d -1 .
Test-Driven Development as an Innovation Value Chain

For all companies that consider their Information Technology Department to be of strategic value, it is important to incorporate an innovation value chain into their software development lifecycles to enhance their teams' performance. One model is TDD (Test-Driven Development), which is a process that detects failures and improves the productivity and quality of the team’s work. Data were collected from a Financial Company with 3,500 employees to demonstrate that software projects that require more than 4,000 hours of development benefit from TDD if a clear knowledge conversion step occurs between the client and the developers.
Capital structure, product and banking market structure and performance

This thesis consists of three distinct essays on finance, market structure and performance. Paying particular attention to the degree of industry competition, the first essay investigates the relationship between capital structure and firm performance using panel data consisting of 257 South African firms over the period 1998 to 2009. The essay applies a novel measure of competition, the Boone indicator, to the leverage-performance relationship. The results suggest that financial leverage has a positive and significant effect on firm performance. It is also found that product market competition enhances the performance effect of leverage. The results are robust to alternative measures of competition and leverage. The second essay examines the extent of banking competition in African subregional markets. A dynamic version of the Panzar-Rosse model is adopted beside the static model to assess the overall extent of banking competition in each subregional banking market over the period 2002 to 2009. Consistent with other emerging economies, the results suggest that African banks generally demonstrate monopolistic competitive behaviour. Although the evidence suggests that the static Panzar-Rosse H-statistic is downward biased compared to the dynamic version, the competitive nature identified remains robust to alternative estimators. Paying particular attention to the degree of banking market concentration in developing countries, the third essay examines the effect of credit information sharing on bank lending. Using bank-level data from African countries over the period 2004 to 2009 and a dynamic two-step system generalised method of moments (GMM) estimation, it is found that credit information sharing increases bank lending. The degree of banking market concentration moderates the effect of credit information sharing on bank lending. The results are robust to controlling for possible interactions between credit information sharing and governance.
Basel Capital Adequacy Agreements and Bank Risk: Some Australian Evidence

This paper examines the impact of the Basel agreements (Basel I introduced in 1988, Basel I with market risk in 1998 and Basel II in 2008), on the level of systematic risk of the Australian big four banks. An augmented market model with three dummy variables is employed to capture any changes in systematic risk after each agreement was introduced. We contribute to the strand of literature on the effectiveness of the Basel agreements by providing evidence consistent with the view that the Basel agreements did not help to control bank risk, but instead increased it. In particular, we find that bank risk increased after Basel I and Basel II. Basel I with market risk partially achieved its goal with the Westpac Banking Corporation and Australia and New Zealand Banking Group Limited showing decreased risk while the National Australia Bank and Commonwealth Bank of Australia had no change.
"Resource Curse" Effect on Economic Growth in Western Region of China

Laggard economic development level coexists with wealthy natural resource endowment in western region of China, which is similar to the symptom of "resource curse". This paper suggests that "resource curse" effect is also applicable to explain the phenomenon at such a province level. Primary empirical analysis presents the possibility of suffering from the "curse" in the region, and then an econometric model and its long-term income effect is developed for testing the hypothesis and analyzing transmission channels through which "resource curse" effect functions. Through the panel data of twelve western provinces, we use feasible general least squares (FGLS) and select energy exploitation as a proxy of natural resource abundance to carry out a detailed empirical study. Econometric results reveal that our hypothesis is true. Abundant energy exploitation is not a favorable factor for economic growth in the long term, and it tends to impede economic growth through some indirect channels.
Investigation of the occurrence of torque tenovirus in malignant and potentially malignant disorders associated with human papillomavirus

In a previous pilot study, a significantly poorer outcome of laryngeal cancer was found in patients co‐infected with human papillomavirus (HPV) and genogroup 1 torque tenovirus (TTV). The present study aimed to collect data on the overall prevalence of TTVs on the prevalence of genogroup 1 TTV in two other malignancies associated with HPV, oral squamous cell cancer and cervical cancer, and in oral and cervical premalignant lesions (oral lichen planus, oral leukoplakia, cervical atypia). Oral samples from all patients were accompanied with a sample from the healthy mucosa. The overall prevalence of TTV was significantly higher both in oral squamous cell cancer and cervical cancer compared with other patient groups or with the respective controls. The prevalence of genogroup 1 TTV was significantly higher in lesions of oral squamous cell cancer and oral lichen planus, but not in lesions of oral leukoplakia (24.6%, 10.1%, and 4.5%, respectively), compared with the prevalence in the oral cavity of controls (1.4%). Co‐infection rates with genogroup 1 TTV and HPV were significantly higher in oral squamous cell cancer than in controls, oral lichen planus or oral leukoplakia patients (12.3%, 0.0%, 6.7%, and 4.5%, respectively). The prevalence of genogroup 1 TTV in all cervical samples were comparable. These data suggest that genogroup 1 TTV may be associated specifically with some head and neck mucosal disorders, but disproves a (co)carcinogenic role in oral cancer or cervical cancer as well as an association with HPV or with malignancies associated with HPV. J. Med. Virol. 81:1975–1981, 2009. © 2009 Wiley‐Liss, Inc.
Sensory Impairment in Obese Patients? Sensitivity and Pain Detection Thresholds for Electrical Stimulation After Surgery-induced Weight Loss, and Comparison With a Nonobese Population

Introduction:Obese patients have a high prevalence of painful musculoskeletal disorders that may decrease after massive weight loss. Pain thresholds may be different in obese participants. Objectives:To assess the sensitivity and pain detection thresholds, through the application of an electrical sensitivity, before and after massive weight loss, and to compare the thresholds obtained with those in a control population. Methods:The sensitivity and pain detection thresholds obtained in participants subjected to electrical stimulation were determined in 31 obese individuals (age: 40.3±10.5 y) before (body mass index: 45.7±6.8 kg/m2) and 6 months after a mean weight loss of 32 kg induced by gastric bypass. The results obtained were compared with those for 49 nonobese control participants (38.5±11.2 y; body mass index: 22.6±2.6 kg/m2). Body composition and metabolic biomarkers, such as leptin, adiponectin, insulin, and interleukin 6, were assessed and single-nucleotide polymorphisms of the mu opioid receptor [OPRM1 (c.118A>G) and COMT (p.Val158Met)] were genotyped in obese patients. Results:Sensitivity and pain detection thresholds (3.9±1.1; 11.6±6.0) were significantly higher in obese than in nonobese participants (3.1±1.1; 6.0±3.0), respectively (P<0.0001), and were not affected by drastic weight loss (mean change: 32 kg). Pain thresholds in obese participants were not correlated with any of the clinical and biological variables studied. The obese participants in the highest quartile for both sensitivity and pain detection thresholds were significantly older than those in the lowest quartile. Conclusions:Further studies are required to explore sensory dysfunction in obese individuals and to investigate the implications of this dysfunction for pain management.
Protective effects of curcumin and vitamin E against chlorpyrifos-induced lung oxidative damage

There are increasing concerns regarding the toxic effects of chlorpyrifos (CPF) on human health. Curcumin (CUR) is a yellow pigment isolated from turmeric ground rhizome of Curcuma longa Linn. , which has been identified as an antioxidant agent. This study was designed to examine the protective effect of CUR and vitamin E (Vit E) on CPF-induced lung toxicity. Rats were divided into seven groups: control, CPF (13.5 mg/kg, orally), CPF + CUR (100 and 300 mg/kg, respectively, orally), CPF + α-tocopherol (Vit E, 150 mg/kg, intraperitoneally), CPF and CUR (100 and 300 mg/kg, respectively) in combination with α-tocopherol. The regimens were administered once daily for 28 days. At the end of the treatment period, lungs were collected for evaluation of oxidative factors and histopathological parameters. CUR and Vit E led to a decrease in lipid peroxidation in the lungs of the CPF-injected animals (48% and 51%, respectively). Glutathione peroxidase inhibited by CPF (91.9 nmol/min/mg protein) was induced again by CUR and Vit E (167.1 and 171.8 nmol/min/mg protein). CUR and Vit E caused a significant induction of superoxide dismutase (103.4 U/mg protein). Catalase activity almost returned to normalcy in CPF-intoxicated rats subjected to CUR + Vit E treatment (p < 0.001). Lung sections from CPF-treated rats displayed histopathological damages, while coadministration of CUR and Vit E resulted in apparently normal morphology with a significant decrease in injuries (p < 0.05). Our findings revealed that coadministration of Vit E and CUR to CPF-treated animals prevents the oxidative damages in the lung tissues.
Pitavastatin Improves Cardiac Function and Survival in Association With Suppression of the Myocardial Endothelin System in a Rat Model of Hypertensive Heart Failure

Statin therapy may be associated with lower mortality in patients with heart failure, but the underlying mechanism of such an association is unknown. We have evaluated the effects of pitavastatin on cardiac function and survival in a rat model of hypertensive heart failure and investigated the molecular mechanism of the observed effects. Dahl salt-sensitive rats fed with high-salt diet from 7 weeks of age developed compensatory left ventricular hypertrophy at 12 weeks and heart failure at 19 weeks. Dahl salt-sensitive rats were treated with either vehicle or pitavastatin (0.3 mg/kg per day) from 7 or 12 weeks. Both early-onset and late-onset pitavastatin treatment reduced left ventricular fibrosis, improved cardiac function, and increased the survival rate apparent at 19 weeks. The increases in the expression levels of hypertrophic, profibrotic, and metalloproteinase genes as well as in gelatinase activities in the heart induced by the high-salt diet were suppressed by pitavastatin treatment. Furthermore, the level of cardiac endothelin-1 was increased in association with the development of heart failure in a manner sensitive to treatment with pitavastatin. Both early and late pitavastatin treatment thus improved cardiac function and survival, with modulation of extracellular matrix remodeling and endothelin-1 signaling possibly contributing to these beneficial effects.
An Introduction to Health

Part 1 The determinants of health: inequity in health lifestyle and health promotion planning health policy. Part 2 Planning health services: the history of the organization and financing of services methods of health service planning planning the health work-force planning primary health planning pharmaceuticals planning hospitals. Part 3 Health services financing: public health expenditure and the economic crisis private health expenditure compulsory health insurance. Part 4 Controlling costs and securing user-friendly services: methods of paying providers the efficient use of health resources facing up to the future.