Risk of second primary tumors following treatment of non-small cell lung cancer

Background. The rise in survival rates along with more detailed follow-up using sophisticated imaging studies among non-small lung cancer (NSCLC) patients has led to an increased risk of second primary tumors (SPT) among these cases. Population and hospital based studies of lung cancer patients treated between 1974 and 1996 have found an increasing risk over time for the development of all cancers following treatment of non-small cell lung cancer (NSCLC). During this time the primary modalities for treatment were surgery alone, radiation alone, surgery and post-operative radiation therapy, or combinations of chemotherapy and radiation (sequentially or concurrently). There is limited information in the literature about the impact of treatment modalities on the development of second primary tumors in these patients. ^ Purpose. To investigate the impact of treatment modalities on the risk of second primary tumors in patients receiving treatment with curative intent for non-metastatic (Stage I–III) non-small cell lung cancer (NSCLC). ^ Methods. The hospital records of 1,095 NSCLC patients who were diagnosed between 1980–2001 and received treatment with curative intent at M.D. Anderson Cancer Center with surgery alone, radiation alone (with a minimum total radiation dose of at least 45Gy), surgery and post-operative radiation therapy, radiation therapy in combination with chemotherapy or surgery in combination with chemotherapy and radiation were retrospectively reviewed. A second primary malignancy was be defined as any tumor histologically different from the initial cancer, or of another anatomic location, or a tumor of the same location and histology as the initial tumor having an interval between cancers of at least five years. Only primary tumors occurring after treatment for NSCLC will qualified as second primary tumors for this study. ^ Results. The incidence of second primary tumor was 3.3%/year and the rate increased over time following treatment. The type of NSCLC treatment was not found to have a striking effect upon SPT development. Increased rates were observed in the radiation only and chemotherapy plus radiation treatment groups; but, these increases did not exceed expected random variation. Higher radiation treatment dose, patient age and weight loss prior to index NSCLC treatment were associated with higher SPT development. ^

Second, do less harm: The state of states' medical error reporting programs

Statement of the problem and public health significance. Hospitals were designed to be a safe haven and respite from disease and illness. However, a large body of evidence points to preventable errors in hospitals as the eighth leading cause of death among Americans. Twelve percent of Americans, or over 33.8 million people, are hospitalized each year. This population represents a significant portion of at risk citizens exposed to hospital medical errors. Since the number of annual deaths due to hospital medical errors is estimated to exceed 44,000, the magnitude of this tragedy makes it a significant public health problem. ^ Specific aims. The specific aims of this study were threefold. First, this study aimed to analyze the state of the states' mandatory hospital medical error reporting six years after the release of the influential IOM report, "To Err is Human." The second aim was to identify barriers to reporting of medical errors by hospital personnel. The third aim was to identify hospital safety measures implemented to reduce medical errors and enhance patient safety. ^ Methods. A descriptive, longitudinal, retrospective design was used to address the first stated objective. The study data came from the twenty-one states with mandatory hospital reporting programs which report aggregate hospital error data that is accessible to the public by way of states' websites. The data analysis included calculations of expected number of medical errors for each state according to IOM rates. Where possible, a comparison was made between state reported data and the calculated IOM expected number of errors. A literature review was performed to achieve the second study aim, identifying barriers to reporting medical errors. The final aim was accomplished by telephone interviews of principal patient safety/quality officers from five Texas hospitals with more than 700 beds. ^ Results. The state medical error data suggests vast underreporting of hospital medical errors to the states. The telephone interviews suggest that hospitals are working at reducing medical errors and creating safer environments for patients. The literature review suggests the underreporting of medical errors at the state level stems from underreporting of errors at the delivery level. ^

The cost of publicly financed dental care in relation to community water fluoridation in Texas

Dental caries lead to children being less ready to learn and results in diminished productivity in the classroom. Tooth decay causes pain and infection, leading to impaired chewing, speech, and facial expression, in addition to a loss in self-esteem. There have been many studies supporting the safety and efficacy of community water fluoridation in reducing dental caries. Water fluoridation has been identified by the Centers for Disease Control and Prevention as one of 10 great public health achievements of the 20th century. The decline in the prevalence and severity of tooth decay in the United States during the past 60 years has been attributed largely to the increased use of fluoride; in particular, the widespread utilization of community water fluoridation. However, in the decades since fluoridation was first introduced, reductions in dental caries have declined, most likely due to the presence of other sources of fluoride. Questions have been raised regarding the need to continue to fluoridate community water supplies in the face of possible excessive exposure to fluoride. Nevertheless, dental caries continue to be a significant public health burden throughout the world, including the United States, especially among low-income and disadvantaged populations. Although many poor children receive their dental care through Medicaid, the percentage of Texas children with untreated dental caries continues to exceed the U.S. average and is well above Healthy People 2010 goals, even as state Medicaid expenditures continue to rise. The objective of this study is to determine the relationship between Medicaid dental expenditures and community water fluoridation levels in Texas counties. By examining this relationship, the cost-effectiveness of community water fluoridation in the Texas pediatric Medicaid beneficiary population, as measured by publicly financed dental care expenditures, may be ascertained.^

Selection bias and the cross-validation of regression models for prediction

Strategies are compared for the development of a linear regression model with stochastic (multivariate normal) regressor variables and the subsequent assessment of its predictive ability. Bias and mean squared error of four estimators of predictive performance are evaluated in simulated samples of 32 population correlation matrices. Models including all of the available predictors are compared with those obtained using selected subsets. The subset selection procedures investigated include two stopping rules, C$\sb{\rm p}$ and S$\sb{\rm p}$, each combined with an 'all possible subsets' or 'forward selection' of variables. The estimators of performance utilized include parametric (MSEP$\sb{\rm m}$) and non-parametric (PRESS) assessments in the entire sample, and two data splitting estimates restricted to a random or balanced (Snee's DUPLEX) 'validation' half sample. The simulations were performed as a designed experiment, with population correlation matrices representing a broad range of data structures.^ The techniques examined for subset selection do not generally result in improved predictions relative to the full model. Approaches using 'forward selection' result in slightly smaller prediction errors and less biased estimators of predictive accuracy than 'all possible subsets' approaches but no differences are detected between the performances of C$\sb{\rm p}$ and S$\sb{\rm p}$. In every case, prediction errors of models obtained by subset selection in either of the half splits exceed those obtained using all predictors and the entire sample.^ Only the random split estimator is conditionally (on $\\beta$) unbiased, however MSEP$\sb{\rm m}$ is unbiased on average and PRESS is nearly so in unselected (fixed form) models. When subset selection techniques are used, MSEP$\sb{\rm m}$ and PRESS always underestimate prediction errors, by as much as 27 percent (on average) in small samples. Despite their bias, the mean squared errors (MSE) of these estimators are at least 30 percent less than that of the unbiased random split estimator. The DUPLEX split estimator suffers from large MSE as well as bias, and seems of little value within the context of stochastic regressor variables.^ To maximize predictive accuracy while retaining a reliable estimate of that accuracy, it is recommended that the entire sample be used for model development, and a leave-one-out statistic (e.g. PRESS) be used for assessment. ^

Chronic stress promotes tumor growth through increased BDNF production and neo-innervation

Background: Activation of the sympathetic nervous system (SNS) in response to chronic biobehavioral stress results in high levels of catecholamines and persistent activation of adrenergic signaling, which promotes tumor growth and progression. However it is unknown how catecholamine levels within the tumor exceed systemic levels in circulation. I hypothesized that neo-innervation of tumors is required for stress-mediated effects on tumor growth. Results: First, I examined whether sympathetic nerves are present in human ovarian cancer samples as well as orthotopic ovarian cancer models. Immunohistochemical (IHC) staining for neurofilament revealed that catecholaminergic neurons are present within tumor tissue. In order to determine whether chronic stress affects the density of nerves in the tumor, I utilized an orthotopic mouse model of ovarian cancer that was exposed to daily restraint stress. IHC analysis revealed that nerve density in tumors increased by more than three-fold in stressed animals versus non-stressed controls. IHC analysis suggested that this results from both recruitment of existing neurons (axonogenesis) as well as new neuron formation (neurogenesis) within the tumor. To determine how tumors are recruiting nerve growth, I utilized a PCR array analysis of 84 nerve growth related genes and their receptors, which showed that stimulation of the SKOV3 ovarian cancer cell line with norepinephrine (NE) leads to increased expression of several neurotrophins, including brain-derived neurotrophic factor (BDNF). Neurite extension assays showed that media conditioned by ovarian cancer cell lines is capable of inducing neurite outgrowth in differentiated neuron-like PC12 cells, and NE treatment of cancer cells potentiates this effect. Norepinephrine-induced neurite extension was abolished after BDNF silencing by siRNA, suggesting that BDNF is critical to tumor cell-induced nerve growth. in vivo BDNF inhibition resulted in complete abrogation of stress-induced increases in tumor weight and nerve density, as well as downstream markers of stress. Discussion: These studies indicate that adrenergic signalling induced by chronic stress promotes neo-innervation in the tumor microenvironment. This results in a mutually beneficial relationship between the tumor cells and neurons. This work is crucial for providing a link between chronic stress and its effects on the tumor and its microenvironment. The data shown here aims to open new venues that can be used in development of therapies designed to block the stress effects on tumor growth.

The cost of insuring the uninsured in the U.S.

Objectives: This study included two overarching objectives. Through a systematic review of the literature published between 1990 and 2012, the first objective aimed to assess whether insuring the uninsured would result in higher costs compared to insuring the currently insured. Studies that quantified the actual costs associated with insuring the uninsured in the U.S. were included. Based upon 2009 data from the Medical Expenditure Panel Survey (MEPS), the second objective aimed to assess and compare the self-reported health of populations with four different insurance statuses. The second part of this study involved a secondary data analysis of both currently insured and currently uninsured individuals who participated in the MEPS in 2009. The null hypothesis was that there were no differences across the four categories of health insurance status for self-reported health status and healthcare service use. The alternative hypothesis was that were differences across the four categories of health insurance status for self-reported health status and healthcare service use. Methods: For the systematic review, three databases were searched using search terms to identify studies that actually quantified the cost of insuring the uninsured. Thirteen studies were selected, discussed, and summarized in tables. For the secondary data analysis of MEPS data, this study compared four categories of health insurance status: (1) currently uninsured persons who will become eligible for Medicaid under the Patient Protection and Affordable Care Act (PPACA) healthcare reforms in 2014; (2) currently uninsured persons who will be required to buy private insurance through the PPACA health insurance exchanges in 2014; (3) persons currently insured under Medicaid or SCHIP; and (4) persons currently insured with private insurance. The four categories were compared on the basis of demographic information, health status information, and health conditions with relatively high prevalence. Chi-square tests were run to determine if there were differences between the four groups in regard to health insurance status and health status. With some exceptions, the two currently insured groups had worse self-reported health status compared to the two currently uninsured groups. Results: The thirteen studies that met the inclusion criteria for the systematic review included: (1) three cost studies from 1993, 1995, and 1997; (2) four cost studies from 2001, 2003, and 2004; (3) one study of disabilities and one study of immigrants; (4) two state specific studies of uninsured status; and (5) two current studies of healthcare reform. Of the thirteen studies reviewed, four directly addressed the study question about whether insuring the uninsured was more or less expensive than insuring the currently insured. All four of the studies provided support for the study finding that the cost of insuring the uninsured would generally not be higher than insuring those already insured. One study indicated that the cost of insuring the uninsured would be less expensive than insuring the population currently covered by Medicaid, but more expensive to insure than the populations of those covered by employer-sponsored insurance and non-group private insurance. While the nine other studies included in the systematic review discussed the costs associated with insuring the uninsured population, they did not directly compare the costs of insuring the uninsured population with the costs associated with insuring the currently insured population. For the MEPS secondary data analysis, the results of the chi-square tests indicated that there were differences in the distribution of disease status by health insurance status. As anticipated, with some exceptions, the uninsured reported lower rates of disease and healthcare service use. However, for the variable attention deficit disorder, the uninsured reported higher disease rates than the two insured groups. Additionally, for the variables high blood pressure, high cholesterol, and joint pain, the currently insured under Medicaid or SCHIP group reported a lower rate of disease than the two currently insured groups. This result may be due to the lower mean age of the currently insured under Medicaid or SCHIP group. Conclusion: Based on this study, with some exceptions, the costs for insuring the uninsured should not exceed healthcare-related costs for insuring the currently uninsured. The results of the systematic review indicated that the U.S. is already paying some of the costs associated with insuring the uninsured. PPACA will expand health insurance coverage to millions of Americans who are currently uninsured, as the individual mandate and insurance market reforms will require. Because many of the currently uninsured are relatively healthy young persons, the costs associated with expanding insurance coverage to the uninsured are anticipated to be relatively modest. However, for the purposes of construing these results, it is important to note that once individuals obtain insurance, it is anticipated that they will use more healthcare services, which will increase costs. (Abstract shortened by UMI.)^

Weather Inputs to a Warning System for Sooty Blotch and Flyspeck of Apple

Sooty blotch and flyspeck (SBFS) is a mid- to late-season disease of apple. SBFS fungi show up as dark smudges and clusters of black dots on the fruit surface. Since blemished fruit are downgraded, crop losses can exceed 90 percent of the fresh market value.

Monitoreo de cadmio y plomo en los principales fungicidas cúpricos comercializados en Mendoza, Argentina

La aplicación de fungicidas ha tenido un incremento importante en los últimos períodos agrícolas, siendo los cúpricos los más utilizados en nuestro medio. Según el Instituto de Sanidad y Calidad Agropecuaria Mendoza (ISCAMEN), en el período 2004/2005 se han aplicado 2.500 toneladas de estos fungicidas: 44,80% sulfato de cobre; 54,24% oxicloruro de cobre y 0,96% de hidróxido de cobre, cantidades similares a las registradas en los últimos ciclos. Habiéndose detectado metales pesados en estos productos, se pretende determinar sus concentraciones en la mayoría de los cúpricos comercializados en Mendoza. Con tal objetivo se reunieron 53 muestras comerciales de fungicidas cúpricos (44 de sulfato y 9 de oxicloruro de cobre), que representan la mayoría de las marcas comercializadas. Sobre extractos ácidos se determinaron plomo y cadmio mediante espectrofotometría de absorción atómica de llama, contrastando con material de referencia altamente confiable. La legislación argentina sólo establece límites a los contenidos de plomo, el cual no puede superar el valor resultante de la fórmula: Límite de Pb mg.kg-1 = 5 x (% Cu del producto). Para el oxicloruro el valor límite es 275 mg.kg-1 y para el sulfato 125 mg.kg-1. Los datos fueron analizados estadísticamente con los siguientes resultados: para el oxicloruro la media fue de 207,17 mg.kg-1 y el 33,3% de las muestras superaron los valores permitidos para plomo. Para los sulfatos la media fue de 63,06 mg.kg-1 y ninguna de las muestras superó el límite máximo. La presencia de cadmio está representada por medias de 2,64 mg.kg-1 y 1,53 mg.kg-1 para oxicloruro y sulfato de cobre, respectivamente.

Metales pesados como indicador de impacto de un sistema ecológico fragmentado por usos de suelo, San Luis Potosí, México

La necesidad de estudiar la presencia de metales pesados en el suelo radica en su impacto como indicador de contaminación ambiental. Se determinó la presencia de Cu, Zn, Pb y Cd en suelos donde se distribuyen especies vegetales en un corredor ecológico. Entre los municipios de Soledad de Graciano Sánchez y San Luis Potosí (México) fueron establecidos 30 puntos distribuidos en cinco prácticas dominantes de usos de suelo: agropecuario, residencial rural, comercio y servicios, residencial urbano y minero. Los muestreos se realizaron en cuatro épocas durante 2009 y 2010 (verano, otoño, invierno y primavera). Se encontró un efecto significativo del uso del suelo en cuanto a los niveles de Cu (p = 0,000), Pb (p = 0,043) y Cd (p = 0,010). En el caso del Zn, el uso del suelo (p = 0,000) y la estación (p = 0,059) fueron significativos. El uso del suelo minero mostró las mayores concentraciones de metales y el agrícola las menores. Los niveles de los cuatro metales se encuentran en el rango marcado como alto por la EPA y por otras fuentes técnicas. En el caso de Pb y Cd no rebasan los estándares NOM-147- SEMARNAT-SSA1. Estos resultados reflejan el potencial indicativo del uso del suelo en la evaluación de la calidad ambiental, sin embargo, se requiere continuar con un monitoreo de metales pesados en la zona.

Current and potential water erosion estimation with RUSLE3D in Castellon province (Spain)

The purpose of this study was the estimation of current and potential water erosion rates in Castellon Province (Spain) using RUSLE3D (Revised Universal Soil Loss Equation-3D) model with Geographical Information System (GIS) support. RUSLE3D uses a new methodology for topographic factor estimation (LS factor) based on the impact of flow convergence allowing better assessment of sediment distribution detached by water erosion. In RUSLE3D equation, the effect that vegetation cover has on soil erosion rate is reflected by the C factor. Potential erosion indicates soil erosion rate without considering C factor in RUSLE3D equation. The results showed that 57% of estimated current erosion does not exceed 10 t/ha.year (low erosion). In the case of potential erosion rates, 5% of the area of Castellon Province does not exceed 10 t/ha.year but 55% exceed 200 t/ha.year. Based on these results, the current vegetation cover of Castellon Province is adequate but needs to be conserved to avoid an increase in the current soil erosion rates as shown by potential erosion rates.

Manganese nodules recovered by R/V Vityaz expedition

Uranium, radium, thorium and ionium were determined directly on seven concretions from three stations in the Indian Ocean, and on two concretions and a manganese-rich crust from two stations in the Pacific Ocean. The uranium content averages 3 to 5 gamma/g and the thorium content varies only slightly, but the Th/U ratio in the concretions is typically 2 to 5 in the Indian Ocean and 5 to 15.5 in the Pacific. The ionium content ranges from 1.0 x 10-9 to 3.6 10**-9 g/g in concretions from both oceans. Radium is more abundant in specimens from the Pacific Ocean (Ra = 3 - 12.7 x 10**-11 g/g) than from the Indian Ocean (1.5 - 5.2 x 10**-11 g/g). Analyses for Ca, Mn, Fe, Si, Ni, P, and ignition loss are also given. Radioactive equilibria between uranium, ionium, and radium are strongly disturbed throughout the concretions, and the RA/U and lo/U ratios generally exceed equilibrium ratios. Migration of radium from interior layers was established, so that neither determination of the ages of the concretions nor of their rates of growth can be considered reliable. The age of the concretions cannot exceed 800,000 years, and all grew within relatively short periods of time; there may have been "dormant" periods during growth. Estimates of growth rates are calculated from the radium and ionium contents; they show marked discordance.

Low-molecular-weight hydrocarbons in sediments at DSDP Sites 89-585 and 89-586

C2-C8 hydrocarbon concentrations (about 35 compounds identified, including saturated, aromatic, and olefinic compounds) from 38 shipboard sealed, deep-frozen core samples of Deep Sea Drilling Project Sites 585 (East Mariana Basin) and 586 (Ontong-Java Plateau) were determined by a gas stripping-thermovaporization method. Total concentrations, which represent the hydrocarbons dissolved in the pore water and adsorbed on the mineral surfaces of the sediment, vary from 20 to 630 ng/g of rock at Site 585 (sub-bottom depth range 332-868 m). Likewise, organic-carbon normalized yields range from 3*10**4 to 9*10**5 ng/g Corg, indicating that the organic matter is still in the initial, diagenetic evolutionary stage. The highest value (based on both rock weight and organic carbon) is measured in an extremely organic-carbon-poor sample of Lithologic Subunit VB (Core 585-30). In this unit (504-550 m) several samples with elevated organic-carbon contents and favorable kerogen quality including two thin "black-shale" layers deposited at the Cenomanian/Turonian boundary (not sampled for this study) were encountered. We conclude from a detailed comparison of light hydrocarbon compositions that the Core 585-30 sample is enriched in hydrocarbons of the C2-C8 molecular range, particularly in gas compounds, which probably migrated from nearby black-shale source layers. C2-C8 hydrocarbon yields in Site 586 samples (sub-bottom depth range 27-298 m) did not exceed 118 ng/g of dry sediment weight (average 56 ng/g), indicating the immaturity of these samples.

Physical properties and accumulation rates in Dronning Maud Land, Antarctica

The European Programme for Ice Coring in Antarctica includes a comprehensive pre-site survey on the inland ice plateau of Dronning Maud Land, Antarctica. The German glaciological programme during the 1997/98 field season was carried out along a 1200 km traverse on Amundsenisen and involved sampling the snow cover in pits and by shallow firn cores. This paper focuses on the accumulation studies. The cores were dated by dielectric-profiling and continuous-flow analysis. Distinct volcanogenic peaks and seasonal signals in the profiles served to establish a depth time-scale. The eruptions of Krakatoa, Tambora, an unknown volcano, Kuwae and El Chichon are well-documented in the ice. Variations of the accumulation rates over different times were inferred from the depth time-scales. A composite record of accumulation rates for the last 200 years was produced by stacking 12 annually resolved records. According to this, accumulation rates decreased in the 19th century and increased in the 20th century. The recent values are by no means extraordinary, as they do not exceed the values at the beginning of the 19th century. Variations in accumulation rates are most probably linked to temperature variations indicated in d18O records from Amundsenisen.

Chemical composition of DSDP cherts and associated host sediments

Chert and associated host sediments from Monterey Formation and Deep Sea Drilling Project (DSDP) sequences were analyzed in order to assess chemical behavior during diagenesis of biogenic sediments. The primary compositional contrast between chert and host sediment is a greater absolute SiO2 concentration in chert, often with final SiO2 >=98 wt%. This contrast in SiO2 (and Si/Al) potentially reflects precursor sediment heterogeneity, diagenetic chemical fractionation, or both. SiO2 concentrations and Si/Al ratios in chert are far greater than in modern siliceous oozes, however and often exceed values in acid-cleaned diatom tests. Compositional contrasts between chert and host sediment are also orders-of-magnitude greater than between multiple samples of the host sediment. Calculations based on the initial composition of adjacent host, observed porosity reductions from host to chert and a postulated influx of pure SiO2, construct a chert composition which is essentially identical to observed SiO2 values in chert. Thus, precursor heterogeneity does not seem to be the dominant factor influencing the current chert composition for the key elements of interest. In order to assess the extent of chemical fractionation during diagenesis, we approximate the precursor composition by analyzing host sediments adjacent to the chert. The SiO2 concentration contrast seems caused by biogenic SiO2 dissolution and transport from the local adjacent host sediment and subsequent SiO2 reprecipitation in the chert. Along with SiO2, other elements are often added (with respect to Al) to Monterey and DSDP chert during silicification, although absolute concentrations decrease. The two Monterey quartz chert nodules investigated, in contrast to the opal-CT and quartz chert lenses, formed primarily by extreme removal of carbonate and phosphate, thereby increasing relative SiO2 concentrations. DSDP chert formed by both carbonate/phosphate dissolution and SiO2 addition from the host. Manganese is fractionated during chert formation, resulting in MnO/Al2O3 ratios that no longer record the depositional signal of the precursor sediment. REE data indicate only subtle diagenetic fractionation across the rare earth series. Ce/Ce* values do not change significantly during diagenesis of either Monterey or DSDP chert. Eu/Eu* decreases slightly during formation of DSDP chert. Normative La/Yb is affected only minimally as well. During formation of one Monterey opal-CT chert lens, REE/Al ratios show subtle distribution changes at Gd and to a lesser extent near Nd and Ho. REE compositional contrasts between diagenetic states of siliceous sediment and chert are of a vastly smaller scale than has been noted between different depositional environments of marine sediment, indicating that the paleoenvironmental REE signature is not obscured by diagenetic overprinting.

Distribution of particulate matter and particulate organic carbon in waters of the Caspian Sea

Data on concentrations and distribution of particulate matter in the Caspian Sea obtained during surveys in 1981-1983 with use of modified filtering units have shown that over the major part of the sea concentration of particulate matter does dot exceed 1-2 mg/l. Only in the northern Caspian and in coastal regions concentrations correspond to values measured earlier. Total amount of particulate matter in the Caspian Sea is about of 90 million ton, 19.6% in the Northern Caspian, 28.1% in the Middle Caspian, and 52.3% in the Southern Caspian. Contents of carbon in particulate matter of the Central Caspian reach 30-40%, and over a significant part of the sea - 20%. A correlation has been found between areas of increased carbon contents in particulate matter and in bottom sediments. An important role of biofiltration in enrichment of particulates in organic matter has been noted. From data on carbon contents and an estimate of particulate matter input biogenic portion in particulate matter exceeds 50% for the whole sea.